Total Number Of High-intensity Transient Signals Research Articles

Abstract 16778: Effectiveness of Platelet Inhibition on Reducing High-Intensity Transient Signals to Cerebral Circulation During Tavi

Introduction: Despite the established dual antiplatelet treatment, embolic cerebrovascular events remain a major concern peri-operatively and following Transcatheter Aortic valve Implantation (TAVI). High Residual Platelet Reactivity (RPR) may contribute to platelet aggregation, propagating thrombosis on implanted materials. Therefore, we evaluated whether high RPR may predispose to an increased number of cerebrovascular emboli during the procedure. Methods: Consecutive patients who underwent transfemoral TAVI with Evolut™ R bioprosthesis were prospectively studied. Dual antiplatelet therapy with aspirin and a P2Y12 inhibitor was administered to all patients 24 hours prior to the procedure at loading dose. The number of detected High Intensity Transient Signals (HITS) was assessed using Rimed Digi-Lite™ Transcranial Doppler on both cerebral arteries during the following phases of the procedure; Phase 0: 30 minutes prior to procedure initiation, Phase I: between access site puncture and introduction of the delivery system, Phase II: during the implantation of the bioprosthesis, until the removal of the delivery system. Platelet inhibition was measured prior to the procedure and expressed in PRU, using the VerifyNow® assay and defined as high RPR if PRU≥208. Results: Out of 28 total patients (81±7 years, 18 males (64%)), 12 patients (81±9 years, 8 males (66.7%)) had PRU ≥208 (high RPR group), while 16 patients (81±5 years, 10 males (62.5%)) had PRU<208 (low RPR group). All device implantations were performed without balloon pre-dilation. Among the high RPR group, a statistically significant higher number of HITS was recorded compared to the low RPR group (707±149 vs. 530±152, p: 0.004). This was mainly driven by the number of HITS detected during Phase II, compared to the rest procedure stages (247±84 vs. 165±28, p:0.004). A statistical significant correlation of PRU with the total number of HITS was found (r2: 0.25, p: 0.006). Conclusions: High RPR after dual antiplatelet loading resulted in larger burden of embolic HITS during TAVI. This may has implications for future strategies for cerebral embolic protection.

Effect of Embolic Particles During Coronary Interventional Procedures on Regional Wall Motion in Patients With Stable Angina Pectoris

Microembolization during percutaneous coronary intervention (PCI) causes minor myocardial injury, and a Doppler guidewire can detect embolic particles as high-intensity transient signals (HITS). The present study investigated the effect of microembolization during PCI on regional wall motion using a Doppler guidewire and myocardial strain analysis. We performed PCI to the left anterior descending coronary artery in 25 patients (18 men and 7 women, 68 ± 8 years old) with stable angina pectoris. Coronary flow spectrums were obtained with a Doppler guidewire to count the total number of HITS throughout the PCI procedures. On the days before and after PCI, we recorded echocardiography and measured the longitudinal peak systolic strain, peak strain rate, and early diastolic strain rate in the left anterior descending territory using a 2-dimensional speckle tracking method. PCI was successfully performed, and 10 ± 6 HITS (range 0 to 22, median 9) were recognized during PCI. The echocardiographic study showed no visible wall motion abnormalities in the left anterior descending territory either after or before PCI. In cases in which the total number of HITS was ≥10, the peak systolic strain, peak strain rate, and early diastolic strain rate worsened on the day after PCI compared with those on the day before PCI (p <0.01). The rates of change in peak systolic strain and early diastolic strain rate, defined as the ratios of those parameters after PCI to those before PCI, had modest to strong inverse correlations with the total number of HITS (R(2) = 0.35 and R(2) = 0.46, respectively). In conclusion, periprocedural microembolization during PCI reduces subclinical cardiac function in patients with stable angina pectoris.

Deep Echo Attenuation without Calcification Increases the Risk of Periprocedural Myonecrosis after Elective Percutaneous Coronary Intervention in Patients with Coronary Artery Disease

To investigate the clinical factors, including intravascular ultrasound (IVUS) findings, associated with percutaneous coronary intervention (PCI)-related periprocedural myonecrosis (PM) in patients with stable coronary artery disease (CAD). The study included 46 patients (mean age 65±2 y, 37 men) with stable CAD who underwent elective PCI using IVUS and a Doppler flow guidewire. In addition to routine IVUS measurements, the presence of deep echo attenuation (DEA) without calcification was assessed. The sum of all high-intensity transient signals (HITS) after a balloon deflation procedure was calculated using a Doppler flow guidewire. PM was defined as an elevation in troponin T to >0.03 ng/mL 24-hour after PCI. Patients were divided into 2 groups on the basis of the presence or absence of PM. PM was identified in 17 patients (37%). Estimated glomerular filtration ratio was lower in the PM group (p=0.021). Target vessel distribution was different between the groups (p=0.004). Positive remodeling and DEA, as observed on IVUS, were more common in the PM group (p=0.03 and p<0.0001, respectively). The total number of HITS was higher in the PM group (p=0.003). Logistic regression analysis demonstrated that the presence of DEA (p=0.003) was the sole factor associated with the occurrence of PM. These results demonstrated that DEA is an important factor associated with PM in patients who underwent an elective PCI. Therefore, IVUS to determine the presence of DEA should be performed before PCI.

Cerebral Embolic Exposure During Transfemoral and Transapical Transcatheter Aortic Valve Replacement

To characterize the cerebral embolic exposure during transfemoral (TF) and transapical (TA) TAVR. To detect cerebral embolic events during TAVR, intraoperative neuromonitoring using transcranial Doppler (TCD) was utilized in 28 patients (Edwards SAPIEN valve TF n = 18, TA n = 10). High intensity transient signals (HITS) reflective of embolic events were recorded. The mean age was 83.4 ± 7.4 years. The Society of Thoracic Surgeons predicted risk of mortality score was 11.7 ± 2.9. The total number of HITS during TAVR was not significantly different between the TF and the TA groups, respectively (375 ± 301, 440 ± 283, p = 0.58). The highest number of HITS occurred during wire manipulation in the arch and valve insertion (TF, 80 ± 110, 107 ± 81; TA, 120 ± 80, 92 ± 80). In the TF group only, severe arch calcification was associated with significantly higher number of HITS both in total number of HITS (Grade I/II, 278 ± 71; Grade III/IV, 568 ± 479, p = 0.05) and during wire manipulation in the arch and valve insertion (Grade I/II, 140 ± 46, Grade III/IV 294 ± 239, p = 0.04). Highest cerebral embolic exposure occurred during wire manipulation in the arch and valve insertion in both the TF and TA groups. Arch calcification appears to be associated with increased embolic risk, specifically in the TF approach. Understanding of the mechanism of cerebral embolism is needed for future strategies of cerebral protection during TAVR.

Cerebral Emboli Generation during Off-Pump Coronary Artery Bypass Grafting with a Clampless Device versus Partial Clamping of the Ascending Aorta

: It is not known whether use of a clampless facilitating device during proximal graft anastamosis decreases intraoperative cerebral emboli in patients with mild atherosclerotic ascending aorta (AAA) having off-pump coronary artery bypass. : After intraoperative epiaortic ultrasound showed no more than mild (grade I-II) atherosclerotic ascending aorta, 20 patients were randomized to receive either partial clamping (PC, n = 10) or the HEARTSTRING clampless device (HS, n = 9) for proximal graft construction on the ascending aorta. Continuous transcranial Doppler monitoring, with capability to discern gaseous from solid particulates, was used intraoperatively to monitor high-intensity transient signals (HITS) in the middle cerebral arteries. Postoperative diffusion-weighted brain magnetic resonance imaging documented old and new ischemic brain lesions. : There were no significant differences between the groups in the number of proximals (P = 0.14), distals (P = 0.4), or intraoperative cell saver transfusions (P = 0.69). The total number of HITS was not significantly different between the PC and HS groups (P = 0.2). However, the number of solid HITS was significantly lower in the HS than in the PC group (2.7 ± 2.6 versus 14.0 ± 8.1; P < 0.001). The number of gaseous emboli in the HS group was fourfold greater when a mister-blower rather than a suction device was used to clear blood away from the HS site. Postoperatively, there were no deaths, myocardial infarctions, or clinical strokes observed in either group. Diffusion-weighted cerebral magnetic resonance imaging revealed no statistical difference between groups for new infarct lesions. : Use of the HS device during off-pump coronary artery bypass was associated with significantly fewer intraoperative solid emboli in the middle cerebral artery than PC of the ascending aorta.

Clinical Implications of Distal Embolization During Coronary Interventional Procedures in Patients With Acute Myocardial Infarction: Quantitative Study With Doppler Guidewire

This study sought to investigate the timing and amount of embolic particles generation during the percutaneous coronary intervention (PCI) procedure and studied the relationship between embolic burden and coronary blood flow and myocardial damage. Distal embolization is a major complication of PCI. The Doppler guidewire (DGW) can detect the embolic particles as high-intensity transient signals (HITS) during the PCI procedure. We prospectively studied 37 patients with acute myocardial infarction (MI). Under monitoring with the DGW, we performed first and second balloon angioplasty, followed by stenting and post-high-pressure dilatation. Left ventricular ejection fraction (LVEF) (%) and regional wall motion (RWM) (standard deviation/chord) were measured on days 1 and 22. The HITS were detected in 35 of 37 patients. The number of HITS was the greatest after stenting (16 +/- 18) followed by first balloon inflation (5 +/- 4). There was a significant correlation between the total number of HITS and the corrected Thrombolysis In Myocardial Infarction frame count (r = 0.52, p = 0.003) and a significant weak inverse correlation between the total number of HITS and changes in LVEF and RWM (r = 0.37, p = 0.03 and r = 0.35, p = 0.04, respectively). Distal embolization is common during PCI in patients with acute MI, and the majority of HITS were observed after stenting. An increase in the total number of HITS is associated with reduced coronary blood flow, and is weakly associated with poor recovery of left ventricular function.

Detection and quantification of embolic particles during percutaneous coronary intervention to stable plaque: It correlates to coronary flow dynamics and myocardial damage

We detected embolic particles liberated from plaque during percutaneous coronary intervention (PCI) as high-intensity transient signals (HITS) with a Doppler guidewire and studied their impact on coronary flow dynamics and the myocardium in patients with stable angina pectoris. These embolic particles during PCI may cause myocardial injury. However, this was difficult to confirm because it was impossible to detect embolic particles. We performed balloon angioplasty followed by stenting in 31 patients while monitoring coronary flow velocity. After PCI, we measured average peak velocity at baseline and after infusion of adenosine 5'-triphosphate to calculate coronary flow velocity reserve (CFVR) and coronary resistance index (CRI). In patients with PCI to the left coronary artery (n = 21), we calculated relative CFVR as the ratio of CFVR in the target vessel to that in the reference vessel. We measured cardiac troponin T (cTnT) the day after PCI. HITS were detected in 27 (87%) of 31 patients and the majority were observed after stenting. The total number of HITS was correlated with CRI (r = 0.36, P = 0.049) or relative CFVR (r = 0.65, P = 0.0036) but not with CFVR (r = 0.048, P = 0.82). Thirteen patients showed elevated cTnT (range, 0.05-0.31 ng/ml) and the total number of HITS was greater in those with elevated cTnT than in those without elevated cTnT (24 +/- 9 vs. 10 +/- 7, P = 0.0007). Embolic particles are frequently observed during PCI to stable plaque and the majority are liberated after stenting. There appears to be a quantitative relationship between amounts of HITS and coronary microvessel dysfunction and minor myocardial injury.

Association between large aortic arch atheromas and high-intensity transient signals in elderly stroke patients.

Aortic arch atheromas (AAs) have been shown to be a risk factor for ischemic stroke (IS) in the elderly because of their potential for cerebral embolization. However, the association between AAs and the presence of cerebral microemboli has not been clearly established. The aim of this study was to determine whether large AAs are associated with an increased frequency of high-intensity transient signals (HITS) in elderly patients with IS. We performed bitemporal simultaneous HITS monitoring of both middle cerebral arteries in 62 consecutive elderly patients with acute IS (mean age 72.5+/-8.8 years, 65% men). In 16 patients, one or both temporal windows were inadequate; therefore, the analysis of HITS was performed in the remaining 46 patients. All patients underwent omniplane transesophageal echocardiography (TEE), and they had no significant extracranial or intracranial artery disease and no cardiac prosthetic valves. Large AA was defined as > or = 4 mm in thickness. Complex AA was defined as ulcerated or mobile, regardless of plaque thickness. HITS monitoring was performed within 24 hours of TEE and analyzed by an experienced neurologist-sonographer blinded to TEE findings. A 9-dB threshold was chosen to discriminate HITS from background Doppler signal. The HITS counts in the left and in the right middle cerebral arteries were added and reported as a total number of HITS in 30 minutes. HITS were detected in 14 (78%) of 18 patients with large AAs versus 8 (29%) of 28 patients with no or small AAs (odds ratio [OR] 8.8, 95% CI 2.2 to 34.8; P=0. 001). The association was also present in 27 patients with no other cardiac embolic sources, such as atrial fibrillation, patent foramen ovale, spontaneous echo contrast, and thrombus (7 of 10 patients with large AAs versus 3 of 17 patients with small or no AA; OR 10.9, 95% CI 1.7 to 68.5; P=0.013). Complex AAs were associated with a higher frequency of HITS than were noncomplex AAs (6 of 6 patients with complex AAs versus 15 of 39 patients with noncomplex AAs; OR 2. 6, 95% CI 1.7 to 3.9; P=0.005). HITS are significantly associated with large AAs in elderly stroke patients. This observation may support the causal role of large AAs in IS.

人工心肺におけるＴＣＤによるＨｉｇｈ‐ｉｎｔｅｎｓｉｔｙ Ｔｒａｎｓｉｅｎｔ Ｓｉｇｎａｌｓ（ＨＩＴＳ）の周波数分析の臨床的意義について

Purpose: High-intensity transient signals (HITS) are commonly detected during cardiopulmonary bypass (CPB) . However, the clinical significance of HITS during CPB is still controversial. Micro-bubbles are reported to produce HITS of more than 400-500 Hz. We attempted to elucidate the incidence of HITS exceeding 400 Hz during CPB. Methods: The subjects were 6 patients who underwent open heart surgery using CPB. HITS were detected by TC2020, PIONEER (Nicolet /EME) with a 2.0-MHz pulsed Doppler probe at the middle cerebral artery. Transesophageal echocardiography (TEE) was undertaken during the operation. Results: The total number of HITS during CPB was 1707±1392 (n=6) . Of the total HITS, 88.1±6.8% had a frequency of more than 400 Hz. On the other hand, HITS of less than 400 Hz were frequently detected at aortic cannulation, aortic decannulation and aortic cross-clamping. HITS of more than 400 Hz were detected in cases showing cardiac or aortic micro-bubbles in TEE. Conclusion: The present findings suggest that the majority of HITS during CPB reflect micro-bubbles, and that aortic manipulation may be related to the formation of solid micro-emboli. HITS frequency analysis may be useful for differentiating between micro-bubbles and solid micro-emboli formed during CPB.

Transcranial Doppler monitoring of cerebral embolism in atrial fibrillation and prosthetic valves. Clinical correlations

Transcranial Doppler (TCD) monitoring of the middle cerebral artery (MCA) permits the detection of high intensity transient signals (HITS), which are believed to represent microemboli. Non-valvular atrial fibrillation (NVAF) and prosthetic heart valves (PV) are important risk factors for embolic stroke. We evaluated both the prevalence and the frequency of microemboli in these high risk groups and the correlation with previous stroke. Sixty-six patients were monitored for 30 min on both MCAs sequentially. Twenty healthy subjects were studied as well. The total number of HITS recorded on both sides, expressed as HITS/h, was used for comparison. In NVAF patients (n = 24) the prevalence of HITS was 25%, in PV (n = 16) 62% and in those patients in whom PV coexisted with atrial fibrillation (PVAF) (n = 26), it was 42%. None in the control group showed HITS. HITS occurred significantly more frequently in PVAF (12.3/h) than in both NVAF (1.4/h, p = 0.007) and PV (2.7/h, p = 0.011), whereas there was no difference between PV and NVAF. The prevalence of HITS was not statistically different in patients with and without previous stroke, but among HITS positive patients those with previous stroke had a significantly higher HITS frequency (18.9 vs 8.5/h, p = 0.04). In conclusion, in patients with cardiac embolic sources the frequency of HITS increases from the classes with the lower (NVAF, PV) to the class with the highest (PVAF) risk factor. Patients with previous stroke have more HITS than asymptomatic ones. Therefore, embolus detection monitoring seems a promising tool in the assessment of the individual stroke risk in patients with cardiac embolic sources.