Number Of High-intensity Transient Signals Research Articles

A Scoping Review of Cerebral Doppler Arterial Waveforms in Infants.

Cerebral Doppler ultrasound has been an important tool in pediatric diagnostics and prognostics for decades. Although the Doppler spectrum can provide detailed information on cerebral perfusion, the measured spectrum is often reduced to simple numerical parameters. To help pediatric clinicians recognize the visual characteristics of disease-associated Doppler spectra and identify possible areas for future research, a scoping review of primary studies on cerebral Doppler arterial waveforms in infants was performed. A systematic search in three online bibliographic databases yielded 4898 unique records. Among these, 179 studies included cerebral Doppler spectra for at least five infants below 1 y of age. The studies describe variations in the cerebral waveforms related to physiological changes (43%), pathology (62%) and medical interventions (40%). Characteristics were typically reported as resistance index (64%), peak systolic velocity (43%) or end-diastolic velocity (39%). Most studies focused on the anterior (59%) and middle (42%) cerebral arteries. Our review highlights the need for a more standardized terminology to describe cerebral velocity waveforms and for precise definitions of Doppler parameters. We provide a list of reporting variables that may facilitate unambiguous reports. Future studies may gain from combining multiple Doppler parameters to use more of the information encoded in the Doppler spectrum, investigating the full spectrum itself and using the possibilities for long-term monitoring with Doppler ultrasound.

Detection of Cerebral High-Intensity Transient Signals by NeoDoppler during Cardiac Catheterization and Cardiac Surgery in Infants.

There is a risk of gaseous and solid micro-embolus formation during transcatheter cardiac interventions and surgery in children with congenital heart disease (CHD). Our aim was to study the burden of high-intensity transient signals (HITS) during these procedures in infants. We used a novel color M-mode Doppler (CMD) technique by NeoDoppler, a non-invasive ultrasound system based on plane wave transmissions for transfontanellar continuous monitoring of cerebral blood flow in infants. The system displays CMD with 24 sample volumes and a Doppler spectrogram. Infants with CHD undergoing transcatheter interventions (n=15) and surgery (n=13) were included. HITS were manually detected based on an "embolic signature" in the CMD with corresponding intensity increase in the Doppler spectrogram. Embolus-to-blood ratio (EBR) defined HITS size. A total of 1169 HITS with a median EBR of 9.74 dB (interquartile range [IQR]: 5.10-15.80 dB) were detected. The median number of HITS in the surgery group was 45 (IQR: 11-150), while in the transcatheter group the median number was 12 (IQR: 7-24). During cardiac surgery, the highest number of HITS per hour was seen from initiation of cardiopulmonary bypass to aortic X-clamp. In this study we detected frequent HITS and determined the feasibility of using NeoDoppler monitoring for HITS detection.

Transcranial Doppler for stratification of high-risk morphology of patent foramen ovale in patients with cryptogenic stroke.

Microbubble testing using transcranial Doppler (TCD) is an important screening tool for diagnosing paradoxical cerebral embolism with high-risk PFO. However, little is known about the association between the microbubble test by TCD and the features of high-risk PFO evaluated by transesophageal echocardiography (TEE). We studied 101 consecutive patients at Showa University, from April 2019 to October 2020, who underwent both TCD and TEE with a sufficient Valsalva maneuver and who were strongly suspected by neurologists as cryptogenic stroke. According to the appearance of microbubbles as high-intensity transient signals (HITS), the TCD grade was stratified into three categories based on the criteria (A: none, no HITS, B: small; 1-10 HITS, and C: large; > 10 HITS, or an uncountable number of HITS). Among patients with RLS through the PFO in TEE, high-risk morphological features of PFO for cerebral embolism were evaluated as follows: (1) tunnel height, (2) tunnel length, (3) total excursion distance of the atrial septum into the right and left atrium, (4) existence of Eustachian valve or Chiari network, (5) angle of PFO from the inferior vena cava, and (6) large shunt (20 or more microbubbles). Of 101 patients (TCD grade; Group A = 49, Group B = 26, Group C = 26), RLS through PFO was detected in 37 patients (grade A = 8, grade B = 6, grade C = 23) by TEE. Among PFO-positive patients, tunnel height, length, total excursion distance into the right and left atria, angle of PFO from the inferior vena cava, and frequency of large shunt in TEE were significantly larger in grade C than in grade A and B (p < 0.05). Additionally, grade C patients had significantly more forms of high-risk PFOs than those in grades A and B when the six features of high-risk PFO were compared. A multivariate logistic regression demonstrated that the tunnel length of PFO and the presence of large shunt in TEE were independently associated with large HITS in TCD (odds ratio: 1.18 and 49.5, 95% confidence interval 1.043-1.337 and 10.05-244.3, p = 0.0086 and p < 0.0001, respectively). In conclusion, the existence of a large HITS detected by TCD may have a screening advantage in predicting the high-risk morphologies of PFO that can cause paradoxical cerebral embolism.

Comparison of Ticagrelor Versus Clopidogrel on Cerebrovascular Microembolic Events and Platelet Inhibition during Transcatheter Aortic Valve Implantation

The impact of the antiplatelet regimen and the extent of associated platelet inhibition on cerebrovascular microembolic events during transcatheter aortic valve implantation (TAVI) are unknown. Our aim was to evaluate the effects of ticagrelor versus clopidogrel and of platelet inhibition on the number of cerebrovascular microembolic events in patients undergoing TAVI. Patients scheduled for TAVI were randomized previous to the procedure to either aspirin and ticagrelor or to aspirin and clopidogrel. Platelet inhibition was expressed in P2Y12 reaction units (PRU) and percentage of inhibition. High intensity transient signals (HITS) were assessed with transcranial Doppler (TCD). Safety outcomes were recorded according to the VARC-2 definitions. Among 90 patients randomized, 6 had an inadequate TCD signal. The total number of procedural HITS was lower in the ticagrelor group (416.5 [324.8, 484.2]) (42 patients) than in the clopidogrel group (723.5 [471.5, 875.0]) (42 patients), p <0.001. After adjusting for the duration of the procedure, diabetes, extra-cardiac arteriopathy, BMI, hypertension, aortic valve calcium content, procedural ACT, and pre-implantation balloon valvuloplasty, patients on ticagrelor had on average 256.8 (95% CI: [-335.7, -176.5]) fewer total procedural HITS than patients on clopidogrel. Platelet inhibition was greater with ticagrelor 26 [10, 74.5] PRU than with clopidogrel 207.5 (120 to 236.2) PRU, p <0.001, and correlated significantly with procedural HITS (r=0.5, p <0.05). In conclusion, ticagrelor resulted in fewer procedural HITS, compared with clopidogrel, in patients undergoing TAVI, while achieving greater platelet inhibition.

Correlation of platelet inhibition and cerebral thromboembolic events, as expressed with number of high-intensity transient signals,during Transcatheter Aortic valve Implantation

Abstract Background It has been shown that high Residual Platelet Reactivity (RPR) may contribute to platelet aggregation which propagates thrombosis on implanted materials. Therefore, we evaluated whether high RPR may predispose to an increased number of cerebrovascular emboli during Transcatheter Aortic valve Implantation (TAVI). Methods Consecutive patients who underwent transfemoral TAVI with a self-expandable valve were prospectively studied. A loading dose of P2Y12 inhibitor 24 hours preprocedurally was given. Additionally, aspirin was started one week prior to procedure in all patients. Platelet inhibition was assessed with P2Y12 reaction units (PRU) (Verify Now assay) as well as percentage of inhibition 30 minutes prior to procedure initiation. The number of High intensity transient signals (HITS) was assessed with Rimed Digi-Lite™ transcranial Doppler, setting a threshold for detection of HITS at 3dB, continuously, on both middle cerebral arteries during the whole procedure. Two observers reviewed offline the number of HITS. Results In total, 84 patients underwent TAVI (53 males, mean age=81.9yrs old ±8,98). Mean baseline PRU and percentage of platelet inhibition was 258,24±43,03 (156–376) and 48,51%±40.05 (0–100%) respectively. In the treated patients the mean absolute total number of HITS and the number of HITS per minute recorded, was 566,63±272,32, (136–1432) and 6.7/min±3.3 (2.09–13.24) respectively. Significant positive correlation was found between baseline PRU levels and number of total HITS (r=0.261, p=0.017), (Figure 1). Multivariate regression analysis revealed that PRU was independent prognostic factor of total HITS (β=0.708, p=0.06), In order to clarify the predictive role of platelet inhibition in the total number of recorded HITS a ROC analysis was performed, obtaining an area under the curve of 0.646 (95% CI 0.518 to 0.773, p=0.047). PRU-levels≥169 were shown to predict number of HITS at the upper quartile with 76% sensitivity and 65% specificity. Conclusion High RPR after dual antiplatelet loading with a P2Y12 inhibitor and aspirin, resulted in larger burden of embolic HITS during TAVI procedure. A cut off point of 169 PRU units with 76% sensitivity and 65% specificity predicted detection of HITS at the higher quartile. PRU-HITS Correlation Funding Acknowledgement Type of funding source: None

Most High-Intensity Transient Signals Are Not Associated With Specific Surgical Maneuvers.

Mortality after congenital heart defect surgery has dropped dramatically in the last few decades. Current research on long-term outcomes has focused on preventing secondary neurological sequelae, for which embolic burden is suspected. In children, little is known of the correlation between specific surgical maneuvers and embolic burden. Transcranial Doppler ultrasound is highly useful for detecting emboli but has not been widely used with infants and children. Bilateral middle cerebral artery blood flow was continuously monitored from sternal incision to chest closure in 20 infants undergoing congenital heart defect repair or palliative surgery. Embolus counts for specific maneuvers were recorded using widely accepted criteria for identifying emboli via high-intensity transient signals (HITS). An average of only 13% of all HITS detected during an operation were correlated with any of the surgical maneuvers of interest. The highest mean number of HITS associated with a specific maneuver occurred during cross-clamp removal. Cross-clamp placement also had elevated HITS counts that significantly differed from other maneuvers. In this study of infants undergoing cardiac surgery with cardiopulmonary bypass, the great majority of HITS detected are not definitively associated with a specific subset of surgical maneuvers. Among the measured maneuvers, removal of the aortic cross-clamp was associated with the greatest occurrence of HITS. Future recommended research efforts include identifying and confirming other sources for emboli and longitudinal outcome studies to determine if limiting embolic burden affects long-term neurological outcomes.

Assessing Cerebrovascular Hemodynamics Using Transcranial Doppler in Patients with Mechanical Circulatory Support Devices.

Mechanical circulatory support (MCS) devices are commonly used in heart failure patients. These devices carry risk for presumably embolic and additionally hemorrhagic stroke. Alterations in blood flow play a key role in stroke pathophysiology, and we aimed to learn more about hemodynamic compromise. In this study, we used transcranial Doppler (TCD) ultrasound to define hemodynamics of commonly used nonpulsatile MCS devices, as well as pulsatile devices, with special attention to the total artificial heart (TAH). From 2/2013 through 12/2016, we prospectively enrolled patients with MCS who underwent TCD imaging. We analyzed TCD parameters, including peak systolic velocity, end-diastolic velocity, pulsatility indices (PIs), and number of high-intensity transient signals. Waveform morphologies were compared between various MCS devices. We performed 132 TCD studies in 86 MCS patients. Waveforms in patients supported by venoarterial-extracorporeal membrane oxygenation demonstrated continuous flow without clear systolic peaks with an average (±SD) PI of .43 (±.2). PIs were low in patients with continuous-flow left ventricular assist devices with a mean PI of .32 (±.13). Impella patients had morphologically distinct pulsatile waveforms and a higher mean PI of .65 (±.24). In intra-arterial balloon pump patients, mean PI was 1.01 (±.16) and diastolic upstrokes were pronounced. In TAH patients, mean middle cerebral artery velocity of 79.69 (±32.33) cm/seconds and PI of .74 (±.14) approached normal values. TCD can detect characteristic waveforms in patients supported by various MCS devices. These device-specific TCD patterns are recognizable and reproducible.

PC058. A Novel Aortic Arch Flow Model to Test the Efficacy of Cerebral Embolic Protection Devices Using Transcranial Doppler

Clinically apparent stroke occurs in up to 6% of patients undergoing thoracic endovascular aortic repair and up to 4% of patients undergoing carotid artery stenting. However, clinically silent cerebral infarction is seen on postoperative diffusion-weighted magnetic resonance imaging in >60% of patients undergoing thoracic endovascular aortic repair and leads to an increased risk of future stroke and dementia. Embolic protection devices are associated with lower stroke rates and smaller volume of ischemic lesions on diffusion-weighted magnetic resonance imaging. We created a novel aortic arch flow model and tested the efficacy of the FilterWire EZ (Boston Scientific, Marlborough, Mass) using transcranial Doppler ultrasound. By employing a three-dimensional printed aortic arch, we created a closed-circuit flow model that can simulate continuous and pulsatile blood flow (Fig, A-C). Dissolved cornstarch particles simulate circulating red and white blood cells, which typically range in size from 6 to 15 μm, to provide a background signal for detection of solid and gaseous emboli on transcranial Doppler ultrasound (Fig, D and E). A 38-μm filter placed in series ensures that injected microparticles do not recirculate and the circuit is deaired. We then prepared and deployed a FilterWire EZ, a uniform 110-μm pore filter commonly used during carotid artery stenting, according to the instructions for use. Embozene Microspheres (Boston Scientific) of known sizes were diluted in saline to 1 mL of particles per 10 mL of solution. High-intensity transient signals (HITS) were recorded during filter deployment, injection of 1 mL of solution, and filter retrieval. This process was repeated for Embozene particles of 75-, 100-, 250-, and 400-μm diameters. Each continuous 1-second shower of emboli was counted as 15 HITS. Despite preparation of the FilterWire EZ according to instructions for use, there were on average 41 ± 7 (range, 31-49) HITS during filter deployment and 7 ± 7 (range, 1-17) HITS during filter retrieval. Average number of HITS during injection was 87 ± 130 (range, 4-315), and more HITS were seen distal to the filter on injection of microparticles that were smaller than the 110-μm pore size (142 ± 150 vs 5 ± 1; P = .31). Mean velocity (cm/s) of the fluid decreased by 18% ± 2% after filter deployment and 50% ± 34% during injection of microparticles and returned to baseline after filter retrieval. We created and validated a novel aortic arch flow model. HITS were seen during all stages of the procedure using the FilterWire EZ. This model can be used to test the efficacy of all available embolic protection devices and methods of deairing stent grafts.

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&lt;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.

Operative strategies to reduce cerebral embolic events during on- and off-pump coronary artery bypass surgery: A stratified, prospective randomized trial

ObjectiveTo determine the impact of different aortic clamping strategies on the incidence of cerebral embolic events during coronary artery bypass grafting (CABG). MethodsBetween 2012 and 2015, 142 patients with low-grade aortic disease (epiaortic ultrasound grade I/II) undergoing primary isolated CABG were studied. Those undergoing off-pump CABG were randomized to a partial clamp (n = 36) or clampless facilitating device (CFD; n = 36) strategy. Those undergoing on-pump CABG were randomized to a single-clamp (n = 34) or double-clamp (n = 36) strategy. Transcranial Doppler ultrasonography (TCD) was performed to identify high-intensity transient signals (HITS) in the middle cerebral arteries during periods of aortic manipulation. Neurocognitive testing was performed at baseline and 30-days postoperatively. The primary endpoint was total number of HITS detected by TCD. Groups were compared using the Mann–Whitney U test. ResultsIn the off-pump group, the median number of total HITS were higher in the CFD subgroup (30.0; interquartile range [IQR], 22-43) compared with the partial clamp subgroup (7.0; IQR, 0-16; P < .0001). In the CFD subgroup, the median number of total HITS was significantly lower for patients with 1 CFD compared with patients with >1 CFD (12.5 [IQR, 4-19] vs 36.0 [IQR, 25-47]; P = .001). In the on-pump group, the median number of total HITS was 10.0 (IQR, 3-17) in the single-clamp group, compared with 16.0 (IQR, 4-49) in the double-clamp group (P = .10). There were no differences in neurocognitive outcomes across the groups. ConclusionsFor patients with low-grade aortic disease, the use of CFDs was associated with an increased rate of cerebral embolic events compared with partial clamping during off-pump CABG. A single-clamp strategy during on-pump CABG did not significantly reduce embolic events compared with a double-clamp strategy.

Abstract WMP66: Cerebrovascular Hemodynamics of Mechanical Circulatory Support Device Patients

Background: Multiple types of mechanical circulatory support (MCS) devices are commonly used in heart failure patients. These devices carry risk for neurologic complications, specifically cardioembolic stroke. Alterations in blood flow play a role in the pathophysiology, however there is limited data regarding cerebrovascular hemodynamics in MCS patients. We used transcranial Doppler (TCD) to define hemodynamics of commonly used MCS devices. Methods: We retrospectively examined charts from 2/2013 through 6/2016 for patients with MCS who underwent TCD, and obtained the following: peak systolic,end-diastolic velocities, mean flow velocities, pulsatility indices (PI) and number of high-intensity transient signals (HITS). Waveform morphologies were compared between devices. Results: Of 1,796 TCDs studies screened, 62 TCD studies were from 32 MCS patients. Of these, 21 were on extracorporeal membrane oxygenation (ECMO), 15 had a left ventricular assist device (LVAD), 18 had total artificial heart (TAH), and 2 had intra-aortic balloon pumps (IABP). Waveforms in patients supported by ECMO demonstrated continuous flow without clear systolic peaks. The averaged mean MCA velocity was 57.57 (SD= 21.00) cm/sec and mean PI is 0.35 (0.17). LVAD averaged mean MCA velocity was 57.57 (14.38) cm/sec and mean PI of 0.45 (0.28). PIs were low in patients with continuous-flow LVADs. Impella patients had morphologically distinct pulsatile waveforms compared to other types of VADs. IABP had averaged mean velocity of 56.21 (14.78) cm/sec and mean PI of 0.77 (0.15). These waveforms demonstrated pronounced diastolic upstrokes not present in other devices. In TAH patients, mean MCA velocity was 73.69 (33.00) cm/sec and PI of 0.86 (0.40). Emboli detection was performed in 46 studies, and HITS were detected in 29 (63%). Of these 15 (51%) were administered 100% oxygen which suppressed &gt;50% HITS in 10 (67%) patients. Conclusion: Patients supported by MCS devices produce unique and characteristic waveforms on TCD studies. Further studies will describe normative values in this special population. HITS were not universally present and intermittently suppressible by oxygen, suggesting some may be gaseous in nature. Risk of stroke in patients with MCS and HITS is under study.

Abstract 20670: Coronary Microembolization During Transfemoral Transcatheter Aortic Valve Implantation: An Intracoronary Doppler Study

Background: A postprocedural increase of the serum troponin I concentration (TnI) reflects myocardial injury and occurs frequently during transcatheter aortic valve implantation (TAVI). Periprocedural coronary microembolization is a potential cause of such injury. We therefore evaluated each step of the transfemoral TAVI procedure for coronary embolization using intracoronary Doppler (ICD) in the left anterior descending (LAD) artery. Methods: 15 high-risk patients with severe, symptomatic aortic valve stenosis (age 79 ± 45 yrs; EuroScore 17 ± 4%) who underwent transfemoral TAVI using the balloon-expandable Edwards bioprosthesis were included. ICD examinations were recorded and evaluated off-line for high-intensity transient signals (HITS). Perioperative concentrations of TnI were serially measured within the first 72 h after TAVI, and a cardiac MRI with late gadolinium-enhancement (LGE) was performed within 7 days. Results: HITS were detected in all patients (figure 1), mostly during the initial crossing of the native valve and positioning of the prosthesis with subsequent implantation. TnI peaked at 24 h after TAVI (3.17 ng/ml), and LGE was observed in only one single case. There was no correlation between amount of HITS and TnI area under the curve in the first 72 h after TAVI. Conclusions: Procedural HITS were detected by ICD in all patients undergoing transfemoral TAVI. The highest amount of HITS was observed during initial valve passage and positioning of the prosthesis with subsequent implantation. However, no association was found between the number of HITS and myocardial injury, as reflected by increased serum TnI concentrations or LGE on cardiac MRI.

Feasibility and exploratory efficacy evaluation of the Embrella Embolic Deflector system for the prevention of cerebral emboli in patients undergoing transcatheter aortic valve replacement: the PROTAVI-C pilot study.

This study sought to determine the feasibility, safety, and exploratory efficacy of the Embrella Embolic Deflector (EED) system (Edwards Lifesciences, Irvine, California) in patients undergoing transcatheter aortic valve replacement (TAVR). Few data exist on the value of using embolic protection devices during TAVR. This pilot study included 52 patients who underwent transfemoral TAVR. The EED system was used in 41patients, whereas 11 patients underwent TAVR without embolic protection (control group). Cerebral diffusion-weighted magnetic resonance imaging (DW-MRI) was performed at baseline and within 7 days and 30 days after TAVR. The EED system was successfully deployed at the level of the aortic arch in all patients with no complications. The deployment of the EED system was associated with high-intensity transient signals (HITS) as evaluated by transcranial Doppler (median: 48 [interquartile range: 17 to 198] HITS), and a higher total number of HITS was observed in the EED group (p< 0.001 vs. control group). DW-MRI performed within 7 days after TAVR showed the presence of new ischemic lesions in all patients in both groups, with a median number of 7 (interquartile range: 3 to 13) lesions per patient. The use of the EED system was associated with a lower lesion volume compared with the control group (p= 0.003). All new cerebral lesions had disappeared on the DW-MRI performed at 30 days after TAVR. Two strokes unrelated to the EED system occurred 2 and 29 days after TAVR. This study showed the feasibility and safety of using the EED system in TAVR procedures. The EED system did not prevent the occurrence of cerebral microemboli during TAVR or new transient ischemic lesions as evaluated by DW-MRI, but it was associated with a reduction in lesion volume. Further studies are warranted to determine the efficacy of using the EED system during TAVR procedures.

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Cerebral Embolization During Transcatheter Aortic Valve Implantation

Background— Transcatheter aortic valve implantation (TAVI) is associated with a higher risk of neurological events for both the transfemoral and transapical approach than surgical valve replacement. Cerebral magnetic resonance imaging has revealed more new, albeit clinically silent lesions from procedural embolization, yet the main source and predominant procedural step of emboli remain unclear. Methods and Results— Eighty-three patients underwent transfemoral (Medtronic CoreValve [MCV TF ], n=32; Edwards Sapien [ES TF ], n=26) and transapical (ES TA : n=25) TAVI. Serial transcranial Doppler examinations before, during, and 3 months after TAVI were used to identify high-intensity transient signals (HITS) as a surrogate for microembolization. Procedural HITS were detected in all patients, predominantly during manipulation of the calcified aortic valve while stent valves were being positioned and implanted. The balloon-expandable ES prosthesis caused significantly more HITS (mean [95% CI]) during positioning (ES TF , 259.9 [184.8–334.9]; ES TA , 206.1[162.5–249.7]; MCV TF , 78.5 [25.3–131.6]; P &lt;0.001) and the self-expandable MCV prosthesis during implantation (MCV TF , 397.1 [302.1–492.2]; ES TF , 88.2 [70.2–106.3]; ES TA , 110.7 [82.0–139.3]; P &lt;0.001). Overall, there were no significant differences between transfemoral and transapical TAVI or between the MCV and ES prostheses. No HITS were detected at baseline or 3-month follow-up. There was 1 major procedural stroke that resulted in death and 1 minor procedural stroke with full recovery at 3-month follow-up in the MCV group. Conclusions— Procedural HITS were detected by transcranial Doppler in all patients. Although no difference was observed between the transfemoral and the transapical approach with the balloon-expandable ES stent valve, transfemoral TAVI with the self-expandable MCV prosthesis resulted in the greatest number of HITS, predominantly during implantation.

Detection of coronary microembolization by Doppler ultrasound in patients with stable angina pectoris during percutaneous coronary interventions under an adjunctive antithrombotic therapy with abciximab: design and rationale of the High Intensity Transient Signals ReoPro (HITS-RP) study

BackgroundEmbolization of atherosclerotic debris from the rupture of a vulnerable atherosclerotic plaque occurs iatrogenically during percutaneous coronary interventions (PCI) and can induce myocardial necrosis. These microembolizations are detected as high intensity transient signals (HITS) using intracoronary Doppler technology.Presentation of the hypothesisIn the presented study we will test if abciximab (ReoPro®) infusion reduces high intensity transient signals in patients with stable angina pectoris undergoing PCI in comparison to standard therapy alone.Testing the hypothesisThe High Intensity Transient Signals ReoPro® (HITS-RP) study will enroll 60 patients. It is a prospective, single center, randomized, double-blinded, controlled trial. The study is designed to compare the efficacy of intravenous abciximab administration for reduction of microembolization during elective PCI. Patients will be randomized in a 1:1 fashion to abciximab or placebo infusion. The primary end point of the HITS-RP-Study is the number of HITS during PCI measured by intracoronary Doppler wire. Secondary endpoints are bleeding complications, elevation of cardiac biomarkers or ECG changes after percutaneous coronary interventions, changes in coronary flow velocity reserve, hs-CRP elevation, any major adverse cardio-vascular event during one month follow-up.Implications of the hypothesisThe HITS-RP-Study addresses important questions regarding the efficacy of intravenous abciximab administration in reducing microembolization and periprocedural complications in stable angina pectoris patients undergoing PCI.Trial registrationThe trial is registered under http://www.drks-neu.uniklinik-freiburg.de/drks_web/:DRKS00000603.

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.

Predictability of Cerebral Embolization from Aortic Arch Manipulations During Thoracic Endovascular Repair

There is no sensitive tool to monitor embolic events and predict patients at a risk for strokes during thoracic endovascular aortic repair. We examined the relationship between the number of high intensity transient signals (HITS) by transcranial doppler ultrasound and the extent of atherosclerotic plaques in aortic arch. Thirteen patients were treated as a part of a single center United States Food and Drug Administration-approved investigational device exemption for various thoracic aortic pathologies. Bilateral transcranial doppler ultrasound transducers recorded the number of HITS. CT angiography and intravascular ultrasound were used to measure the thickness of mural thrombi and determine their arch location. All 13 patients had detectable HITS, and one patient sustained a stroke. Eleven patients had quantifiable mural thrombi. The highest HITS were observed in patients with thrombi in zones 2 to 3. All three patients with bovine arch had more HITS in the right middle cerebral artery whereas the patients with normal arch anatomy had more HITS in the left middle cerebral artery. The presence of mural thrombi in zones 2 and 3, irrespective of their thickness, was associated with increased HITS during thoracic endovascular aortic repair. This is the first study to characterize the significance of mural thrombi in aortic arch and their relationship to embolic events during aortic arch manipulations.

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.