Cerebral Embolic Protection during Transcatheter Aortic-Valve Replacement.

BACKGROUND: Transcatheter aortic-valve replacement (TAVR) for the treatment of aortic stenosis can lead to embolization of debris. Capture of debris by devices that provide cerebral embolic protection (CEP) may reduce the risk of stroke. METHODS: We randomly assigned patients with aortic stenosis in a 1:1 ratio to undergo transfemoral TAVR with CEP (CEP group) or without CEP (control group). The primary end point was stroke within 72 hours after TAVR or before discharge (whichever came first) in the intention-to-treat population. Disabling stroke, death, transient ischemic attack, delirium, major or minor vascular complications at the CEP access site, and acute kidney injury were also assessed. A neurology professional examined all the patients at baseline and after TAVR. RESULTS: A total of 3000 patients across North America, Europe, and Australia underwent randomization; 1501 were assigned to the CEP group and 1499 to the control group. A CEP device was successfully deployed in 1406 of the 1489 patients (94.4%) in whom an attempt was made. The incidence of stroke within 72 hours after TAVR or before discharge did not differ significantly between the CEP group and the control group (2.3% vs. 2.9%; difference, -0.6 percentage points; 95% confidence interval, -1.7 to 0.5; P = 0.30). Disabling stroke occurred in 0.5% of the patients in the CEP group and in 1.3% of those in the control group. There were no substantial differences between the CEP group and the control group in the percentage of patients who died (0.5% vs. 0.3%); had a stroke, a transient ischemic attack, or delirium (3.1% vs. 3.7%); or had acute kidney injury (0.5% vs. 0.5%). One patient (0.1%) had a vascular complication at the CEP access site. CONCLUSIONS: Among patients with aortic stenosis undergoing transfemoral TAVR, the use of CEP did not have a significant effect on the incidence of periprocedural stroke, but on the basis of the 95% confidence interval around this outcome, the results may not rule out a benefit of CEP during TAVR. (Funded by Boston Scientific; PROTECTED TAVR ClinicalTrials.gov number, NCT04149535.).

Leaflet modification before transcatheter aortic valve implantation in patients at risk for coronary obstruction: the ShortCut study.

BACKGROUND AND AIMS: This trial sought to assess the safety and efficacy of ShortCut, the first dedicated leaflet modification device, prior to transcatheter aortic valve implantation (TAVI) in patients at risk for coronary artery obstruction. METHODS: This pivotal prospective study enrolled patients with failed bioprosthetic aortic valves scheduled to undergo TAVI and were at risk for coronary artery obstruction. The primary safety endpoint was procedure-related mortality or stroke at discharge or 7 days, and the primary efficacy endpoint was per-patient leaflet splitting success. Independent angiographic, echocardiographic, and computed tomography core laboratories assessed all images. Safety events were adjudicated by a clinical events committee and data safety monitoring board. RESULTS: Sixty eligible patients were treated (77.0 ± 9.6 years, 70% female, 96.7% failed surgical bioprosthetic valves, 63.3% single splitting and 36.7% dual splitting) at 22 clinical sites. Successful leaflet splitting was achieved in all [100%; 95% confidence interval (CI) 94%-100.0%, P < .001] patients. Procedure time, including imaging confirmation of leaflet splitting, was 30.6 ± 17.9 min. Freedom from the primary safety endpoint was achieved in 59 [98.3%; 95% CI (91.1%-100%)] patients, with no mortality and one (1.7%) disabling stroke. At 30 days, freedom from coronary obstruction was 95% (95% CI 86.1%-99.0%). Within 90 days, freedom from mortality was 95% [95% CI (86.1%-99.0%)], without any cardiovascular deaths. CONCLUSIONS: Modification of failed bioprosthetic aortic valve leaflets using ShortCut was safe, achieved successful leaflet splitting in all patients, and was associated with favourable clinical outcomes in patients at risk for coronary obstruction undergoing TAVI.

Echocardiographic Versus Invasive Aortic Valve Gradients in Different Clinical Scenarios.

BACKGROUND: The role of echocardiography in deriving transvalvular mean gradients from transaortic velocities in aortic stenosis (AS) and in structural valve degeneration (SVD) is well established. However, reports following surgical aortic valve replacement, post-transcatheter aortic valve replacement (TAVR), and valve-in-valve-TAVR (ViV-TAVR) have cautioned against the use of echocardiography-derived mean gradients to assess normal functioning bioprosthesis due to discrepancy compared with invasive measures in a phenomenon called discordance. METHODS: In a multicenter study, intraprocedural echocardiographic and invasive mean gradients in AS, SVD, post-native TAVR, and post-ViV-TAVR were compared, when obtained concomitantly, and discharge echocardiographic gradients were recorded. Absolute discordance (intraprocedural echocardiographic - invasive mean gradient) and percent discordance (intraprocedural echocardiographic - invasive mean gradient/echocardiographic mean gradient) were calculated. Multivariable regression analysis was performed to determine variables independently associated with elevated postprocedure invasive gradients ≥20 mm Hg, absolute discordance >10 mm Hg, and discharge echocardiographic mean gradient ≥20 mm Hg. RESULTS: A total of 5,027 patients were included in the registry: 4,725 native TAVR and 302 ViV-TAVR. Intraprocedural concomitant echocardiographic and invasive mean gradients were obtained pre-TAVR in AS (n = 2,418), pre-ViV-TAVR in SVD (n = 101), in post-ViV-TAVR (n = 77), and in post-TAVR (n = 823). Echocardiographic and invasive mean gradients demonstrated strong correlation (r = 0.69) and agreement (bias, 0.11; 95% CI, -0.4-0.62) in AS, moderate correlation (r = 0.56) and agreement (bias, 1.08; 95% CI, -2.53 to 4.59) in SVD, moderate correlation (r = 0.61) and weak agreement (bias, 6.47; 95% CI, 5.08-7.85) post-ViV-TAVR, and weak correlation (r = 0.18) and agreement (bias, 3.41; 95% CI, 3.16-3.65) post-TAVR. Absolute discordance occurs primarily in ViV-TVR and is not explained by sinotubular junction size and increases with increasing echocardiographic mean gradient. Percent discordance in AS and SVD (1.3% and 4%, respectively) was lower compared with post-TAVR/ViV-TAVR (66.7% and 100%, respectively). Compared with self-expanding valves, balloon expanding valves were independently associated with elevated discharge echocardiographic but lower invasive mean gradient (odds ratio = 3.411, 95% CI, 1.482-7.852, P = .004; vs odds ratio = 0.308, 95% CI, 0.130-0.731, P = .008, respectively). CONCLUSIONS: Post-TAVR/ViV-TAVR, echocardiography is discordant from invasive mean gradients, and absolute discordance increases with increasing echocardiographic mean gradient and is not explained by sinotubular junction size. Percent discordance is significantly higher post-TAVR/ViV-TAVR than in AS and SVD. Post-TAVR/ViV-TAVR, poor correlation and wide limits of agreement suggest echocardiographic and invasive mean gradients may not be used interchangeably and a high residual echocardiographic mean gradient should be confirmed invasively before considering any additional procedure to "correct" the gradient. Transcatheter aortic valve replacement valve types have variable impact on echocardiographic and invasive mean gradients.

Design and Rationale of the Safe Surveillance of PCI Under Mechanical Circulatory Support With the Saranas Early Bird Bleed Monitoring System (SAFE-MCS) Study.

Background: High-risk percutaneous coronary intervention (PCI) with mechanical circulatory support (MCS) has been associated with varying rates of bleeding due to variable bleeding definitions, incomplete data relative to site-specific bleeding, and inclusion of variable patient populations. Study Design and Objectives: SAFE-MCS (NCT05077657) is a multicenter, single-arm, open-label study designed to evaluate the safety of complex high-risk PCI using Impella and surveillance with the Saranas Early Bird Bleed Monitoring System (EBBMS). The study aims to enroll 184 evaluable subjects at up to 15 US centers. The primary clinical end point is the incidence of access-site related BARC type III or V bleeding. Secondary clinical end points include the incidence of each of the Saranas EBBMS level 1, 2, and 3 indicators and the incidence of all BARC type III or V bleeding. Enrollment is anticipated to complete in September 2023 with no longitudinal follow-up. Conclusions: SAFE-MCS is the first study to exclusively assess bleeding complications in patients undergoing PCI with Impella with independent adjudication via a clinical end point committee and will gather meaningful real-world data using contemporary practice.

Transvalvular Pressure Gradients and All-Cause Mortality Following TAVR: A Multicenter Echocardiographic and Invasive Registry.

BACKGROUND: Low ejection fraction (EF) and low flow as determined by an echocardiographic stroke volume index (SVi) <35 mL/m2 are associated with low transvalvular gradients and increased mortality in both severe aortic stenosis (AS) and post-transcatheter aortic valve replacement (TAVR). Absence of an elevated echocardiographic transaortic gradient post-TAVR is considered a marker of procedural success despite the absence of data on its impact on mortality. OBJECTIVES: The authors sought to examine the association of invasive and echocardiographic gradients post-TAVR with all-cause mortality in relation to flow and EF. METHODS: In a multicenter retrospective registry of patients undergoing TAVR, Cox models with regression splines explored the relationship between invasive and echocardiographic gradients post-TAVR with 2-year mortality. An invasive gradient <5 mm Hg was considered low, between ≥5 and <10 mm Hg was considered intermediate, and ≥10 mm Hg was considered high. An echocardiographic gradient <10 mm Hg was considered low, ≥10 and <20 mm Hg was considered intermediate, and ≥20 mm Hg was considered high. RESULTS: Higher mortality occurred in low echocardiographic gradients at discharge relative to intermediate gradients (P < 0.001), and low gradient was associated with lower EF and echocardiographic SVi (P < 0.001 and P < 0.008, respectively). Lower mortality occurred in low invasive gradients relative to intermediate gradients (P = 0.012) with no difference in EF and echocardiographic SVi between groups (P = 0.089 and P = 0.947, respectively). There were insufficient observations to determine the impact of high echocardiographic and invasive gradients on mortality. CONCLUSIONS: In this large retrospective analysis, the impact of transaortic gradients on mortality after TAVR was not linear and complex, showing opposite results among echocardiographic and invasive measurements in low-gradient patients.

Ejection Fraction Improvement Following Contemporary High-Risk Percutaneous Coronary Intervention: RESTORE EF Study Results.

Background: Despite many reports of clinical outcomes in patients undergoing high-risk percutaneous coronary intervention (HRPCI) with hemodynamic support, little is known about whether this approach improves left ventricular ejection fraction (LVEF). The purpose of the present observational study was to examine, in an ideal patient population with Impella-supported HRPCI, whether there is an impact on left ventricular function at midterm follow-up. Methods: RESTORE EF is a multicenter, retrospective analysis of a prospectively collected observational data set that aimed to assess 90-day LVEF in patients undergoing Impella-supported nonemergent HRPCI (NCT04648306), who survived with no intervening cardiac procedures prior to the primary endpoint follow-up window (90-day LVEF assessment). Secondary endpoints included change in New York Heart Association Functional Classification and Canadian Cardiovascular Society Angina Grade at the last follow-up. Results: From August 2019 to May 2021, 406 patients were enrolled at 22 US sites. Age was 70.2 â€‹â€‹± â€‹â€‹11.4 â€‹â€‹years; 26% were female. In paired assessment at 90-day follow-up, baseline LVEF improved from 35 â€‹â€‹± â€‹â€‹15% to 45 â€‹â€‹± â€‹â€‹14% (N = 251, P < .0001), with significantly greater improvement in patients with residual SYNTAX score I of 0. Percentage classified as New York Heart Association class III/IV decreased from 62% at baseline to 15% at last follow-up (P < .001), and percentage with Canadian Cardiovascular Society grade III/IV symptoms decreased from 72% to 2% (P < .0001). Conclusions: In an ideal cohort of HRPCI patients, there is a signal that hemodynamically supported HRPCI affords significant improvement in 90-day LVEF, with complete revascularization associated with greater LVEF improvement. These hypothesis-generating findings merit further assessment in large, all-comer studies and randomized trials.

Comparison of Transvalvular Aortic Mean Gradients Obtained by Intraprocedural Echocardiography and Invasive Measurement in Balloon and Self-Expanding Transcatheter Valves.

Background Concerns about discordance between echocardiographic and invasive mean gradients after transcatheter aortic valve replacement (TAVR) with balloon-expandable valves (BEVs) versus self-expanding valves (SEVs) exist. Methods and Results In a multicenter study, direct-invasive and echocardiography-derived transvalvular mean gradients obtained before and after TAVR were compared as well as post-TAVR and discharge echocardiographic mean gradients in BEVs versus SEVs in 808 patients. Pre-TAVR, there was good correlation (R=0.614; P<0.0001) between direct-invasive and echocardiography-derived mean gradients and weak correlation (R=0.138; P<0.0001) post-TAVR. Compared with post-TAVR echocardiographic mean gradients, both valves exhibit lower invasive and higher discharge echocardiographic mean gradients. Despite similar invasive mean gradients, a small BEV exhibits higher post-TAVR and discharge echocardiographic mean gradients than a large BEV, whereas small and large SEVs exhibit similar post-TAVR and discharge mean gradients. An ejection fraction <50% (P=0.028) and higher Society of Thoracic Surgeons predicted risk of mortality score (P=0.007), but not invasive or echocardiographic mean gradient ≥10 mm Hg (P=0.378 and P=0.341, respectively), nor discharge echocardiographic mean gradient ≥20 mm Hg (P=0.393), were associated with increased 2-year mortality. Conclusions Invasively measured and echocardiography-derived transvalvular mean gradients correlate well in aortic stenosis but weakly post-TAVR. Post-TAVR, echocardiography overestimates transvalvular mean gradients compared with invasive measurements, and poor correlation suggests these modalities cannot be used interchangeably. Moreover, echocardiographic mean gradients are higher on discharge than post-TAVR in all valves. Despite similar invasive mean gradients, a small BEV exhibits higher post-TAVR and discharge echocardiographic mean gradients than a large BEV, whereas small and large SEVs exhibit similar post-TAVR and discharge mean gradients. Immediately post-TAVR, elevated echocardiographic-derived mean gradients should be assessed with caution and compared with direct-invasive mean gradients. A low ejection fraction and higher Society of Thoracic Surgeons score, but not elevated mean gradients, are associated with increased 2-year mortality.

The effect of venous thrombus location and extent on the development of post-thrombotic signs and symptoms.

OBJECTIVE: This prospective study determined the incidence of signs and symptoms of chronic venous disease and recurrent venous thrombotic events (VTE) in relation to the location and extent of the initial venous thrombus. METHODS: A first episode of acute deep vein thrombosis (DVT) occurred in 120 lower extremities of 105 patients (59 men; mean age, 54 years [range, 23-82 years]). Patients who presented with pain, swelling, or signs and symptoms of pulmonary embolism of <10 days were included. The DVT was diagnosed with duplex ultrasound (DUS) imaging. Patients were grouped by those having thrombosis in one venous segment (group A) or multiple levels (group B). Patients were treated with heparin and warfarin. Patients with at least 1-year of follow-up with clinical and DUS were included. RESULTS: No difference was found in the duration of signs and symptoms at presentation. The median follow-up was 3.4 years (range, 1.2-7 years). More symptomatic limbs were seen in group B (71 of 79) compared with group A (21 of 41; P < .001). Post-thrombotic syndrome (PTS) was more advanced in group B vs group A, including the prevalence of skin damage and ulceration (61 of 79 vs 26 of 41, P < .001; 29 of 79 vs 6 of 41, P = .019, respectively). Limbs with calf DVT that had focal thrombosis were most often asymptomatic. Calf thrombosis in patients with proximal DVT produced the highest prevalence of PTS. Venous claudication was exclusively found in group B and was present only when iliac veins were involved. Recurrent thrombosis had a trend for a higher prevalence in group B (5 of 41 vs 16 of 79, P = .39). Reflux, obstruction, or a combination of the two were more common in group B (61 of 79) vs group A (15 of 41; P < .0001). Limbs with both reflux and obstruction were more likely to develop skin damage (group A, 5 of 6 vs 1 of 35, P < .0001; group B, 24 of 29 vs 5 of 50, P < .0001). CONCLUSIONS: Recurrent thrombosis and skin damage is more likely to develop in patients with multiple sites of thrombosis than in those with thrombosis in a single vein segment. Patients with reflux and obstruction presented more skin damage than those with reflux or obstruction alone. Involvement of the calf veins in the presence of proximal vein thrombosis increased the likelihood for PTS.

Engineering of a miniaturized, robotic clinical laboratory.

The ability to perform laboratory testing near the patient and with smaller blood volumes would benefit patients and physicians alike. We describe our design of a miniaturized clinical laboratory system with three components: a hardware platform (ie, the miniLab) that performs preanalytical and analytical processing steps using miniaturized sample manipulation and detection modules, an assay-configurable cartridge that provides consumable materials and assay reagents, and a server that communicates bidirectionally with the miniLab to manage assay-specific protocols and analyze, store, and report results (i.e., the virtual analyzer). The miniLab can detect analytes in blood using multiple methods, including molecular diagnostics, immunoassays, clinical chemistry, and hematology. Analytical performance results show that our qualitative Zika virus assay has a limit of detection of 55 genomic copies/ml. For our anti-herpes simplex virus type 2 immunoglobulin G, lipid panel, and lymphocyte subset panel assays, the miniLab has low imprecision, and method comparison results agree well with those from the United States Food and Drug Administration-cleared devices. With its small footprint and versatility, the miniLab has the potential to provide testing of a range of analytes in decentralized locations.

A unique complication of the GuideZilla guide extension support catheter and the risk of stent stripping in interventional & endovascular interventions.

Supporting catheters in percutaneous stenting of anatomically difficult coronary lesions are utilized by interventional cardiologists. The GuideZilla guide extension catheter is designed for deep seating in coronary arteries to provide extra guidance support for equipment delivery during difficult coronary interventions or for coaxial alignment in tortuous vessels. There are limited GuideZilla-related complications reported in the literature. We present a challenging case of a left main and left anterior descending artery dissection, complicated with stent stripping off the delivery balloon by the GuideZilla support catheter.