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Severe pure aortic regurgitation (AR) carries a high mortality and morbidity risk, and it is often undertreated because of the inherent surgical risk. Transcatheter heart valves (THVs) have been used off-label in this setting with overall suboptimal results. The dedicated "purpose-built" Jena Valve Trilogy (JVT, JenaValve Technology) showed an encouraging performance, although it has never been compared to other THVs. The aim of our study was to assess the performance of the latest iteration of THVs used off-label in comparison to the purpose-built JVT in inoperable patients with severe AR. We performed a multicenter, retrospective registry with 18 participating centers worldwide collecting data on inoperable patients with severe AR of the native valve. A bicuspid aortic valve was the main exclusion criterion. The primary endpoints were technical and device success, 1-year all-cause mortality, and the composite of 1-year mortality and the heart failure rehospitalization rate. Overall, 256 patients were enrolled. THVs used off-label were used in 168 cases (66%), whereas JVT was used in 88 (34%). JVT had higher technical (81% vs 98%; P < 0.001) and device success rates (73% vs 95%; P < 0.001), primarily driven by significantly lower incidences of THV embolization (15% vs 1.1%; P < 0.001), the need for a second valve (11% vs 1.1%; P = 0.004), and moderate residual AR (10% vs 1.1%; P = 0.007). The permanent pacemaker implantation rate was comparable and elevated for both groups (22% vs 24%; P = 0.70). Finally, no significant difference was observed at the 1-year follow-up in terms of mortality (HR: 0.99; P = 0.980) and the composite endpoint (HR: 1.5; P = 0.355). The JVT platform has a better acute performance than other THVs when used off-label for inoperable patients with severe AR. A longer follow-up is conceivably needed to detect a possible impact on prognosis. [Display omitted] [ABSTRACT FROM AUTHOR]

Symptomatic patients with severe aortic stenosis (AS) at high risk for surgical aortic valve replacement (SAVR) sustain comparable improvements in health status over 5 years after transcatheter aortic valve replacement (TAVR) or SAVR. Whether a similar long-term benefit is observed among intermediate-risk AS patients is unknown. The purpose of this study was to assess health status outcomes through 5 years in intermediate risk patients treated with a self-expanding TAVR prosthesis or SAVR using data from the SURTAVI (Surgical Replacement and Transcatheter Aortic Valve Implantation) trial. Intermediate-risk patients randomized to transfemoral TAVR or SAVR in the SURTAVI trial had disease-specific health status assessed at baseline, 30 days, and annually to 5 years using the Kansas City Cardiomyopathy Questionnaire (KCCQ). Health status was compared between groups using fixed effects repeated measures modelling. Of the 1,584 patients (TAVR, n = 805; SAVR, n = 779) included in the analysis, health status improved more rapidly after TAVR compared with SAVR. However, by 1 year, both groups experienced large health status benefits (mean change in KCCQ-Overall Summary Score (KCCQ-OS) from baseline: TAVR: 20.5 ± 22.4; SAVR: 20.5 ± 22.2). This benefit was sustained, albeit modestly attenuated, at 5 years (mean change in KCCQ-OS from baseline: TAVR: 15.4 ± 25.1; SAVR: 14.3 ± 24.2). There were no significant differences in health status between the cohorts at 1 year or beyond. Similar findings were observed in the KCCQ subscales, although a substantial attenuation of benefit was noted in the physical limitation subscale over time in both groups. In intermediate-risk AS patients, both transfemoral TAVR and SAVR resulted in comparable and durable health status benefits to 5 years. Further research is necessary to elucidate the mechanisms for the small decline in health status noted at 5 years compared with 1 year in both groups. (Safety and Efficacy Study of the Medtronic CoreValve® System in the Treatment of Severe, Symptomatic Aortic Stenosis in Intermediate Risk Subjects Who Need Aortic Valve Replacement [SURTAVI]; NCT01586910) [Display omitted] [ABSTRACT FROM AUTHOR]

Data on valve reintervention after transcatheter aortic valve replacement (TAVR) or surgical aortic valve replacement (SAVR) are limited. The authors compared the 5-year incidence of valve reintervention after self-expanding CoreValve/Evolut TAVR vs SAVR. Pooled data from CoreValve and Evolut R/PRO (Medtronic) randomized trials and single-arm studies encompassed 5,925 TAVR (4,478 CoreValve and 1,447 Evolut R/PRO) and 1,832 SAVR patients. Reinterventions were categorized by indication, timing, and treatment. The cumulative incidence of reintervention was compared between TAVR vs SAVR, Evolut vs CoreValve, and Evolut vs SAVR. There were 99 reinterventions (80 TAVR and 19 SAVR). The cumulative incidence of reintervention through 5 years was higher with TAVR vs SAVR (2.2% vs 1.5%; P = 0.017), with differences observed early (≤1 year; adjusted subdistribution HR: 3.50; 95% CI: 1.53-8.02) but not from >1 to 5 years (adjusted subdistribution HR: 1.05; 95% CI: 0.48-2.28). The most common reason for reintervention was paravalvular regurgitation after TAVR and endocarditis after SAVR. Evolut had a significantly lower incidence of reintervention than CoreValve (0.9% vs 1.6%; P = 0.006) at 5 years with differences observed early (adjusted subdistribution HR: 0.30; 95% CI: 0.12-0.73) but not from >1 to 5 years (adjusted subdistribution HR: 0.61; 95% CI: 0.21-1.74). The 5-year incidence of reintervention was similar for Evolut vs SAVR (0.9% vs 1.5%; P = 0.41). A low incidence of reintervention was observed for CoreValve/Evolut R/PRO and SAVR through 5 years. Reintervention occurred most often at ≤1 year for TAVR and >1 year for SAVR. Most early reinterventions were with the first-generation CoreValve and managed percutaneously. Reinterventions were more common following CoreValve TAVR compared with Evolut TAVR or SAVR. [Display omitted] [ABSTRACT FROM AUTHOR]

Coronary obstruction (CO) is a potentially life-threatening complication of transcatheter aortic valve replacement (TAVR). Chimney stenting or leaflet laceration with transcatheter electrosurgery (Bioprosthetic or Native Aortic Scallop Intentional Laceration to Prevent Iatrogenic Coronary Artery Obstruction [BASILICA]) are 2 techniques developed to prevent CO. The aim of the present study was to compare periprocedural and 1-year outcomes of chimney and BASILICA in TAVR patients at high risk of CO. This multicenter observational registry enrolled consecutive TAVR patients at high risk of CO, undergoing either preventive chimney stenting or BASILICA. Clinical success was defined as successful performance of the chimney or BASILICA technique without clinically relevant ostial CO. The primary endpoint was major adverse cardiovascular events, a composite of death, myocardial infarction, stroke, or unplanned target lesion coronary revascularization at 1 year. A total of 168 patients were included: 71 (42.3%) received chimney stenting, and 97 (57.7%) underwent BASILICA. Patients undergoing BASILICA had higher preprocedural risk of CO, as indicated by lower sinotubular junction height (18.2 ± 4.8 mm vs 14.8 ± 3.4 mm; P < 0.001) and diameter (28.2 ± 4.5 vs 26.8 ± 3.4; P = 0.029). Rates of periprocedural complications were similar between the 2 groups. Clinical success was 97.2% and 96.9% in chimney and BASILICA, respectively (P = 0.92). At 1-year follow-up, the cumulative incidence of major adverse cardiovascular events was 18.7% (95% CI: 11%-30.6%) in the chimney group and 19.9% (95% CI: 12.1%-31.5%) in the BASILICA group (log-rank P = 0.848), whereas chimney was associated with a numerically higher cardiovascular mortality than BASILICA (6.7% vs 1.3%; log-rank P = 0.168). Chimney stenting and BASILICA effectively prevent TAVR-induced acute CO. Both techniques seem to have comparable acceptable periprocedural and 1-year outcomes. [Display omitted] [ABSTRACT FROM AUTHOR]

Acute ischemic stroke remains a serious complication of transcatheter aortic valve replacement (TAVR). Cerebral embolic protection devices (CEPD) were developed to mitigate the risk of acute ischemic stroke complicating TAVR (AISCT). However, the existing body of evidence does not clearly support CEPD efficacy in AISCT prevention. In a cohort of patients with AISCT, we aimed to compare the characteristics and outcomes of patients who have had unprotected TAVR (CEPD−) vs CEPD-protected TAVR (CEPD+). Data were derived from an international multicenter registry focusing on AISCT. We included all patients who experienced ischemic stroke within 72 hours of TAVR. Stroke severity was assessed using the National Institutes of Health Stroke Scale (NIHSS). Primary outcomes were neurologic disability status according to the modified Rankin Score at 30 days, and 6-month all-cause death. Propensity score matched analysis was used to control for differences between groups. In 18,725 TAVR procedures, 416 AISCT (2.2%) within 72 hours were documented, of which 376 were in the CEPD− TAVR group and 40 in the CEPD+ TAVR group. Although the middle cerebral artery stroke rate was similar in both groups (29.7% CEPD− vs 33.3% CEPD+; P = 0.71), AISCT in the CEPD+ group was characterized by a lower rate of internal carotid artery occlusion (0% vs 4.7%) and higher rate of vertebrobasilar system strokes (15.4% vs 5.7%; P = 0.04). AISCT was severe (NIHSS ≥15) in 21.6% CEPD− and 23.3% CEPD+ AISCT (P = 0.20). Disabling stroke rates (modified Rankin Score >1 at 30 days) were 47.3% vs 42.5% (P = 0.62), and 6-month mortality was 31.3% vs 23.3% (P = 0.61), in the CEPD− and CEPD+ groups, respectively. In the propensity score matched cohort, disabling stroke rates were 56.5% vs 41.6% (P = 0.16), and 6-month mortality was 33% vs 19.5% (P = 0.35), in the CEPD− and CEPD+ groups, respectively. In a large cohort of patients with AISCT, the use of CEPD had little effect on stroke distribution, severity, and outcomes. [Display omitted] [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic adversely affected health care systems. Patients in need of transcatheter aortic valve replacement (TAVR) are especially susceptible to treatment delays. This study sought to evaluate the impact of the COVID-19 pandemic on global TAVR activity. This international registry reported monthly TAVR case volume in participating institutions prior to and during the COVID-19 pandemic (January 2018 to December 2021). Hospital-level information on public vs private, urban vs rural, and TAVR volume was collected, as was country-level information on socioeconomic status, COVID-19 incidence, and governmental public health responses. We included 130 centers from 61 countries, including 65,980 TAVR procedures. The first and second pandemic waves were associated with a significant reduction of 15% (P < 0.001) and 7% (P < 0.001) in monthly TAVR case volume, respectively, compared with the prepandemic period. The third pandemic wave was not associated with reduced TAVR activity. A greater reduction in TAVR activity was observed in Africa (−52%; P = 0.001), Central-South America (−33%; P < 0.001), and Asia (−29%; P < 0.001). Private hospitals (P = 0.005), urban areas (P = 0.011), low-volume centers (P = 0.002), countries with lower development (P < 0.001) and economic status (P < 0.001), higher COVID-19 incidence (P < 0.001), and more stringent public health restrictions (P < 0.001) experienced a greater reduction in TAVR activity. TAVR procedural volume declined substantially during the first and second waves of the COVID-19 pandemic, especially in Africa, Central-South America, and Asia. National socioeconomic status, COVID-19 incidence, and public health responses were associated with treatment delays. This information should inform public health policy in case of future global health crises. [Display omitted] [ABSTRACT FROM AUTHOR]

Segmental postpercutaneous coronary intervention (PCI) pressure gradients may detect residual disease and potential targets for optimization. However, universal definitions of relevant segmental gradients are lacking. This study sought to evaluate the diagnostic performance of post-PCI fractional flow reserve (FFR), distal coronary pressure-to-aortic pressure ratio (Pd/Pa), and diastolic pressure ratio (dPR) gradients to detect residual focal lesions and stent underexpansion as observed by intravascular ultrasound (IVUS). Patients from the IVUS-guided optimization arm of the FFR REACT (FFR-guided PCI Optimization Directed by High-Definition IVUS Versus Standard of Care) trial with complete IVUS and FFR pullback data were included. Patients with angiographically successful PCI and post-PCI FFR <0.90 underwent FFR, Pd/Pa, and IVUS pullbacks. dPR was calculated offline using dedicated software. Segmental pressure gradients (distal, in stent, and proximal) in segments ≥5 mm were evaluated against IVUS-detected residual disease (distal or proximal focal lesions and stent underexpansion). A total of 139 vessels were included (mean post-PCI FFR: 0.83 ± 0.05, range 0.56-0.89). Focal distal and proximal lesions were detected by IVUS in 23 (17.4%) of 132 and 14 (12.6%) of 111 vessels, respectively, whereas stent underexpansion was present in 86 (61.9%) vessels. Diagnostic ability of segmental FFR gradients to predict IVUS-detected distal and proximal lesions was moderate-to-good (area under the curve [AUC]: 0.69 and 0.84, respectively) and poor to moderate for segmental Pd/Pa and dPR gradients (AUC ranging from 0.58 to 0.69). In-stent gradients had no discriminative ability to detect stent underexpansion (FFR AUC: 0.52; Pd/Pa AUC: 0.54; dPR AUC: 0.55). In patients with post-PCI FFR <0.90, segmental post-PCI pressure gradients have moderate discriminative ability to identify IVUS-detected focal lesions but no discriminative ability to identify IVUS-detected stent underexpansion. [Display omitted] [ABSTRACT FROM AUTHOR]

Current guidelines recommend that clinical surveillance for patients with moderate aortic stenosis (AS) and aortic valve replacement (AVR) may be considered if there is an indication for coronary revascularization. Recent observational studies, however, have shown that moderate AS is associated with an increased risk of cardiovascular events and mortality. Whether the increased risk of adverse events is caused by associated comorbidities, or to the underlying moderate AS itself, is incompletely understood. Similarly, which patients with moderate AS need close follow-up or could potentially benefit from early AVR is also unknown. In this review, the authors provide a comprehensive overview of the current published reports on moderate AS. They first provide an algorithm that helps to diagnose moderate AS correctly, especially when discordant grading is observed. Although the traditional focus of AS assessment has been on the valve, it is increasingly acknowledged that AS is not only a disease of the aortic valve but also of the ventricle. The authors therefore discuss how multimodality imaging can help to evaluate the left ventricular remodeling response and improve risk stratification in patients with moderate AS. Finally, they summarize current evidence on the management of moderate AS and highlight ongoing trials on AVR in moderate AS. [Display omitted] • Moderate AS is associated with a high risk of adverse cardiovascular events, including death. • DSE and cardiac CT can help to improve an accurate diagnosis of moderate AS. • Multimodality imaging can help to evaluate the left ventricular remodeling response caused by the underlying moderate AS. • Randomized controlled trials are ongoing to evaluate whether AVR can improve outcomes in patients with moderate AS. [ABSTRACT FROM AUTHOR]

Left main coronary artery (LMA) disease jeopardizes a large area of myocardium and increases the risk of major adverse cardiovascular events. LMCA disease is found in 5% to 7% of all diagnostic coronary angiographies, and more than 80% of the patients enrolled in recent large randomized controlled left main trials had distal left main bifurcation or trifurcation disease. Emerging clinical evidence from prospective all-comer registries and randomized trials has provided a solid basis for percutaneous coronary intervention as a treatment option in selected patients with unprotected LMCA disease; however, to date, no uniform recommendations as to optimal stenting strategy for LMCA bifurcation lesions exist. This review provides an overview of provisional stenting technique and escalation to 2-stent strategies in LMCA bifurcation lesions. Data from randomized controlled trials and registries are reviewed. Technical characteristics of optimal provisional LMCA stenting technique and angiographic and intravascular determinants of escalation are also summarized. [Display omitted] • PCI with DES is currently an evidence-based treatment strategy for left main bifurcation disease. • Intravascular imaging should be considered to complement conventional angiography in the evaluation of left main stem disease and technique for PCI using a provisional stent strategy. • Further research should focus on a tailored approach to optimize treatment strategies based on distal left main phenotypes. [ABSTRACT FROM AUTHOR]

The mechanisms underlying the increased risk of bleeding that female patients with ST-segment Elevation Myocardial Infarction (STEMI) exhibit, remains unclear. The present report assessed sex-related differences in response to pre-hospital dual antiplatelet therapy (DAPT) initiation in patients with STEMI. The COMPARE CRUSH trial randomized patients presenting with STEMI to receive a pre-hospital loading dose of crushed or integral prasugrel tablets in the ambulance. In this substudy, we compared platelet reactivity levels and the occurrence of high platelet reactivity (HPR; defined as platelet reactivity ≥208) between sexes at 4 prespecified time points after DAPT initiation, and evaluated post-PCI bleeding between groups. Out of 633 STEMI patients, 147 (23%) were female. Females compared with males presented with significantly higher levels of platelet reactivity and higher HPR rates at baseline (232 [IQR, 209-256] vs 195 [IQR, 171-220], P <.01, and 76% vs 41%, OR 4.58 [95%CI, 2.52-8.32], P <.01, respectively). Moreover, female sex was identified as the sole independent predictor of HPR at baseline (OR 5.67 [95%CI, 2.56-12.53], P <.01). Following DAPT initiation, levels of platelet reactivity and the incidence of HPR were similar between sexes. Post-PCI bleeding occurred more frequently in females compared with males (10% vs 2%, OR 6.02 [95%CI, 2.61-11.87], P <.01). Female sex was an independent predictor of post-PCI bleeding (OR 3.25 [95%CI, 1.09-9.72], P =.04). In this contemporary STEMI cohort, female STEMI patients remain at risk of bleeding complications after primary PCI. However, this is not explained by sex-specific differences in the pharmacodynamic response to pre-hospital DAPT initiation. [ABSTRACT FROM AUTHOR]

The optimal access route in patients with severe peripheral artery disease (PAD) undergoing transcatheter aortic valve replacement (TAVR) remains undetermined. This study sought to compare clinical outcomes with transfemoral access (TFA), transthoracic access (TTA), and nonthoracic transalternative access (TAA) in TAVR patients with severe PAD. Patients with PAD and hostile femoral access (TFA impossible, or possible only after percutaneous treatment) undergoing TAVR at 28 international centers were included in this registry. The primary endpoint was the propensity-adjusted risk of 30-day major adverse events (MAE) defined as the composite of all-cause mortality, stroke/transient ischemic attack (TIA), or main access site–related Valve Academic Research Consortium 3 major vascular complications. Outcomes were also stratified according to the severity of PAD using a novel risk score (Hostile score). Among the 1,707 patients included in the registry, 518 (30.3%) underwent TAVR with TFA after percutaneous treatment, 642 (37.6%) with TTA, and 547 (32.0%) with TAA (mostly transaxillary). Compared with TTA, both TFA (adjusted HR: 0.58; 95% CI: 0.45-0.75) and TAA (adjusted HR: 0.60; 95% CI: 0.47-0.78) were associated with lower 30-day rates of MAE, driven by fewer access site–related complications. Composite risks at 1 year were also lower with TFA and TAA compared with TTA. TFA compared with TAA was associated with lower 1-year risk of stroke/TIA (adjusted HR: 0.49; 95% CI: 0.24-0.98), a finding confined to patients with low Hostile scores (P interaction = 0.049). Among patients with PAD undergoing TAVR, both TFA and TAA were associated with lower 30-day and 1-year rates of MAE compared with TTA, but 1-year stroke/TIA rates were higher with TAA compared with TFA. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: Surgical aortic valve bioprostheses may degenerate over time and require redo intervention. Transcatheter aortic valve replacement (TAVR) is a less invasive alternative to redo surgery. The BAlloon Expandable vs. SElf Expanding Transcatheter VaLve for Degenerated BioprosthesIs (BASELINE) trial was designed to compare the performance of the balloon-expandable SAPIEN-3 Ultra and the self-expanding EVOLUT PRO+ valve systems in symptomatic patients with a failing surgical bioprosthesis.Methods: The BASELINE trial is an investigator-initiated, non-funded, prospective, randomized, open-label, superiority trial enrolling a total of 440 patients in up to 50 sites in 12 countries in Europe and North-America. The primary endpoint is device success at 30-days defined by the Valve Academic Research Consortium-3 Criteria as the composite of technical success, freedom from mortality, freedom for surgery or intervention related to the device or to a major vascular or access-related or cardiac structural complication with an intended performance of the valve (mean gradient <20 mmHg and less than moderate aortic regurgitation). The co-primary endpoint at 1 year is defined as the composite of all-cause death, disabling stroke, rehospitalization for heart failure or valve related problems. Independent Core Laboratories will conduct uniform analyses of echocardiography (pre-, post-, 1-year post-procedure), multi-sliced computed tomography (pre-, and if available post-procedure) and cine-fluoroscopy studies.Conclusions: The BASELINE trial is a head-to-head comparative trial investigating the two most used contemporary transcatheter heart valves for the treatment of a failing surgical aortic bioprosthesis. (ClinicalTrials.gov number NCT04843072). [ABSTRACT FROM AUTHOR]

New permanent pacemaker implantation (new-PPI) remains a compelling issue after Transcatheter Aortic Valve Replacement (TAVR). Previous studies reported the relationship between a short MS length and the new-PPI post-TAVR with a self-expanding THV. However, this relationship has not been investigated in different currently available THV. Therefore, the aim of this study was to investigate the association between membranous septum (MS)-length and new-PPI after TAVR with different Transcatheter Heart Valve (THV)-platforms. We included patients with a successful TAVR-procedure and an analyzable pre-procedural multi-slice computed tomography. MS-length was measured using a standardized methodology. The primary endpoint was the need for new-PPI within 30 days after TAVR. In total, 1811 patients were enrolled (median age 81.9 years [IQR 77.2–85.4], 54% male). PPI was required in 275 patients (15.2%) and included respectively 14.2%, 20.7% and 6.3% for Sapien3, Evolut and ACURATE-THV(p ​< ​0.01). Median MS-length was significantly shorter in patients with a new-PPI (3.7 ​mm [IQR 2.2–5.1] vs. 4.1 ​mm [IQR 2.8–6.0], p ​= ​<0.01). Shorter MS-length was a predictor for PPI in patients receiving a Sapien3 (OR 0.87 [95% CI 0.79–0.96], p ​= ​<0.01) and an Evolut-THV (OR 0.91 [95% CI 0.84–0.98], p ​= ​0.03), but not for an ACURATE-THV (OR 0.99 [95% CI 0.79–1.21], p ​= ​0.91). By multivariable analysis, first-degree atrioventricular-block (OR 2.01 [95% CI 1.35–3.00], p = <0.01), right bundle branch block (OR 8.33 [95% CI 5.21–13.33], p = <0.01), short MS-length (OR 0.89 [95% CI 0.83–0.97], p ​< ​0.01), annulus area (OR 1.003 [95% CI 1.001–1.005], p ​= ​0.04), NCC implantation depth (OR 1.13 [95% CI 1.07–1.19] and use of Evolut-THV(OR 1.54 [95% CI 1.03–2.27], p ​= ​0.04) were associated with new-PPI. MS length was an independent predictor for PPI across different THV platforms, except for the ACURATE-THV. Based on our study observations within the total cohort, we identified 3 risk groups by MS length: MS length ≤3 ​mm defined a high-risk group for PPI (>20%), MS length 3–7 ​mm intermediate risk for PPI (10–20%) and MS length > 7 ​mm defined a low risk for PPI (<10%). Anatomy-tailored-THV-selection may mitigate the need for new-PPI in patients undergoing TAVR. The aim of this study was to investigate the association between membranous septum (MS)-length and new-permanent pacemaker implantation (PPI) after transcatheter aortic valve replacement (TAVR) with different Transcatheter Heart Valve (THV)-platforms. 1811 patients with a successful TAVR-procedure and an analyzable multi-slice computed tomography were retrospectively included in this study. MS-length was measured using a standardized methodology. New-PPI occurred in 15.2% of the patients and the MS length was significantly shorter in patients receiving a new-PPI. In conclusion, MS length was an independent predictor for PPI across different THV platforms, except for the ACURATE-THV. Anatomy-tailored-THV-selection may mitigate the need for new-PPI in patients undergoing TAVR. [ABSTRACT FROM AUTHOR]

The present research letter reports the 1-year clinical outcomes of the randomized COMPARE CRUSH trial, which allocated STEMI patients at first medical contact in the ambulance to receive either crushed or integral tablets of prasugrel loading dose. This trial aimed to investigate whether early enhanced antiplatelet effect constituted by the crushed potent oral P2Y12 inhibitor prasugrel could lead to improved early myocardial reperfusion and clinical outcomes. [ABSTRACT FROM AUTHOR]

Transcatheter aortic valve replacement (TAVR) is increasingly being performed in younger and lower surgical risk patients. Given the longer life expectancy of these patients, the bioprosthetic valve will eventually fail, and aortic valve reintervention may be necessary. Although currently rare, redo-TAVR will likely increase in the future as younger patients are expected to outlive their transcatheter bioprosthesis. This review provides a contemporary overview of the indications, procedural planning, implantation technique, and outcomes of TAVR in failed transcatheter bioprosthetic aortic valves. [Display omitted] • Redo-TAVR will become more prevalent as TAVR is increasingly performed in younger patients with longer life expectancies. • A multitude of clinical and anatomical factors need to be meticulously evaluated to determine candidacy and the feasibility of redo-TAVR in patients with transcatheter valve failure. • Transcatheter heart valve selection, sizing, and the implantation technique remain under active investigation in redo-TAVR to minimize coronary obstruction risk while preserving access. • Lifetime management of patients with aortic valve disease, including the possibility of redo-TAVR versus TAVR explant, should be part of any heart team discussion. [ABSTRACT FROM AUTHOR]

Despite advances in transcatheter aortic valve replacement (TAVR), periprocedural acute ischemic stroke remains a concern. The aims of this study were to investigate acute ischemic stroke complicating TAVR (AISCT) and to describe the indications and outcomes of interventions to treat AISCT. An international multicenter registry was established focusing on AISCT within 30 days of TAVR. Stroke severity was assessed using the National Institutes of Health Stroke Scale. Primary outcomes were 1-year all-cause death and neurologic disability status at 90 days according to modified Rankin scale score. Of 16,615 TAVR procedures, 387 patients with AISCT were included (2.3%). Rates of 1-year death were 28.9%, 35.9%, and 77.5% in patients with mild, moderate, and severe stroke, respectively (P < 0.001). Although 348 patients were managed conservatively, 39 patients (10.1%) underwent neurointervention (NI) with either mechanical thrombectomy (n = 26) or thrombolytic therapy (n = 13). In a subanalysis excluding patients with mild stroke, there was no clear 1-year survival benefit for NI compared with conservative management (47.6% vs 41.1%, respectively; P = 0.78). In a logistic regression model controlling for stroke severity, NI was associated with 2.9-fold odds (95% CI: 1.2-7.0; P = 0.016) of independent survival at 90 days. AISCT carries significant morbidity and mortality, which is correlated with stroke severity. The present findings suggest that neurologic disability for patients with moderate or worse stroke could potentially be improved by timely intervention and highlight the importance of collaboration between cardiologists and neurologists to optimize AISCT outcomes. [Display omitted] [ABSTRACT FROM AUTHOR]

Post–percutaneous coronary intervention (PCI) fractional flow reserve (FFR) <0.90 is common and has been related to impaired patient outcome. The authors sought to evaluate if PCI optimization directed by intravascular ultrasound (IVUS) in patients with post-PCI FFR <0.90 could improve 1-year target vessel failure (TVF) rates. In this single-center, randomized, double-blind trial, patients with a post-PCI FFR <0.90 at the time of angiographically successful PCI were randomized to IVUS-guided optimization or the standard of care (control arm). The primary endpoint was TVF (a composite of cardiac death, spontaneous target vessel myocardial infarction, and clinically driven target vessel revascularization) at 1 year. A total of 291 patients with post-PCI FFR <0.90 were randomized (IVUS-guided optimization arm: n = 145/152 vessels, control arm: n = 146/157 vessels). The mean post-PCI FFR was 0.84 ± 0.05. A total of 104 (68.4%) vessels in the IVUS-guided optimization arm underwent additional optimization including additional stenting (34.9%) or postdilatation only (33.6%), resulting in a mean increase in post-PCI FFR in these vessels from 0.82 ± 0.06 to 0.85 ± 0.05 (P < 0.001) and a post-PCI FFR ≥0.90 in 20% of the vessels. The 1-year TVF rate was comparable between the 2 study arms (IVUS-guided optimization arm: 4.2%, control arm: 4.8%; P = 0.79). There was a trend toward a lower incidence of clinically driven target vessel revascularization in the IVUS-guided optimization arm (0.7% vs. 4.2%, P = 0.06). IVUS-guided post-PCI FFR optimization significantly improved post-PCI FFR. Because of lower-than-expected event rates, post-PCI FFR optimization did not significantly lower TVF at the 1-year follow-up. [Display omitted] [ABSTRACT FROM AUTHOR]

This study sought to evaluate patient-centered metrics in intermediate-surgical-risk aortic stenosis patients enrolled in the SURTAVI (Surgical Replacement and Transcatheter Aortic Valve Implantation) trial treated with self-expanding transcatheter aortic valve replacement (TAVR) or surgery. Studies have shown TAVR to be an alternative to surgery in patients with severe symptomatic aortic stenosis but have focused on "hard endpoints," including all-cause mortality and stroke, rather than on comparative patient-centered metrics, such as functional status and symptom burden. The study analyzed functional status (6-minute walk test [6MWT]) and symptom burden (Kansas City Cardiomyopathy Questionnaire) in 1,492 patients from the SURTAVI trial at baseline, 30 days, 1 year, and 2 years. Patients were categorized by baseline functional status into tertiles of slow, medium, and fast walkers. Patients with lowest capacity baseline functional status were commonly women, had higher Society of Thoracic Surgeons scores, and had more New York Heart Association functional class III or IV symptoms; reduced baseline functional status was associated with higher aortic valve– and heart failure–related hospitalization at 2 years. There was greater improvement in 6MWT distance in TAVR compared with surgery patients at 30 days (P < 0.001) and 1 year (P = 0.012), but at 2 years, both groups had similar improvement (P = 0.091). The percentage of patients with large improvement in 6MWT was greatest in patients categorized as slow walkers and lowest in fast walkers. Symptom burden improved after TAVR at 30 days and after both procedures at 1 and 2 years. In this substudy of patients from the SURTAVI trial, patients receiving TAVR demonstrated a more rapid improvement in functional status and symptom burden compared with patients undergoing surgery; however, both groups had similar improvements in long-term follow-up. (Safety and Efficacy Study of the Medtronic CoreValve® System in the Treatment of Severe, Symptomatic Aortic Stenosis in Intermediate Risk Subjects Who Need Aortic Valve Replacement [SURTAVI]; NCT01586910) [Display omitted] [ABSTRACT FROM AUTHOR]

This study evaluated the incidence, management, and outcome of patients who experienced MitraClip (Abbott Vascular) failure secondary to loss of leaflet insertion (LLI), single leaflet detachment (SLD), or embolization. Transcatheter edge-to-edge repair with MitraClip is an established therapy for the treatment of mitral regurgitation (MR), but no data exist regarding the prevalence and outcome according to the mode of clip failure. Between January 2009 and December 2020, we retrospectively screened 4,294 procedures of MitraClip performed in 19 centers. LLI was defined as damage to the leaflet where the MitraClip was attached, SLD as demonstration of complete separation between the device and a single leaflet tissue, and clip embolization as loss of contact between MitraClip and both leaflets. A total of 147 cases of MitraClip failure were detected (overall incidence = 3.5%), and these were secondary to LLI or SLD in 47 (31.9%) and 99 (67.3%) cases, respectively, whereas in 1 (0.8%) case clip embolization was observed. MitraClip failure occurred in 67 (45.5%) patients with functional MR, in 64 (43.5%) patients with degenerative MR, and 16 (10.8%) with mixed etiology. Although the majority of MitraClip failures were detected before discharge (47 intraprocedural and 42 in the hospital), up to 39.5% of cases were diagnosed at follow-up. In total, 80 (54.4%) subjects underwent a redo procedure, either percutaneously with MitraClip (n = 51, 34.7%) or surgically (n = 36, 24.5%) including 4 cases of surgical conversion of the index procedure and 7 cases of bailout surgery after unsuccessful redo MitraClip. After a median follow-up of 163 days (IQR: 22-720 days), 50 (43.9%) subjects presented moderate to severe MR, and 43 (29.3%) patients died. An up-front redo MitraClip strategy was associated with a trend toward a reduced rate of death at follow-up vs surgical or conservative management (P = 0.067), whereas postprocedural acute kidney injury, age, and moderate to severe tricuspid regurgitation were independent predictors of death. MitraClip failure secondary to LLI and SLD is not a rare phenomenon and may occur during and also beyond hospitalization. Redo MitraClip strategy demonstrates a trend toward a reduced risk of death compared with bailout surgery and conservative management. A third of those patients remained with more than moderate MR and had substantial mortality at the intermediate-term follow-up. [Display omitted] [ABSTRACT FROM AUTHOR]

Although clinical outcomes after percutaneous coronary intervention (PCI) are improving, the long-term risk for target vessel failure remains concerning. Although the application of intravascular imaging and physiological indexes significantly improves outcomes, their routine use in practice remains limited. Nevertheless, merely using these modalities is not enough, and to truly improve patient outcomes, optimal intravascular dimensions with minimal vascular injury should be targeted. When assessing post-PCI results using either type of physiological or imaging technology, a broad spectrum of stent- and vessel-related anomalies can be expected. As not all of these issues warrant treatment, a profound knowledge of what to expect and how to recognize and when to treat these intraluminal problems is needed. Additionally, promising new modalities such as angiography-derived coronary physiology and hybrid imaging catheters are becoming available. The authors provide an overview of the currently available tools and techniques to define suboptimal PCI and when to apply these technologies to improve outcomes. [Display omitted] • Target vessel failure following contemporary PCI remains concerning. • Both post PCI imaging and physiology often reveal key reasons for suboptimal PCI. • Recognizing and treating relevant residual intravascular pathology may improve outcome. [ABSTRACT FROM AUTHOR]

An increasing body of evidence suggests that packed red blood cell (PRBC) transfusion may be associated with increased morbidity and mortality after transcatheter and surgical aortic valve replacement. It remains unclear whether PRBC transfusion is a surrogate marker or truly an independent risk factor for mortality after aortic valve replacement in different populations. The Surgical Replacement and Transcatheter Aortic Valve Implantation (SURTAVI) trial randomized 1660 patients with symptomatic, severe aortic stenosis at intermediate risk for operative death to transcatheter aortic valve replacement or surgical aortic valve replacement. Baseline characteristics and outcomes including all-cause and cardiovascular mortality at 30 days and thereafter were compared between participants with and participants without PRBC transfusion. Cox proportional hazards models with time-varying covariates were fitted to estimate the effect of PRBC transfusion on mortality after adjustment for comorbidities and procedural complications. Patients receiving PRBC were older, more commonly female and frail, with more comorbidities. The Society of Thoracic Surgeons Predicted Risk of Mortality baseline score was higher in the transfused group. After adjustment for these differences, PRBC transfusion was associated with mortality at 30 days, but not thereafter. The effect of PRBC on mortality (hazard ratio 1.04; 95% confidence interval, 0.96 to 1.11; P =. 304) at 30 days was not independent of procedural complications (hazard ratio 21.04; 95% CI, 7.26 to 60.95; P <. 001). Poor health status, procedural complications, PRBC transfusion, and mortality are correlated with each other. Transfusion of PRBC did not independently increase risk for mortality. In this intermediate-risk population, transfusion appears to be a risk marker of chronic conditions and periprocedural complications as opposed to a risk factor for postprocedural mortality. (Clinical trial registration: www.clinicaltrials.gov NCT01586910.) [ABSTRACT FROM AUTHOR]

A plethora of catheter-based strategies have been developed to treat mitral valve disease. Evolving 3-dimensional (3D) multidetector computed tomography (MDCT) technology can accurately reconstruct the mitral valve by means of 3-dimensional computational modeling (3DCM) to allow virtual implantation of catheter-based devices. 3D printing complements computational modeling and offers implanting physician teams the opportunity to evaluate devices in life-size replicas of patient-specific cardiac anatomy. MDCT-derived 3D computational and 3D-printed modeling provides unprecedented insights to facilitate hands-on procedural planning, device training, and retrospective procedural evaluation. This overview summarizes current concepts and provides insight into the application of MDCT-derived 3DCM and 3D printing for the planning of transcatheter mitral valve replacement and closure of paravalvular leaks. Additionally, future directions in the development of 3DCM will be discussed. [Display omitted] • Catheter-based interventions for complex defects of the mitral valve apparatus are evolving. • MDCT-derived 3D computational modeling and 3D printing enhance risk evaluation and planning of complex transcatheter procedures. • Incorporation of multiple cardiac phases, tissue/device properties, and hemodynamics should optimize 3D modeling. [ABSTRACT FROM AUTHOR]

This study sought to compare the pharmacodynamic effects of pre-hospitally administered P2Y 12 inhibitor prasugrel in crushed versus integral tablet formulation in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (pPCI). Early dual antiplatelet therapy is recommended in STEMI patients. Yet, onset of oral P2Y 12 inhibitor effect is delayed and varies according to formulation administered. The COMPARE CRUSH (Comparison of Pre-hospital Crushed Versus Uncrushed Prasugrel Tablets in Patients With STEMI Undergoing Primary Percutaneous Coronary Interventions) trial randomized patients with suspected STEMI to crushed or integral prasugrel 60-mg loading dose in the ambulance. Pharmacodynamic measurements were performed at 4 time points: before antiplatelet treatment, at the beginning and end of pPCI, and 4 h after study treatment onset. The primary endpoint was high platelet reactivity at the end of pPCI. The secondary endpoint was impact of platelet reactivity status on markers of coronary reperfusion. A total of 441 patients were included. In patients with crushed prasugrel, the occurrence of high platelet reactivity at the end of pPCI was reduced by almost one-half (crushed 34.7% vs. uncrushed 61.6%; odds ratio [OR] = 0.33; 95% confidence interval [CI] = 0.22 to 0.50; p < 0.01). Platelet reactivity <150 P2Y 12 reactivity units at the beginning of coronary angiography correlated with improved Thrombolysis In Myocardial Infarction flow grade 3 in the infarct artery pre-pPCI (OR: 1.78; 95% CI: 1.08 to 2.94; p = 0.02) but not ST-segment resolution (OR: 0.80; 95% CI: 0.48 to 1.34; p = 0.40). Oral administration of crushed compared with integral prasugrel significantly improves platelet inhibition during the acute phase in STEMI patients undergoing pPCI. However, a considerable number of patients still exhibit inadequate platelet inhibition at the end of pPCI, suggesting the need for alternative agents to bridge the gap in platelet inhibition. [Display omitted] [ABSTRACT FROM AUTHOR]

The aim of this study was to define predictors of prosthesis-patient mismatch (PPM) and its impact on mortality after transcatheter aortic valve replacement (TAVR) with self-expandable valves (SEVs) in patients with small annuli. TAVR seems to reduce the risk for PPM compared with surgical aortic valve replacement, especially in patients with small aortic annuli. Nevertheless, predictors and impact of PPM in this population have not been clarified yet. Predictors of PPM and all-cause mortality were investigated using multivariable logistic regression analysis from the cohort of the TAVI-SMALL (International Multicenter Registry to Evaluate the Performance of Self-Expandable Valves in Small Aortic Annuli) registry, which included patients with severe aortic stenosis and small annuli (annular perimeter <72 mm or area <400 mm2 on computed tomography) treated with transcatheter SEVs: 445 patients with (n = 129) and without (n = 316) PPM were enrolled. Intra-annular valves conferred increased risk for PPM (odds ratio [OR]: 2.36; 95% confidence interval [CI]: 1.16 to 4.81), while post-dilation (OR: 0.46; 95% CI: 0.25–0.84) and valve oversizing (OR: 0.53; 95% CI: 0.28–1.00) seemed to protect against PPM occurrence. At a median follow-up of 354 days, patients with severe PPM, but not those with moderate PPM, had a higher all-cause mortality rate compared with those without PPM (log-rank p = 0.008). Multivariable Cox regression confirmed severe PPM as an independent predictor of all-cause mortality (hazard ratio: 4.27; 95% CI: 1.34 to 13.6). Among patients with aortic stenosis and small aortic annuli undergoing transcatheter SEV implantation, use of intra-annular valves yielded higher risk for PPM; conversely, post-dilation and valve oversizing protected against PPM occurrence. Severe PPM was independently associated with all-cause mortality. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: The study investigators previously reported that moderate aortic stenosis (AS) is associated with a poor prognosis in patients with heart failure (HF) with reduced left ventricular ejection fraction (LVEF) (HFrEF). However, the respective contribution of moderate AS versus HFrEF to the outcomes of these patients is unknown.Objectives: This study sought to determine the impact of moderate AS on outcomes in patients with HFrEF.Methods: The study included 262 patients with moderate AS (aortic valve area >1.0 and <1.5 cm2; and peak aortic jet velocity >2 and <4 m/s, at rest or after dobutamine stress echocardiography) and HFrEF (LVEF <50%). These patients were matched 1:1 for sex, age, estimated glomerular filtration rate, New York Heart Association functional class III to IV, presence of diabetes, LVEF, and body mass index with patients with HFrEF but no AS (i.e., peak aortic jet velocity <2 m/s). The endpoints were all-cause mortality and the composite of death and HF hospitalization.Results: A total of 262 patients with HFrEF and moderate AS were matched with 262 patients with HFrEF and no AS. Mean follow-up was 2.9 ± 2.2 years. In the moderate AS group, mean aortic valve area was 1.2 ± 0.2 cm2, and mean gradient was 14.5 ± 4.7 mm Hg. Moderate AS was associated with an increased risk of mortality (hazard ratio [HR]: 2.98; 95% confidence interval [CI]: 2.08 to 4.31; p < 0.0001) and of the composite of HF hospitalization and mortality (HR: 2.34; 95% CI: 1. 72 to 3.21; p < 0.0001). In the moderate AS group, aortic valve replacement (AVR) performed in 44 patients at a median follow-up time of 10.9 ± 16 months during follow-up was associated with improved survival (HR: 0.59; 95% CI: 0.35 to 0.98; p = 0.04). Notably, surgical AVR was not significantly associated with improved survival (p = 0.92), whereas transcatheter AVR was (HR: 0.43; 95% CI: 0.18 to 1.00; p = 0.05).Conclusions: In this series of patients with HFrEF, moderate AS was associated with a marked incremental risk of mortality. AVR, and especially transcatheter AVR during follow-up, was associated with improved survival in patients with HFrEF and moderate AS. These findings provide support to the realization of a randomized trial to assess the effect of early transcatheter AVR in patients with HFrEF and moderate AS. [ABSTRACT FROM AUTHOR]

[Display omitted] [ABSTRACT FROM AUTHOR]

• Ninety percent of patients naïve to revascularization prefer percutaneous coronary intervention (PCI) over coronary artery bypass grafting (CABG). • Patients opting for PCI value lower short-term morbidity over long-term re-PCI risk. • CABG preference was most common in lower educated patients. • Educational and psychosocial background matter in the decision-making process. Treatment preferences in patients with left main (LM) stem disease and no prior revascularization are unknown. The objectives of this study were to determine (i) patient-reported importance ratings of particular features related to percutaneous coronary intervention (PCI) and coronary artery bypass graft (CABG) surgery, (ii) how these features determine treatment preference, and (iii) how educational and psychosocial background influence this preference. In this prospective, multicenter study a total of 500 patients without previous revascularization who underwent diagnostic angiography for suspected coronary disease were asked to complete a case-vignette on a (hypothetical) LM stenosis qualifying for both PCI and CABG, in addition to 6 validated questionnaires to assess the influence of psychosocial factors on treatment preference. Overall, 90% favored PCI over CABG because of the lower bleeding and stroke risk despite a higher likelihood for repeat revascularization. By multivariable regression, the only independent determinant of treatment preference for CABG was lower educational level (14% in low vs. 8% in higher educated patients, OR: 3.22, CI: 1.16–8.95, p = 0.025) while psychosocial variables were not associated. Compared to higher educated patients, those with lower educational level suffered more from depression, anxiety, loneliness, and uncertainty. Overall, patients who are informed about risk and benefits of each treatment modality clearly favor PCI over CABG and particularly value lower short-term morbidity while being aware of higher risk of repeat revascularization. Lower educational level was associated with a higher prevalence of psychosomatic phenotypes and a 14% preference for CABG. Educational and psychosocial background matter in the revascularization strategy decision-making process. [ABSTRACT FROM AUTHOR]

This study sought to test the superiority in terms of efficacy and safety of a dedicated plug-based vascular closure device (VCD) during transcatheter aortic valve replacement (TAVR) over a suture-based VCD. Vascular complications after TAVR are relevant and often associated with VCD failure. The MASH (MANTA vs. Suture-based vascular closure after transcatHeter aortic valve replacement) trial is an international, 2-center pilot randomized controlled trial comparing the MANTA VCD (Teleflex, Wayne, Pennsylvania) versus 2 ProGlides (Abbott Vascular, Abbott Park, Illinois). The primary composite endpoint consisted of access site–related major or minor vascular complications at 30-days' follow-up. Secondary endpoints included clinically relevant access site bleeding, time to hemostasis, and modified VCD failure (defined as failure to achieve hemostasis within 5 min or requiring additional endovascular maneuvers such as endovascular stenting, surgical techniques, or additional closure devices). Adverse events were adjudicated by an independent clinical events committee according to the VARC-2 definitions. A total of 210 TAVR patients were included between October 2018 and January 2020. Median age was 81 years, 54% were male, and the median STS score was 2.7%. There was no significant difference in the primary endpoint of access site–related vascular complications between MANTA and ProGlide (10% vs. 4%; p = 0.16). Clinically significant access site bleedings were similar with both closure techniques (9% vs. 6%; p = 0.57). Modified VCD failure occurred less frequently in MANTA versus ProGlide (20% vs. 40%; p < 0.01). Suture-based closure required more often additional closure devices, whereas MANTA numerically needed more covered stents and surgical bailouts. Plug-based large-bore arteriotomy closure was not superior to suture-based closure. Plug-based closure required fewer, but a different kind of bailout maneuvers. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the short-term safety and efficacy of transcatheter aortic valve replacement (TAVR) with the LOTUS Edge system. The LOTUS Edge system was commercially re-released in April 2019. The authors report the first European experience with this device. A multicenter, single-arm, retrospective registry was initiated to evaluate short-term clinical outcomes. Included cases are the first experience with this device and new implantation technique in Europe. Clinical, echocardiographic, and computed tomographic data were analyzed. Endpoints were defined according to Valve Academic Research Consortium-2 and were site reported. Between April and November 2019, 286 consecutive patients undergoing TAVR with the LOTUS Edge system at 18 European centers were included. The mean age and Society of Thoracic Surgeons score were 81.2 ± 6.9 years and 5.2 ± 5.4%, respectively. Nearly one-half of all patients (47.9%) were considered to have complex anatomy. Thirty-day major adverse events included death (2.4% [n = 7]) and stroke (3.5% [n = 10]). After TAVR, the mean aortic valve area was 1.9 ± 0.9 cm2, and the mean transvalvular gradient was 11.9 ± 5.7 mm Hg. None or trace paravalvular leak (PVL) occurred in 84.4% and moderate PVL in 2.0%. There were no cases of severe PVL. New permanent pacemaker (PPM) implantation was required in 25.9% among all patients and 30.8% among PPM-naive patients. Early experience with the LOTUS Edge system demonstrated satisfactory short-term safety and efficacy, favorable hemodynamic data, and very low rates of PVL in an anatomically complex cohort. New PPM implantation remained high. Further study will evaluate if increasing operator experience with the device and new implantation technique can reduce the incidence of PPM implantation. [ABSTRACT FROM AUTHOR]

Background: Complete revascularization in patients with an acute coronary syndrome and multivessel disease is superior compared to culprit-only treatment. However, it is unknown whether direct complete or staged complete revascularization should be pursued.Methods: The BIOVASC study is an investigator-initiated, prospective, multicenter, randomized, 2-arm, international, open-label, noninferiority trial. We will randomize 1,525 patients 1:1 to immediate complete revascularization (experimental arm) or culprit-only plus staged complete revascularization (control arm). Patients will be enrolled in approximately 30 sites in Belgium, Italy, the Netherlands, and Spain. The primary end point is a composite of all-cause mortality, nonfatal myocardial infarction, any unplanned ischemia-driven revascularization (excluding staged procedures in the control arm at the predetermined time), and cerebrovascular events (MACCE) at 1 year post index procedure.Conclusions: The BIOVASC study aims to further refine the treatment algorithm for acute coronary syndrome patients with multivessel disease in terms of optimal timing for complete revascularization (Clinicaltrials.gov NCT03621501). [ABSTRACT FROM AUTHOR]

Background: Dual antiplatelet therapy constitutes the cornerstone of medical treatment in patients with ST elevation myocardial infarction (STEMI). However, oral antiplatelet agents, such as prasugrel or ticagrelor, are characterized by slow gastrointestinal drug absorption in the acute phase of STEMI, leading to decreased bioavailability and therefore delayed onset of platelet inhibition. Evidence suggests that administration of crushed tablets of the P2Y12 inhibitor prasugrel improves drug absorption and achieves earlier antiplatelet effects in STEMI patients undergoing primary percutaneous coronary intervention (PCI). However, the clinical implications of these pharmacokinetic and pharmacodynamic findings are unknown.Hypothesis: The present study is designed to test the hypothesis that patients presenting with STEMI planned for primary PCI will have improved markers of optimal reperfusion and clinical outcomes by prehospital administration of crushed tablets of prasugrel loading dose.Study Design: COMPARE CRUSH (NCT03296540) is a randomized trial in a regionally organized ambulance care setting evaluating the efficacy and safety of pre-hospital loading dose with prasugrel crushed tablets versus integral tablets in approximately 674 patients presenting with STEMI planned for primary PCI. The independent primary endpoints are percentage of patients reaching thrombolysis in myocardial infarction (TIMI) flow grade 3 in the infarct-related artery at initial angiography, or achieving ≥70% ST-segment elevation resolution at 1 hour post-PCI. Secondary clinical endpoints are death, myocardial infarction, revascularization, and stent thrombosis followed up to 1 year. Moreover, the primary safety endpoint is bleeding events assessed at 48 hours.Conclusions: The COMPARE CRUSH trial will assess whether prehospital administration of loading dose prasugrel in form of crushed tablets - which is expected to provide faster platelet inhibition compared to standard treatment with integral tablets - results in improved reperfusion and clinical outcomes. RCT# NCT03296540. [ABSTRACT FROM AUTHOR]