Reduction of contrast medium for transcatheter aortic valve replacement planning using a spectral detector CT: a prospective clinical trial.

INTRODUCTION: This study investigated the use of dual-energy spectral detector computed tomography (CT) and virtual monoenergetic imaging (VMI) reconstructions in pre-interventional transcatheter aortic valve replacement (TAVR) planning. We aimed to determine the minimum required contrast medium (CM) amount to maintain diagnostic CT imaging quality for TAVR planning. METHODS: In this prospective clinical trial, TAVR candidates received a standardized dual-layer spectral detector CT protocol. The CM amount (Iohexol 350 mg iodine/mL, standardized flow rate 3 mL/s) was reduced systematically after 15 patients by 10 mL, starting at 60 mL (institutional standard). We evaluated standard, and 40- and 60-keV VMI reconstructions. For image quality, we measured signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and diameters in multiple vessel sections (i.e., aortic annulus: diameter, perimeter, area; aorta/arteries: minimal diameter). Mixed regression models (MRM), including interaction terms and clinical characteristics, were used for comparison. RESULTS: Sixty consecutive patients (mean age, 79.4 ± 7.5 years; 28 females, 46.7%) were included. In pre-TAVR CT, the CM reduction to 40 mL is possible without affecting the image quality (MRM: SNR: -1.1, p = 0.726; CNR: 0.0, p = 0.999). VMI 40-keV reconstructions showed better results than standard reconstructions with significantly higher SNR (+ 6.04, p < 0.001). Reduction to 30 mL CM resulted in a significant loss of quality (MRM: SNR: -12.9, p < 0.001; CNR: -13.9, p < 0.001), regardless of the reconstruction. Across the reconstructions, we observed no differences in the metric evaluation (p > 0.914). CONCLUSION: Among TAVR candidates undergoing pre-interventional CT at a dual-layer spectral detector system, applying 40 mL CM is sufficient to maintain diagnostic image quality. VMI 40-keV reconstructions improve the vessel attenuation and are recommended for evaluation. CLINICAL RELEVANCE STATEMENT: Contrast medium reduction to 40 mL in pre-interventional transcatheter aortic valve replacement CT using dual-energy CT maintains image quality, while 40-keV virtual monoenergetic imaging reconstructions enhance vessel attenuation. These results offer valuable recommendations for interventional transcatheter aortic valve replacement evaluation and potentially improve nephroprotection in patients with compromised renal function. KEY POINTS: • Patients undergoing transcatheter aortic valve replacement (TAVR), requiring pre-interventional CT, are often multimorbid with impaired renal function. • Using a spectral detector dual-layer CT, contrast medium reduction to 40 mL is feasible, maintaining diagnostic image quality. • The additional application of virtual monoenergetic image reconstructions with 40 keV improves vessel attenuation significantly in clinical practice.

Surgical Versus Interventional Treatment of Major Access Site Complications During Transfemoral TAVI Procedures at a Large Volume Center.

PURPOSE: Access-related vascular complications in transfemoral transcatheter aortic valve implantation (TAVI) can be treated endovascularly or surgically. The aim of this study was to evaluate the short- and long-term outcomes of endovascular treatment compared with surgical repair for access-related vascular complications. METHODS: This retrospective study was performed from January 1, 2018, to December 31, 2020. All transfemorally treated TAVI patients in whom a surgical or endovascular treatment for an access site complication was needed were included. The primary outcome was the need for any related vascular re-operation. RESULTS: In total, 1219 transfemoral TAVI procedures were conducted during the study period. 19 patients suffered an access complication requiring endovascular treatment, while 54 patients required surgical repair. No differences were seen with regard to re-operations (endovascular 15.8% vs surgical 14.8%; p=0.919), wound infections (endovascular 0% vs surgical. 11.1%; p=0.129), and wound healing disorders (endovascular 15.8% vs surgical 29.6%; p=0.237). Patients undergoing endovascular treatment were discharged earlier (endovascular 11.2 vs surgical 14.9 days; p=0.028). After surgical repair, patients received significantly more blood transfusions than endovascularly treated patients (endovascular 1.00 vs surgical 3.1 red blood cell concentrate bags; p<0.001). No differences were found regarding the new onset of walking pain, rest pain, and ischemic ulcers during follow-up. CONCLUSION: In this retrospective cohort, endovascular treatment of access-related vascular complications of transfemoral TAVI procedures was safe and feasible. During the hospital stay, endovascularly treated patients received fewer blood transfusions and were discharged faster than surgically treated patients. No differences regarding clinical outcomes and re-intervention rates were seen during the follow-up. CLINICAL IMPACT: Given the in this retrospective study demonstrated safety and feasibility of endovascular treatment for major access-related vascular complications, along with the in-hospital benefits and absence of follow-up disadvantages compared to surgical treatment, endovascular treatment should be considered in cases of major access-related vascular complications in transfemoral TAVI patients.

Myeloperoxidase is a critical mediator of anthracycline-induced cardiomyopathy.

Cardiotoxicity is a major complication of anthracycline therapy that negatively impacts prognosis. Effective pharmacotherapies for prevention of anthracycline-induced cardiomyopathy (AICM) are currently lacking. Increased plasma levels of the neutrophil-derived enzyme myeloperoxidase (MPO) predict occurrence of AICM in humans. We hypothesized that MPO release causally contributes to AICM. Mice intravenously injected with the anthracycline doxorubicin (DOX) exhibited higher neutrophil counts and MPO levels in the circulation and cardiac tissue compared to saline (NaCl)-treated controls. Neutrophil-like HL-60 cells exhibited increased MPO release upon exposition to DOX. DOX induced extensive nitrosative stress in cardiac tissue alongside with increased carbonylation of sarcomeric proteins in wildtype but not in Mpo-/- mice. Accordingly, co-treatment of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) with DOX and MPO aggravated loss of hiPSC-CM-contractility compared to DOX treatment alone. DOX-treated animals exhibited pronounced cardiac apoptosis and inflammation, which was attenuated in MPO-deficient animals. Finally, genetic MPO deficiency and pharmacological MPO inhibition protected mice from the development of AICM. The anticancer efficacy of DOX was unaffected by MPO deficiency. Herein we identify MPO as a critical mediator of AICM. We demonstrate that DOX induces cardiac neutrophil infiltration and release of MPO, which directly impairs cardiac contractility through promoting oxidation of sarcomeric proteins, cardiac inflammation and cardiomyocyte apoptosis. MPO thus emerges as a promising pharmacological target for prevention of AICM.

Transcatheter Aortic Valve Replacement for Isolated Aortic Regurgitation Using a New Self-Expanding TAVR System.

BACKGROUND: Patients with severe aortic regurgitation (AR) are often not considered for surgery because of increased surgical risk. Because of unique anatomical characteristics among patients with AR, interventional treatment options are limited, and implantation results are inconsistent compared with those among patients with aortic stenosis. OBJECTIVES: The authors describe the initial commercial experience of the first Conformité Européenne-marked transfemoral transcatheter aortic valve replacement system (JenaValve Trilogy [JV]) for the treatment of patients with AR. METHODS: This multicenter registry included 58 consecutive patients from 6 centers across Germany. Transcatheter aortic valve replacement was performed with the JV system for isolated severe and symptomatic AR. Patient characteristics, primary implantation outcomes, and valve performance up to 30 days were analyzed using Valve Academic Research Consortium 3 definitions. RESULTS: The mean patient age was 76.5 ± 9 years, with a mean Society of Thoracic Surgeons score of 4.2% ± 4.3%. Device success was achieved in 98% of patients. The mean gradient was 4.3 ± 1.6 mm Hg, and no moderate or severe paravalvular regurgitation occurred. No conversion to open heart surgery or valve embolization was reported. There were no major vascular complications or bleeding events. The rate of new permanent pacemaker implantation was 19.6%. At 30 days, 92% of the patients were in NYHA functional class I or II, and the 30-day mortality rate was 1.7%. CONCLUSIONS: Treatment of patients with severe symptomatic AR using the transfemoral JV system is safe and effective. Given its favorable hemodynamic performance and low complication rates, this system may offer a new treatment option for patients with AR not suitable for surgery.

Left ventricular reverse remodeling after transcatheter aortic valve implantation in patients with low-flow low-gradient aortic stenosis.

OBJECTIVES: Left ventricular reverse remodeling (LVRR) is associated with improved outcome in patients with heart failure. Factors associated with and predictive of LVRR in patients with low-flow low-gradient aortic stenosis (LFLG AS) after transcatheter aortic valve implantation (TAVI) and its impact on outcome were assessed. METHODS: Pre- and postprocedural left ventricular (LV) function and volume were investigated in 219 patients with LFLG. LVRR was defined as an absolute increase of ≥10% in LV ejection fraction (LVEF) and reduction of ≥15% in LV end-systolic volume (LVESV). The primary endpoint was the combination of all-cause mortality and rehospitalization for heart failure. RESULTS: The mean LVEF was 35.0 ± 10.0%, with a stroke volume index (SVI) of 25.9 ± 6.0 mL/m2 and LVESV of 94.04 ± 46.0 mL. At a median of 5.2 months (interquartile range, 2.7-8.1 months), 77.2% (n = 169) of the patients showed echocardiographic evidence of LVRR. A multivariate model revealed three independent factors for LVRR after TAVI: SVI of <25 mL/m2 (hazard ratio [HR], 2.31; 95% confidence interval [CI], 1.08-3.58; p < 0.01), LVEF of <30% (HR, 2.76; 95% CI, 1.53-2.91; p < 0.01), and valvulo-arterial impedance (Zva) of <5 mmHg/mL/m2 (HR, 5.36; 95% CI, 1.80-15.98; p < 0.01). Patients without evidence of LVRR showed a significantly higher incidence of the 1-year combined endpoint (32 [64.0%] vs. 75 [44.4%], p < 0.01). CONCLUSIONS: The majority of patients with LFLG AS show LVRR after TAVI, which is associated with favorable outcomes. An SVI of <25 mL/m2, LVEF of <30%, and Zva < 5mmHg/mL/m2 represent predictors of LVRR.

Toll-like receptor-3 contributes to the development of aortic valve stenosis.

Aortic valve stenosis (AS) development is driven by distinct molecular and cellular mechanisms which include inflammatory pathways. Toll-like-receptor-3 (TLR3) is a lysosomal pattern-recognition receptor that binds double-stranded RNA and promotes pro-inflammatory cellular responses. In recent years, TLR3 has emerged as a major regulator of vascular inflammation. The exact role of TLR3 in the development of AS has not been investigated. Isolated human valvular interstitial cells (VICs) were stimulated with the TLR3-agonist polyIC and the resulting pro-inflammatory and pro-osteogenic response measured. Severe AS was induced in wildtype- and TLR3-/- mice via mechanical injury of the aortic valve with a coronary springwire. TLR3 activation was achieved by polyIC injection every 24 h after wire injury, while TLR3 inhibition was realized using Compound 4a (C4a) every 48 h after surgery. Endothelial mesenchymal transition (EndoMT) of human valvular endothelial cells (VECs) was assessed after polyIC stimulation. Stimulation of human VICs with polyIC promoted a strong inflammatory and pro-osteogenic reaction. Similarly, injection of polyIC marginally increased AS development in mice after wire injury. AS induction was significantly decreased in TLR3-/- mice, confirming the role of endogenous TLR3 ligands in AS pathology. Pharmacological inhibition of TLR3 with C4a not only prevented the upregulation of inflammatory cytokines and osteogenic markers in VICs, and EndoMT in VECs, but also significantly abolished the development of AS in vivo. Endogenous TLR3 activation significantly contributes to AS development in mice. Pharmacological inhibition of TLR3 with C4a prevented AS formation. Therefore, targeting TLR3 may be a viable treatment option.

Prognostic impact of resting full-cycle ratio and diastolic non-hyperemic pressure ratios in patients with deferred revascularization.

BACKGROUND: Non-hyperemic pressure ratios (NHPRs) like resting full-cycle ratio (RFR), diastolic pressure ratio during entire diastole (dPR[entire]) and diastolic pressure ratio during wave-free period (dPR[WFP]) are increasingly used to guide revascularization. The effect of NHPRs on mid-term prognosis has not been well established. OBJECTIVE: We investigated the prognostic implications of NHRPs in patients whose revascularization was deferred based on fractional flow reserve (FFR) in a single-centre population. METHODS: NHPRs and FFR were calculated offline from pressure tracings by an independent core laboratory. Follow-up data were acquired through records of hospital visits or telephone interviews. The primary outcome was a vessel-oriented composite outcome (VOCO) (a composite of cardiac death, vessel-related myocardial infarction, and ischemia-driven revascularization) in deferred vessels at 2 years. RESULTS: 316 patients with 377 deferred lesions were analysed. Discordance of NHPRs and FFR was found in 13.0-18.3% of lesions. The correlation coefficient between NHPRs was 0.99 (95% confidence interval 0.99-1.00). At 2 years, VOCO occurred in 19 lesions (5.0%). Estimated glomerular filtration rate < 30 mL/min/1.73 m2 [hazard ratio (HR) 5.7, p = 0.002], previous myocardial infarction (HR 3.3, p = 0.018), diabetes (HR 2.7, p = 0.042), RFR ≤ 0.89 (HR 2.7, p = 0.041) and dPR[WFP] ≤ 0.89 (HR 2.7, p = 0.049) were associated with higher incidence of VOCO at 2 years in the univariable analysis. A non-significant trend was found for dPR[entire] (HR 1.9, p = 0.26). CONCLUSION: A positive RFR or dPR[WFP] were associated with a worse prognosis in deferred lesions, suggesting that the use of NHPRs in addition to FFR may improve risk estimation.

Transcatheter aortic valve implantation with different self-expanding devices-a propensity score-matched multicenter comparison.

OBJECTIVE: Several supra-annular self-expanding transcatheter systems are commercially available for transcatheter aortic valve implantation (TAVI). Comparative data in large-scale multicenter studies are scant. METHODS: This study included a total of 5175 patients with severe aortic stenosis undergoing TAVI with the ACURATE neo (n = 1095), Evolut R (n = 3365), or Evolut PRO (n = 715) by a transfemoral approach at five high-volume centers. Propensity score matching resulted in 654 triplets. Outcomes are reported according to the Valve Academic Research Consortium-3 (VARC-3) consensus. RESULTS: Moderate or severe paravalvular regurgitation (PVR) occurred significantly more often in the ACURATE neo group (5.2%) than in the Evolut R (1.8%) and Evolut PRO (3.3%) groups (p = 0.003). The rates of major vascular-/access-related complications (4.6%, 3.8%, and 5.0%; p = 0.56), type 3 or 4 bleeding (3.2%, 2.1%, and 4.1%; p = 0.12), and 30-day mortality (2.4%, 2.6%, and 3.7%; p = 0.40) were comparable. The rate of new permanent pacemaker implantation (PPI) was significantly lower in the ACURATE neo group (9.5%, 17.6%, and 16.8%; p < 0.001). Independent predictors for 2-year survival were a Society of Thoracic Surgeons (STS) risk score ≥5%, diabetes mellitus, a glomerular filtration rate <30 ml/min, baseline mean transvalvular gradient ≤ 30 mm Hg, treating center, and relevant PVR. CONCLUSION: In this multicenter study, TAVI with the ACURATE neo, Evolut R, or Evolut PRO was feasible and safe. The rate of relevant PVR was more frequent after the ACURATE neo implantation, with, however, lower rates of PPI. Two-year survival was mainly driven by baseline comorbidities.

E-cigarette exposure augments murine abdominal aortic aneurysm development: role of Chil1.

AIMS: Abdominal aortic aneurysm (AAA) is a common cardiovascular disease with a strong correlation to smoking, although underlying mechanisms have been minimally explored. Electronic cigarettes (e-cigs) have gained recent broad popularity and can deliver nicotine at comparable levels to tobacco cigarettes, but effects on AAA development are unknown. METHODS AND RESULTS: We evaluated the impact of daily e-cig vaping with nicotine on AAA using two complementary murine models and found that exposure enhanced aneurysm development in both models and genders. E-cigs induced changes in key mediators of AAA development including cytokine chitinase-3-like protein 1 (CHI3L1/Chil1) and its targeting microRNA-24 (miR-24). We show that nicotine triggers inflammatory signalling and reactive oxygen species while modulating miR-24 and CHI3L1/Chil1 in vitro and that Chil1 is crucial to e-cig-augmented aneurysm formation using a knockout model. CONCLUSIONS: In conclusion our work shows increased aneurysm formation along with augmented vascular inflammation in response to e-cig exposure with nicotine. Further, we identify Chil1 as a key mediator in this context. Our data raise concerns regarding the potentially harmful long-term effects of e-cig nicotine vaping.

Surgical versus Interventional Treatment of Concomitant Aortic Valve Stenosis and Coronary Artery Disease.

BACKGROUND: Coronary artery disease (CAD) is frequently diagnosed in patients with aortic valve stenosis. Treatment options include surgical and interventional approaches. We therefore analyzed short-term outcomes of patients undergoing either coronary artery bypass grafting with simultaneous aortic valve replacement (CABG + AVR) or staged percutaneous coronary intervention and transcatheter aortic valve implantation (PCI + TAVI). METHODS: From all patients treated since 2017, we retrospectively identified 237 patients undergoing TAVI within 6 months after PCI and 241 patients undergoing combined CABG + AVR surgery. Propensity score matching was performed, resulting in 101 matched pairs. RESULTS: Patients in the CABG + AVR group were younger compared with patients in the PCI + TAVI group (71.9 ± 4.9 vs 81.4 ± 3.6 years; p < 0.001). The overall mortality at 30 days before matching was higher after CABG + AVR than after PCI + TAVI (7.8 vs 2.1%; p = 0.012). The paired cohort was balanced for both groups regarding demographic variables and the risk profile (age: 77.2 ± 3.7 vs78.5 ± 2.7 years; p = 0.141) and EuroSCORE II (6.2 vs 7.6%; p = 0.297). At 30 days, mortality was 4.9% in the CABG + AVR group and 1.0% in the PCI + TAVI group (p = 0.099). Rethoracotomy was necessary in 7.9% in the CABG + AVR, while conversion to open heart surgery was necessary in 2% in the PCI + TAVI group. The need for new pacemaker was lower after CABG + AVR than after PCI + TAVI (4.1 vs 6.9%; p = 0.010). No paravalvular leak (PVL) was noted in the CABG + AVR group, while the incidence of moderate-to-severe PVL after PCI + TAVI was 4.9% (p = 0.027). CONCLUSION: A staged interventional approach comprises a short-term survival advantage compared with combined surgery for management of CAD and aortic stenosis. However, PCI + TAVI show a significantly higher risk of atrioventricular block and PVL. Further long-term trials are warranted.

Outcomes and Characteristics of Patients with Intraprocedural Cardiopulmonary Resuscitation during TAVR.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) has become an established alternative to surgical aortic valve replacement (AVR) for higher risk patients. Periprocedural TAVR complications decreased with a growing expertise of implanters. Yet, TAVR can be accompanied by life-threatening adverse events such as intraprocedural cardiopulmonary resuscitation (CPR). This study retrospectively analyzed predictors and outcomes in a cohort of patients from a high-volume center undergoing periprocedural CPR during TAVR. METHODS: A total of 729 patients undergoing TAVR, including 59 with intraprocedural CPR, were analyzed with respect to peri- and postprocedural outcomes. RESULTS: Patients undergoing CPR showed a significantly lower left ventricular ejection fraction (LVEF) and lower baseline transvalvular mean and peak pressure gradients. The systolic blood pressure measured directly preoperatively was significantly lower in the CPR cohort. CPR patients were in a higher need for intraprocedural defibrillation, heart-lung circulatory support, and conversion to open heart surgery. Further, they showed a higher incidence of atrioventricular block grade III , valve malpositioning, and pericardial tamponade. The in-hospital mortality was significantly higher after intraprocedural CPR, accompanied by a higher incidence of disabling stroke, new pacemaker implantation, more red blood cell transfusion, and longer stay in intensive care unit. CONCLUSION: Impaired preoperative LVEF and instable hemodynamics before valve deployment are independent risk factors for CPR and are associated with compromised outcomes. Heart rhythm disturbances, malpositioning of the prosthesis, and pericardial tamponade are main causes of the high mortality of 17% reported in the CPR group. Nevertheless, mechanical circulatory support and conversion to open heart surgery reduce mortality rates of CPR patients.

Valve-in-Valve TAVR versus Redo Surgical Aortic Valve Replacement: Early Outcomes.

OBJECTIVE: This study aimed to assess short-term outcomes of patients with failed aortic valve bioprosthesis undergoing valve-in-valve transcatheter aortic valve replacement (ViV-TAVR) or redo surgical aortic valve replacement (rSAVR). METHODS: Between 2009 and 2019, 90 patients who underwent ViV-TAVR (n = 73) or rSAVR (n = 17) due to failed aortic valve bioprosthesis fulfilled the inclusion criteria. Groups were compared regarding clinical end points, including in-hospital all-cause mortality. Patients with endocarditis and in a need of combined cardiac surgery were excluded from the study. RESULTS: ViV-TAVR patients were older (78.0 ± 7.4 vs. 62.1 ± 16.2 years, p = 0.012) and showed a higher prevalence of baseline comorbidities such as atrial fibrillation, diabetes mellitus, hyperlipidemia, and arterial hypertension. In-hospital all-cause mortality was higher for rSAVR than in the ViV-TAVR group (17.6 vs. 0%, p < 0.001), whereas intensive care unit stay was more often complicated by blood transfusions for rSAVR patients without differences in cerebrovascular events. The paravalvular leak was detected in 52.1% ViV-TAVR patients compared with 0% among rSAVR patients (p < 0.001). CONCLUSION: ViV-TAVR can be a safe and feasible alternative treatment option in patients with degenerated aortic valve bioprosthesis. The choice of treatment should include the patient's individual characteristics considering ViV-TAVR as a standard of care.

Contemporary treatment of mitral valve disease with transcatheter mitral valve implantation.

BACKGROUND: Transcatheter mitral valve implantation (TMVI) with self-expanding (SAV) or balloon-expandable (BAV) valves are rising as promising treatment options for high-risk patients with symptomatic mitral valve (MVD) disease unsuitable for alternative treatment options. AIMS: The aim of this study was to examine the clinical, procedural and outcome parameters of patients undergoing SAV or BAV for MVD. METHODS: In this observational and single-center case series, fifteen consecutive patients treated with the Tendyne Mitral Valve System (SAV) and thirty-one patients treated with SAPIEN prosthesis (BAV) were included. RESULTS: The patients (aged 78 years [interquartile range (IQR): 65.5 to 83.1 years], 41% women, EuroSCORE II 10.3% [IQR: 5.5 to 17.0%] were similar regarding baseline characteristics, despite a higher rate of prior heart valve surgery and prevalence of MV stenosis in the SAV-group. At discharge, the SAV-group had a mean transvalvular gradient of 4.2 mmHg, whereas the BAV-group had a mean transvalvular gradient of 6.2 mmHg. None or trace paravalvular leakage (PVL) was assessed in 85% in SAV-group and 80% in the BAV-group. 320 day all-cause and cardiac mortality rates were comparable in both groups (SAV: 26.7% vs BAV: 20%, p = 0.60). Four deaths occurred early in the SAV-group until 32 days of follow-up. CONCLUSIONS: In high-risk patients with MVD, TMVI presents a promising treatment option with encouraging mid-term outcomes and good valve durability. TMVI either with BAV or SAV may be developed to an established treatment option.

Transcatheter Aortic Valve Implantation with ACURATE neo: Results from the PROGRESS PVL Registry.

Objectives: The PROGRESS PVL registry evaluated transcatheter aortic valve implantation (TAVI) in patients treated with ACURATE neo, a supra-annular self-expanding bioprosthetic aortic valve. Background: While clinical outcomes with TAVI are comparable with those achieved with surgery, residual aortic regurgitation (AR) and paravalvular leak (PVL) are common complications. The ACURATE neo valve has a pericardial sealing skirt designed to minimize PVL. Methods: The primary endpoint was the rate of total AR over time, as assessed by a core echocardiographic laboratory. The study enrolled 500 patients (mean age: 81.8 ± 5.1 years; 61% female; mean baseline STS score: 6.0 ± 4.5%) from 22 centers in Europe and Canada; 498 patients were treated with ACURATE neo. Results: The rate of ≥ moderate AR was 4.6% at discharge and 3.1% at 12 months; the rate of ≥ moderate PVL was 4.6% at discharge and 2.6% at 12 months. Paired analyses showed significant improvement in overall PVL between discharge and 12 months (P < 0.001); 64.6% of patients had no change in PVL grade, 24.9% improved, and 10.5% worsened. Patients also exhibited significant improvement in transvalvular gradient (P < 0.001) and effective orifice area (P=0.01). The mortality rate was 2.2% at 30 days and 11.3% at 12 months. The permanent pacemaker implantation (PPI) rate was 10.2% at 30 days and 12.2% at 12 months. Conclusions: Results from PROGRESS PVL support the sustained safety and performance of TAVI with the ACURATE neo valve, showing excellent valve hemodynamics, good clinical outcomes, and significant interindividual improvement in PVL from discharge to 12-month follow-up.

Diagnostic performance of quantitative flow ratio versus fractional flow reserve and resting full-cycle ratio in intermediate coronary lesions.

BACKGROUND: Quantitative flow ratio (QFR) is a novel angiography-derived index aimed to assess the functional relevance of coronary stenoses without pressure wires and adenosine. Good diagnostic yield with the hyperemic fractional flow reserve (FFR) have been reported, while data on the comparison of QFR to non-hyperemic pressure ratios (NHPR) are scarce. METHODS: In this retrospective, observational and single-center study with a large population representative of the real practice, we assessed and compared the diagnostic performance of contrast flow (cQFR) and fixed flow (fQFR) QFR against the NHPR resting full-cyle ratio (RFR) using FFR as reference standard. RESULTS: A total of 626 lesions from 544 patients were investigated. Mean diameter stenosis, FFR, cQFR, fQFR and RFR were 44.8%, 0.842, 0.847, 0.857 and 0.912, respectively. The correlation between cQFR and FFR was stronger (r = 0.830, P < 0.001) compared to that between FFR and RFR (r = 0.777, P < 0.001) and between cQFR and RFR (r = 0.687, P < 0.001). Using FFR ≤0.80 as reference, the sensitivity, specificity, positive predictive value, negative predictive value, and overall diagnostic accuracy for cQFR were 82%, 95%, 87%, 92%, and 91%, respectively. cQFR displayed a higher area under the curve (AUC) than fQFR and RFR (0.938 vs. 0.891 vs. 0.869, P < 0.01). The good diagnostic yield of cQFR appeared to be maintained in different clinical subsets including female gender, aortic valve stenosis and atrial fibrillation, and in different anatomical subsets including focal and non-focal lesions. CONCLUSION: cQFR has a high and better diagnostic performance than the NHPR RFR in predicting FFR-based functional significance of coronary stenoses.

Multiparametric MRI identifies subtle adaptations for demarcation of disease transition in murine aortic valve stenosis.

Aortic valve stenosis (AS) is the most frequent valve disease with relevant prognostic impact. Experimental model systems for AS are scarce and comprehensive imaging techniques to simultaneously quantify function and morphology in disease progression are lacking. Therefore, we refined an acute murine AS model to closely mimic human disease characteristics and developed a high-resolution magnetic resonance imaging (MRI) approach for simultaneous in-depth analysis of valvular, myocardial as well as aortic morphology/pathophysiology to identify early changes in tissue texture and critical transition points in the adaptive process to AS. AS was induced by wire injury of the aortic valve. Four weeks after surgery, cine loops, velocity, and relaxometry maps were acquired at 9.4 T to monitor structural/functional alterations in valve, aorta, and left ventricle (LV). In vivo MRI data were subsequently validated by histology and compared to echocardiography. AS mice exhibited impaired valve opening accompanied by significant valve thickening due to fibrotic remodelling. While control mice showed bell-shaped flow profiles, AS resulted not only in higher peak flow velocities, but also in fragmented turbulent flow patterns associated with enhanced circumferential strain and an increase in wall thickness of the aortic root. AS mice presented with a mild hypertrophy but unaffected global LV function. Cardiac MR relaxometry revealed reduced values for both T1 and T2 in AS reflecting subtle myocardial tissue remodelling with early alterations in mitochondrial function in response to the enhanced afterload. Concomitantly, incipient impairments of coronary flow reserve and myocardial tissue integrity get apparent accompanied by early troponin release. With this, we identified a premature transition point with still compensated cardiac function but beginning textural changes. This will allow interventional studies to explore early disease pathophysiology and novel therapeutic targets.

Characteristics and outcomes of patients screened for transcatheter mitral valve implantation: 1-year results from the CHOICE-MI registry.

AIMS: Transcatheter mitral valve implantation (TMVI) represents a novel treatment option for patients with mitral regurgitation (MR) unsuitable for established therapies. The CHOICE-MI registry aimed to investigate outcomes of patients undergoing screening for TMVI. METHODS AND RESULTS: From May 2014 to March 2021, patients with MR considered suboptimal candidates for transcatheter edge-to-edge repair (TEER) and at high risk for mitral valve surgery underwent TMVI screening at 26 centres. Characteristics and outcomes were investigated for patients undergoing TMVI and for TMVI-ineligible patients referred to bailout-TEER, high-risk surgery or medical therapy (MT). The primary composite endpoint was all-cause mortality or heart failure hospitalization after 1 year. Among 746 patients included (78.5 years, interquartile range [IQR] 72.0-83.0, EuroSCORE II 4.7% [IQR 2.7-9.7]), 229 patients (30.7%) underwent TMVI with 10 different dedicated devices. At 1 year, residual MR ≤1+ was present in 95.2% and the primary endpoint occurred in 39.2% of patients treated with TMVI. In TMVI-ineligible patients (n = 517, 69.3%), rates of residual MR ≤1+ were 37.2%, 100.0% and 2.4% after bailout-TEER, high-risk surgery and MT, respectively. The primary endpoint at 1 year occurred in 28.8% of patients referred to bailout-TEER, in 42.9% of patients undergoing high-risk surgery and in 47.9% of patients remaining on MT. CONCLUSION: This registry included the largest number of patients treated with TMVI to date. TMVI with 10 dedicated devices resulted in predictable MR elimination and sustained functional improvement at 1 year. In TMVI-ineligible patients, bailout-TEER and high-risk surgery represented reasonable alternatives, while MT was associated with poor clinical and functional outcomes.

Transapical mitral valve implantation for treatment of symptomatic mitral valve disease: a real-world multicentre experience.

AIMS: Transcatheter mitral valve implantation (TMVI) is a new treatment option for patients with symptomatic mitral valve (MV) disease. Real-world data have not yet been reported. This study aimed to assess procedural and 30-day outcomes of TMVI in a real-world patient cohort. METHOD AND RESULTS: All consecutive patients undergoing implantation of a transapically delivered self-expanding valve at 26 European centres from January 2020 to April 2021 were included in this retrospective observational registry. Among 108 surgical high-risk patients included (43% female, mean age 75 ± 7 years, mean STS-PROM 7.2 ± 5.3%), 25% was treated for an off-label indication (e.g. previous MV intervention or surgery, mitral stenosis, mitral annular calcification). Patients were highly symptomatic (New York Heart Association [NYHA] functional class III/IV in 86%) and mitral regurgitation (MR) was graded 3+/4+ in 95% (38% primary, 37% secondary, and 25% mixed aetiology). Technical success rate was 96%, and MR reduction to ≤1+ was achieved in all patients with successful implantation. There were two procedural deaths and 30-day all-cause mortality was 12%. At early clinical follow-up, MR reduction was sustained and there were significant reductions of pulmonary pressure (systolic pulmonary artery pressure 52 vs. 42 mmHg, p < 0.001), and tricuspid regurgitation severity (p = 0.013). Heart failure symptoms improved significantly (73% in NYHA class I/II, p < 0.001). Procedural success rate according to MVARC criteria was 80% and was not different in patients treated for an off-label indication (74% vs. 81% for off- vs. on-label, p = 0.41). CONCLUSION: In a real-world patient population, TMVI has a high technical and procedural success rate with efficient and durable MR reduction and symptomatic improvement.

Clinical outcomes of transcatheter aortic valve implantation in patients younger than 70 years rejected for surgery: the AMTRAC registry.

BACKGROUND: The mean age of transcatheter aortic valve implantation (TAVI) patients is steadily decreasing. AIMS: The aim of the study was to describe the characteristics, the indications for and the outcomes of TAVI in patients <70 years old. METHODS: All patients undergoing TAVI (n=8,626) from the 18 participating centres between January 2007 and June 2020 were stratified by age (70). For patients <70, the indications for TAVI were extracted from Heart Team discussions and the baseline characteristics and mortality were compared between the two groups. RESULTS: Overall, 640 (7.4%) patients were <70 (9.1% during 2018-2020, p<0.001); the mean age was 65.0±2.3 years. The younger patients were more often male, with bicuspid valves or needing valve-in-valve procedures. They had a higher prevalence of lung disease and diabetes. In 80.7% of cases, the Heart Team estimated an increased surgical risk and TAVI was selected, reflected by an STS score >4% in 20.4%. Five-year mortality was similar (29.4 vs 29.8%, HR 0.95, p=0.432) in the <70 and >70 groups. In the <70 group, mortality was higher for those referred for TAVI due to an increased surgical risk compared to those referred for other reasons (31.6 vs 24.5%, HR 1.23, p=0.021). Mortality was similar regardless of the STS stratum in patients judged by the Heart Team to be at increased surgical risk (32.6 vs 30.4%, HR 0.98, p=0.715). CONCLUSIONS: Use of TAVI in patients <70 is becoming more frequent. The main reason for choosing TAVI is due to an increased surgical risk not adequately represented by the STS score. The outcomes for these patients are similar to those for older TAVI patients. Dedicated trials of TAVI/SAVR in younger patients are needed to guide decisions concerning expansion of TAVI indications. ((ClinicalTrials.gov: NCT04031274).

Stamp2 Protects From Maladaptive Structural Remodeling and Systolic Dysfunction in Post-Ischemic Hearts by Attenuating Neutrophil Activation.

The six-transmembrane protein of prostate 2 (Stamp2) acts as an anti-inflammatory protein in macrophages by protecting from overt inflammatory signaling and Stamp2 deficiency accelerates atherosclerosis in mice. Herein, we describe an unexpected role of Stamp2 in polymorphonuclear neutrophils (PMN) and characterize Stamp2's protective effects in myocardial ischemic injury. In a murine model of ischemia and reperfusion (I/R), echocardiography and histological analyses revealed a pronounced impairment of cardiac function in hearts of Stamp2-deficient- (Stamp2-/- ) mice as compared to wild-type (WT) animals. This difference was driven by aggravated cardiac fibrosis, as augmented fibroblast-to-myofibroblast transdifferentiation was observed which was mediated by activation of the redox-sensitive p38 mitogen-activated protein kinase (p38 MAPK). Furthermore, we observed increased production of reactive oxygen species (ROS) in Stamp2-/- hearts after I/R, which is the likely cause for p38 MAPK activation. Although myocardial macrophage numbers were not affected by Stamp2 deficiency after I/R, augmented myocardial infiltration by polymorphonuclear neutrophils (PMN) was observed, which coincided with enhanced myeloperoxidase (MPO) plasma levels. Primary PMN isolated from Stamp2-/- animals exhibited a proinflammatory phenotype characterized by enhanced nuclear factor (NF)-κB activity and MPO secretion. To prove the critical role of PMN for the observed phenotype after I/R, antibody-mediated PMN depletion was performed in Stamp2-/- mice which reduced deterioration of LV function and adverse structural remodeling to WT levels. These data indicate a novel role of Stamp2 as an anti-inflammatory regulator of PMN and fibroblast-to-myofibroblast transdifferentiation in myocardial I/R injury.