Advanced CT measures of coronary artery disease with intermediate stenosis in patients with severe aortic valve stenosis.

BACKGROUND: Coronary artery disease (CAD) and severe aortic valve stenosis (AS) frequently coexist. While pre-transcatheter aortic valve replacement (TAVR) computed tomography angiography (CTA) allows to rule out obstructive CAD, interpreting hemodynamic significance of intermediate stenoses is challenging. This study investigates the incremental value of CT-derived fractional flow reserve (CT-FFR), quantitative coronary plaque characteristics (e.g., stenosis degree, plaque volume, and composition), and peri-coronary adipose tissue (PCAT) density to detect hemodynamically significant lesions among those with AS and CAD. MATERIALS AND METHODS: We included patients with severe AS and intermediate coronary lesions (20-80% diameter stenosis) who underwent pre-TAVR CTA and invasive coronary angiogram (ICA) with resting full-cycle ratio (RFR) assessment between 08/16 and 04/22. CTA image analysis included assessment of CT-FFR, quantitative coronary plaque analysis, and PCAT density. Coronary lesions with RFR ≤ 0.89 indicated hemodynamic significance as reference standard. RESULTS: Overall, 87 patients (age 77.9 ± 7.4 years, 38% female) with 95 intermediate coronary artery lesions were included. CT-FFR showed good discriminatory capacity (area under receiver operator curve (AUC) = 0.89, 95% confidence interval (CI) 0.81-0.96, p < 0.001) to identify hemodynamically significant lesions, superior to anatomical assessment, plaque morphology, and PCAT density. Plaque composition and PCAT density did not differ between lesions with and without hemodynamic significance. Univariable and multivariable analyses revealed CT-FFR as the only predictor for functionally significant lesions (odds ratio 1.28 (95% CI 1.17-1.43), p < 0.001). Overall, CT-FFR ≤ 0.80 showed diagnostic accuracy, sensitivity, and specificity of 88.4% (95%CI 80.2-94.1), 78.5% (95%CI 63.2-89.7), and 96.2% (95%CI 87.0-99.5), respectively. CONCLUSION: CT-FFR was superior to CT anatomical, plaque morphology, and PCAT assessment to detect functionally significant stenoses in patients with severe AS. CLINICAL RELEVANCE STATEMENT: CT-derived fractional flow reserve in patients with severe aortic valve stenosis may be a useful tool for non-invasive hemodynamic assessment of intermediate coronary lesions, while CT anatomical, plaque morphology, and peri-coronary adipose tissue assessment have no incremental or additional benefit. These findings might help to reduce pre-transcatheter aortic valve replacement invasive coronary angiogram. KEY POINTS: • Interpreting the hemodynamic significance of intermediate coronary stenoses is challenging in pre-transcatheter aortic valve replacement CT. • CT-derived fractional flow reserve (CT-FFR) has a good discriminatory capacity in the identification of hemodynamically significant coronary lesions. • CT-derived anatomical, plaque morphology, and peri-coronary adipose tissue assessment did not improve the diagnostic capability of CT-FFR in the hemodynamic assessment of intermediate coronary stenoses.

Improving the effectiveness of CPR during interventional procedures.

INTRODUCTION: The number of interventional procedures, such as transcatheter aortic valve replacements or thoracic endovascular aortic repairs, is on the rise. Intraprocedural cardiac arrest is a rare occurrence during high-risk procedures. Modern hybrid-operating tables may adversely affect chest compression quality due to their flexibility. To investigate this relationship, we analyzed the blood pressure generated during chest compressions at different degrees of table extension and assessed the effect of an additional stabilization bar to secure the table. METHODS: A CPR manikin was connected to online blood pressure monitoring on a hybrid operating table. Chest compressions were administered using a mechanical device (at 100 bpm and 80 bpm). Hemodynamic effects were evaluated at various degrees of table extension (0%, 50%, 100% table extension) and with the addition of a stabilization bar. RESULTS: A greater degree of table extension was associated with lower diastolic blood pressure. The addition of a stabilization bar alleviated this drop in diastolic blood pressure and enabled the generation of higher mean arterial pressures at 50% and 100% table extension during chest compressions. CONCLUSION: The flexibility of a hybrid operating table adversely impacts the hemodynamic effect of chest compressions. This effect may be mitigated by using a stabilization bar. These results may be relevant for providing further recommendations for CPR guidelines in hybrid OR settings.

Transcaval Transcatheter Aortic Valve Replacement for Pure Aortic Regurgitation Using a Dedicated Self-Expanding Device.

Novel dedicated devices allow transcatheter treatment of pure aortic regurgitation (AR). The JenaValve Trilogy Heart Valve System was introduced as the first dedicated and on-label AR transcatheter aortic valve replacement system, implementing a locator-based and calcium-independent anchoring mechanism. Here, we present the first-in-human transcatheter aortic valve replacement for pure AR via a transcaval access in a patient with prohibitive alternative arterial accesses.

Low Left-Ventricular Ejection Fraction as a Predictor of Intraprocedural Cardiopulmonary Resuscitation in Patients Undergoing Transcatheter Aortic Valve Implantation.

Transcatheter aortic valve replacement (TAVR) has become an established alternative to surgical aortic valve replacement (AVR) for patients with moderate-to-high perioperative risk. Periprocedural TAVR complications decrease with growing expertise of implanters. Nevertheless, TAVR can still be accompanied by life-threatening adverse events such as intraprocedural cardiopulmonary resuscitation (CPR). This study analyzed the role of a reduced left-ventricular ejection fraction (LVEF) in intraprocedural complications during TAVR. Perioperative and postoperative outcomes from patients undergoing TAVR in a high-volume center (600 cases per year) were analyzed retrospectively with regard to their left-ventricular ejection fraction. Patients with a reduced left-ventricular ejection fraction (EF ≤ 40%) faced a significantly higher risk of perioperative adverse events. Within this cohort, patients were significantly more often in need of mechanical ventilation (35% vs. 19%). These patients also underwent CPR (17% vs. 5.8%), defibrillation due to ventricular fibrillation (13% vs. 5.4%), and heart-lung circulatory support (6.1% vs. 2.5%) more often. However, these intraprocedural adverse events showed no significant impact on postoperative outcomes regarding in-hospital mortality, stroke, or in-hospital stay. A reduced preprocedural LVEF is a risk factor for intraprocedural adverse events. With respect to this finding, the identified patient cohort should be treated with more caution to prevent intraprocedural incidents.

Non-femoral focused transaxillary access in TAVI: GARY data analysis and future trends.

BACKGROUND: In patients not suitable for transfemoral transcatheter aortic valve implantation (TAVI), several access strategies can be chosen. AIM: To evaluate the use and patient outcomes of transaxillary (TAx), transapical (TA), and transaortic (TAo) as alternative access for TAVI in Germany; to further evaluate surgical cutdown vs. percutaneous TAx access. METHODS: All patients entered the German Aortic Valve Registry (GARY) between 2011 and 2019 who underwent non-transfemoral TAVI were included in this analysis. Patients with TA, TAo, or TAx TAVI were compared using a weighted propensity score model. Furthermore, a subgroup analysis was performed for TAx regarding the percutaneous or surgical cutdown approach. RESULTS: Overall, 9686 patients received a non-transfemoral access. A total of 8918 patients (92.1%) underwent TA, 398 (4.1%) TAo, and 370 (3.8%) TAx approaches. Within the TAx subgroup, 141 patients (38.1%) received subclavian cutdown, while 200 (54.1%) underwent a percutaneous approach. The TA patients had a significantly lower 30-day survival than TAx patients (TA 90.92% vs. TAx 95.59%, p = 0.006; TAo 92.22% vs. TAx 95.59%, p = 0.102). Comparing percutaneous and cutdown TAx approaches, no significant differences were seen. However, more vascular complications occurred (TA 1.8%, TAo 2.4%, TAx 12.2%; p < .001), and the hospital length of stay was shorter (TA 12.9 days, TAo 14.1 days, TAx 12 days; p < .001) after TAx access. CONCLUSION: It may be reasonable to consider TAx access first in patients not suitable for TF-TAVI, because the 30-day survival was higher compared with TA access and the 1-year survival was higher compared with TAo access. It remains important for the heart teams to offer alternative access modalities for patients not amenable to the standard TF-TAVI approaches.

Right ventricular dysfunction and impaired right ventricular-pulmonary arterial coupling in paradoxical low-flow, low-gradient aortic stenosis.

AIMS: Paradoxical low-flow, low-gradient aortic stenosis (pLFLG AS) may represent a diagnostic challenge, and its pathophysiology is complex. While left ventricular (LV) systolic function is preserved, right ventricular dysfunction (RVD) and consecutive LV underfilling may contribute to low-flow and reduced stroke volume index, and to adverse outcomes following transcatheter aortic valve implantation (TAVI). The aim of this study was to evaluate the potential role of RVD in pLFLG AS, and to assess the impact of pre-procedural RVD on clinical outcomes after TAVI in patients with pLFLG AS. METHODS AND RESULTS: Out of 2739 native AS patients, who received TAVI at the University of Cologne Heart Center between March 2013 and June 2021, 114 patients displayed pLFLG AS and were included in this study. Right ventricular (RV) function was assessed by transthoracic echocardiography, and a fractional area change (FAC) ≤35% and/or a tricuspid annular plane systolic excursion (TAPSE) <18 mm determined RVD. In addition, the TAPSE/systolic pulmonary artery pressure ratio (TAPSE/sPAP) was monitored as a measure of RV-pulmonary arterial (PA) coupling. An impaired FAC and TAPSE was present in 21.9% and 45.6% of patients, respectively, identifying RVD in 50.0%. RVD (p = 0.016), reduced FAC (p = 0.049), reduced TAPSE (p = 0.035) and impaired RV-PA coupling (TAPSE/sPAP ratio <0.31 mm/mmHg; p = 0.009) were associated with significantly higher all-cause mortality compared to patients with normal RV function. After adjustment for sex, age, body mass index, EuroSCORE II, previous myocardial infarction and mitral regurgitation, independent predictors for all-cause mortality were FAC, sPAP, TAPSE/sPAP ratio, right atrial area, RV diameter and tricuspid regurgitation. CONCLUSIONS: Adverse RV remodelling, RVD and impaired RV-PA coupling provide an explanation for low-flow and reduced stroke volume index in a subset of patients with pLFLG AS, and are associated with excess mortality after TAVI.

Remodeling of the endothelial cell transcriptional program via paracrine and DNA-binding activities of MPO.

Myeloperoxidase (MPO) is an enzyme that functions in host defense. MPO is released into the vascular lumen by neutrophils during inflammation and may adhere and subsequently penetrate endothelial cells (ECs) coating vascular walls. We show that MPO enters the nucleus of ECs and binds chromatin independently of its enzymatic activity. MPO drives chromatin decondensation at its binding sites and enhances condensation at neighboring regions. It binds loci relevant for endothelial-to-mesenchymal transition (EndMT) and affects the migratory potential of ECs. Finally, MPO interacts with the RNA-binding factor ILF3 thereby affecting its relative abundance between cytoplasm and nucleus. This interaction leads to change in stability of ILF3-bound transcripts. MPO-knockout mice exhibit reduced number of ECs at scar sites following myocardial infarction, indicating reduced neovascularization. In summary, we describe a non-enzymatic role for MPO in coordinating EndMT and controlling the fate of endothelial cells through direct chromatin binding and association with co-factors.

Myeloperoxidase induces monocyte migration and activation after acute myocardial infarction.

Introduction: Myocardial infarction (MI) is a significant contributor to morbidity and mortality worldwide. Many individuals who survive the acute event continue to experience heart failure (HF), with inflammatory and healing processes post-MI playing a pivotal role. Polymorphonuclear neutrophils (PMN) and monocytes infiltrate the infarcted area, where PMN release high amounts of the heme enzyme myeloperoxidase (MPO). MPO has numerous inflammatory properties and MPO plasma levels are correlated with prognosis and severity of MI. While studies have focused on MPO inhibition and controlling PMN infiltration into the infarcted tissue, less is known on MPO's role in monocyte function. Methods and results: Here, we combined human data with mouse and cell studies to examine the role of MPO on monocyte activation and migration. We revealed a correlation between plasma MPO levels and monocyte activation in a patient study. Using a mouse model of MI, we demonstrated that MPO deficiency led to an increase in splenic monocytes and a decrease in cardiac monocytes compared to wildtype mice (WT). In vitro studies further showed that MPO induces monocyte migration, with upregulation of the chemokine receptor CCR2 and upregulation of inflammatory pathways identified as underlying mechanisms. Conclusion: Taken together, we identify MPO as a pro-inflammatory mediator of splenic monocyte recruitment and activation post-MI and provide mechanistic insight for novel therapeutic strategies after ischemic injury.

Performance of Purpose-Built vs Off-Label Transcatheter Devices for Aortic Regurgitation: The PURPOSE Study.

BACKGROUND: 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. OBJECTIVES: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Outcomes and predictors of left ventricle recovery in patients with severe left ventricular dysfunction undergoing transcatheter aortic valve implantation.

BACKGROUND: Data on the likelihood of left ventricle (LV) recovery in patients with severe LV dysfunction and severe aortic stenosis undergoing transcatheter aortic valve implantation (TAVI) and its prognostic value are limited. AIMS: We aimed to assess the likelihood of LV recovery following TAVI, examine its association with midterm mortality, and identify independent predictors of LV function. METHODS: In our multicentre registry of 17 TAVI centres in Western Europe and Israel, patients were stratified by baseline LV function (ejection fraction [EF] >/≤30%) and LV response: no LV recovery, LV recovery (EF increase ≥10%), and LV normalisation (EF ≥50% post-TAVI). RESULTS: Our analysis included 10,872 patients; baseline EF was ≤30% in 914 (8.4%) patients and >30% in 9,958 (91.6%) patients. The LV recovered in 544 (59.5%) patients, including 244 (26.7%) patients whose LV function normalised completely (EF >50%). Three-year mortality for patients without severe LV dysfunction at baseline was 29.4%. Compared to this, no LV recovery was associated with a significant increase in mortality (adjusted hazard ratio 1.32; p<0.001). Patients with similar LV function post-TAVI had similar rates of 3-year mortality, regardless of their baseline LV function. Three variables were associated with a higher likelihood of LV recovery following TAVI: no previous myocardial infarction (MI), estimated glomerular filtration rate >60 mL/min, and mean aortic valve gradient (mAVG) (expressed either as a continuous variable or as a binary variable using the standard low-flow, low-gradient aortic stenosis [AS] definition). CONCLUSIONS: LV recovery following TAVI and the extent of this recovery are major determinants of midterm mortality in patients with severe AS and severe LV dysfunction undergoing TAVI. Patients with no previous MI and those with an mAVG >40 mmHg show the best results following TAVI, which are at least equivalent to those for patients without severe LV dysfunction. (ClinicalTrials.gov: NCT04031274).

Comparison of two self-expanding transcatheter heart valves for degenerated surgical bioprostheses: the AVENGER multicentre registry.

BACKGROUND: There is a lack of comparative data on transcatheter aortic valve implantation (TAVI) in degenerated surgical prostheses (valve-in-valve [ViV]). AIMS: We sought to compare outcomes of using two self-expanding transcatheter heart valve (THV) systems for ViV. METHODS: In this retrospective multicentre registry, we included consecutive patients undergoing transfemoral ViV using either the ACURATE neo/neo2 (ACURATE group) or the Evolut R/PRO/PRO+ (EVOLUT group). The primary outcome measure was technical success according to Valve Academic Research Consortium (VARC)-3. Secondary outcomes were 30-day all-cause mortality, device success (VARC-3), coronary obstruction (CO) requiring intervention, rates of severe prosthesis-patient mismatch (PPM), and aortic regurgitation (AR) ≥moderate. Comparisons were made after 1:1 propensity score matching. RESULTS: The study cohort comprised 835 patients from 20 centres (ACURATE n=251; EVOLUT n=584). In the matched cohort (n=468), technical success (ACURATE 92.7% vs EVOLUT 88.9%; p=0.20) and device success (69.7% vs 73.9%; p=0.36) as well as 30-day mortality (2.8% vs 1.6%; p=0.392) were similar between the two groups. The mean gradients and rates of severe PPM, AR ≥moderate, or CO did not differ between the groups. Technical and device success were higher for the ACURATE platform among patients with a true inner diameter (ID) >19 mm, whereas a true ID ≤19 mm was associated with higher device success - but not technical success - among Evolut recipients. CONCLUSIONS: ViV TAVI using either ACURATE or Evolut THVs showed similar procedural outcomes. However, a true ID >19 mm was associated with higher device success among ACURATE recipients, whereas in patients with a true ID ≤19 mm, device success was higher when using Evolut.