The role of Matrix Metalloproteinase-2 and Galectin-3 as predictive biomarkers for all-cause mortality in patients undergoing transfemoral transcatheter aortic valve implantation.

BACKGROUND: Currently available risk scores fail to accurately predict morbidity and mortality in patients with severe symptomatic aortic stenosis who undergo transcatheter aortic valve implantation (TAVI). In this context, biomarkers like matrix metalloproteinase-2 (MMP-2) and Galectin-3 (Gal-3) may provide additional prognostic information. METHODS: Patients with severe aortic stenosis undergoing consecutive, elective, transfemoral TAVI were included. Baseline demographic data, functional status, echocardiographic findings, clinical outcomes and biomarker levels were collected and analysed. RESULTS: The study cohort consisted of 89 patients (age 80.4 ± 5.1 years, EuroScore II 7.1 ± 5.8%). During a median follow-up period of 526 d, 28 patients (31.4%) died. Among those who died, median baseline MMP-2 (alive: 221.6 [170.4; 263] pg/mL vs. deceased: 272.1 [225; 308.8] pg/mL, p < 0.001) and Gal-3 levels (alive: 19.1 [13.5; 24.6] pg/mL vs. deceased: 25 [17.6; 29.5] pg/mL, p = 0.006) were higher than in survivors. In ROC analysis, MMP-2 reached an acceptable level of discrimination to predict mortality (AUC 0.733, 95% CI [0.62; 0.83], p < 0.001), but the predictive value of Gal-3 was poor (AUC 0.677, 95% CI [0.56; 0.79], p = 0.002). Kaplan-Meier and Cox regression analyses showed that patients with MMP-2 and Gal-3 concentrations above the median at baseline had significantly impaired long-term survival (p = 0.004 and p = 0.02, respectively). CONCLUSIONS: In patients with severe aortic stenosis undergoing transfemoral TAVI, MMP-2 and to a lesser extent Gal-3, seem to have additive value in optimizing risk prediction and streamlining decision-making.

Gradual Reperfusion in Cardioplegia-Induced Cardiac Arrest.

Background and Objectives: The majority of cardiac surgical procedures are performed using cardiopulmonary bypass and cardioplegia-induced cardiac arrest. Cardiac arrest and reperfusion may lead to ischemia-reperfusion injury of the myocardium. The aim of this study was to investigate whether gradual reperfusion with a slow increase in oxygen partial pressure leads to a reduction in reperfusion injury. Materials and Methods: Fifty patients undergoing elective cardiac surgery were included in this prospective randomized study. Patients in the hyperoxemic (control) group received conventional reoxygenation (paO2 250-300 mmHg). Patients in the normoxemic (study) group received gradual reoxygenation (1st-minute venous blood with paO2 30-40 mmHg, 2nd-minute arterial blood with paO2 100-150 mmHg). Periprocedural blood samples were taken serially, and markers of myocardial injury were analyzed. In addition, the influence of gradual reoxygenation on hemodynamics, inflammation, and the overall perioperative course was evaluated. Results: There was a trend toward higher CK levels in the hyperoxemia group without statistical significance; however, CK-MB and troponin T levels did not show any statistical difference between the two groups. Potassium concentrations in the coronary sinus were significantly higher in the hyperoxemia group at 3 and 8 min after opening of the aortic cross-clamp (6.88 ± 0.87 mmol/L vs. 6.30 ± 0.91 mmol/L and 5.87 ± 0.73 mmol/L vs. 5.43 ± 0.42 mmol/L, respectively; p = 0.03 and p = 0.02). All other measurements did not show a statistical difference between the two groups. Conclusions: The use of gradual reperfusion in cardiac surgery with cardiopulmonary bypass and cardiac arrest is safe. However, it does not reduce ischemia-reperfusion injury compared to standard hyperoxemic reperfusion.

Dynamics of cerebral oxygenation during rapid ventricular pacing and its impact on outcome in transfemoral transcatheter aortic valve implantation.

BACKGROUND: Cerebral O2 saturation (ScO2 ) reflects cerebral perfusion and can be measured noninvasively by near-infrared spectroscopy (NIRS). OBJECTIVES: In this pilot study, we describe the dynamics of ScO2 during TAVI in nonventilated patients and its impact on procedural outcome. METHODS AND RESULTS: We measured ScO2 of both frontal lobes continuously by NIRS in 50 consecutive analgo-sedated patients undergoing transfemoral TAVI (female 58%, mean age 80.8 years). Compared to baseline ScO2 dropped significantly during RVP (59.3% vs. 53.9%, p < .01). Five minutes after RVP ScO2 values normalized (post RVP 62.6% vs. 53.9% during RVP, p < .01; pre 61.6% vs. post RVP 62.6%, p = .53). Patients with an intraprocedural pathological ScO2 decline of >20% (n = 13) had higher EuroSCORE II (3.42% vs. 5.7%, p = .020) and experienced more often delirium (24% vs. 62%, p = .015) and stroke (0% vs. 23%, p < .01) after TAVI. Multivariable logistic regression revealed higher age and large ScO2 drops as independent risk factors for delirium. CONCLUSIONS: During RVP ScO2 significantly declined compared to baseline. A ScO2 decline of >20% is associated with a higher incidence of delirium and stroke and a valid cut-off value to screen for these complications. NIRS measurement during TAVI procedure may be an easy to implement diagnostic tool to detect patients at high risks for cerebrovascular complications and delirium.

Predictive value of preprocedural procalcitonin for short- and long-term mortality after transfemoral transcatheter aortic valve implantation.

Current risk scores used for patients undergoing transcatheter aortic valve implantation (TAVI) do not reliably predict adverse events after TAVI. Procalcitonin (PCT) is associated with increased atherosclerotic burden and adverse outcomes in patients with cardiovascular disease. The aim of our study is to assess the predictive value of preprocedural serum PCT levels in comparison with established risk scores in TAVI patients. A total of 243 patients undergoing transfemoral TAVI at our institution were included prospectively in the study and 230 of these patients participated in the follow-up 1 year after TAVI. The primary endpoints were mortality at 30 days and 1 year. Multivariable analysis revealed that preprocedural PCT was the only independent predictor of 30-day mortality (HR 2.84; 95% CI 1.59-5.06; p < 0.001) and 1-year mortality (HR 1.90; 95% CI 1.17-3.11; p = 0.01), whereas high-sensitivity C-reactive protein showed no association with procedural outcomes. The results of ROC analysis showed good predictive power of PCT for both outcomes (AUC 0.75; p = 0.0003 for 30-day mortality and AUC 0.71; p < 0.0001 for 1-year mortality). An optimal cut-off value for PCT of 0.06 ng/ml for short- and long-term mortality was determined with the Youden index. A significantly higher mortality rate was observed in the high-PCT group (≥ 0.06 ng/ml) based on Kaplan-Meier analysis (log rank = 12.1; p = 0.001 at 30 days and log rank = 14.2; p = 0.0002 at 1 year). Patients in the high-PCT group also had a considerably worse clinical pro6file. In conclusion, preprocedural PCT is an independent predictor of 30-day and 1-year mortality after TAVI. In particular, a cut-off value of 0.06 ng/ml discriminates patients at higher risk of mortality within 30 days and 1 year of TAVI.

Randomized (CO)mparison of (TRI)fecta and (P)erimount Magna Ease Supraannular Aortic Xenografts-CO.TRI.P Study.

BACKGROUND: Modern supraannular aortic xenografts offer a special design, thus providing maximized opening area for improved hemodynamics. The aim of this study was a prospectively randomized comparison of the Trifecta and the Perimount Magna Ease valves based on metric annulus sizing. METHODS: A total of 100 patients with aortic stenosis undergoing aortic valve replacement (AVR) with or without concomitant procedures were prospectively included. After decalcification of the annulus, stratified intraoperative randomization was performed. The diameter of the aortic annulus was measured using metric Hegar dilators and randomization was based on this metric annulus diameter. Exercise echocardiography was performed at 10-month follow-up. RESULTS: Mean age was 69 years, with 36% female. Predominant implanted valve sizes were 23 mm (39%) and 25 mm (32%). Unadjusted mean pressure gradient was significantly lower and effective orifice area larger for the Trifecta group (10.8 ± 5 vs. 13.2 ± 4 mm Hg, p = 0.02 and 1.93 ± 0.39 vs. 1.70 ± 0.30 cm2, p = 0.002) at discharge. In patients with small annuli, based on the metric annulus size there were no significant differences in gradients or the orifice area. At exercise echocardiography follow-up, there were no significant hemodynamic differences between both prostheses. CONCLUSIONS: The Trifecta and the Perimount Magna Ease prostheses both show excellent hemodynamic performance after AVR. In patients with larger annuli, the Trifecta valve seems to be even superior to the Magna Ease, which may be advantageous in obese patients.

Balloon aortic valvuloplasty to improve candidacy of patients evaluated for transcatheter aortic valve replacement.

OBJECTIVES: Evaluate the role of balloon aortic valvuloplasty (BAV) in improving candidacy of patients for transcatheter aortic valve replacement (TAVR). BACKGROUND: Patients who are not candidates for TAVR may undergo BAV to improve functional and clinical status. METHODS: 117 inoperable or high-risk patients with critical aortic stenosis underwent BAV as a bridge-to-decision for TAVR. Frailty measures including gait speed, serum albumin, hand grip, activities of daily living (ADL); and NYHA functional class before and after BAV were compared. RESULTS: Mean age was 81.6 ± 8.5 years and the mean Society of Thoracic Surgeons predicted risk of mortality was 9.57 ± 5.51, with 19/117 (16.2%) patients non-ambulatory. There was no significant change in mean GS post-BAV, but all non-ambulatory patients completed GS testing at follow-up. Albumin and hand grip did not change after BAV, but there was a significant improvement in mean ADL score (4.85 ± 1.41 baseline to 5.20 ± 1.17, P = 0.021). The number of patients with Class IV congestive heart failure (CHF) was significantly lower post BAV (71/117 [60.7%] baseline versus 18/117 [15.4%], P = 0.008). 78/117 (66.7%) of patients were referred to definitive valve therapy after BAV. CONCLUSIONS: When evaluating frailty measures post BAV, we saw no significant improvement in mean GS, however, we observed a significant improvement in non-ambulatory patients and ADL scores. We also describe improved Class IV CHF symptoms. With this improved health status, the majority of patients underwent subsequent valve therapy, demonstrating that BAV may improve candidacy of patients for TAVR.

Tricuspid regurgitation diagnosis and treatment.

Tricuspid regurgitation (TR) is the most common lesion of the tricuspid valve (TV). Mild TR is common and usually is benign. However, moderate or severe TR can lead to irreversible myocardial damage and adverse outcomes. Despite these findings, few patients with significant TR undergo surgery. The treatment of functional (secondary) TR in particular remains controversial because of high rates of residual or recurrent TR and poor outcomes following surgical intervention. Traditional teaching that functional TR resolves on its own if the underlying disease is successfully treated has proven to be incorrect. This review aims to clarify management of TR by describing the anatomy, pathophysiology, diagnosis, and treatment of TR, including the eventual possibility of percutaneous TV therapy.

The future of transcatheter aortic valve implantation.

Since the introduction of transcatheter aortic valve implantation (TAVI) into clinical practice, the treatment of aortic stenosis has changed dramatically. In the past, medical therapy with or without balloon aortic valvuloplasty was the only option for inoperable patients. More recently, TAVI has become the treatment of choice for these patients and the preferred alternative for high-risk operable patients. Surgical aortic valve replacement (SAVR) currently remains the gold standard for patients at low or intermediate operative risk. As randomized trials have demonstrated comparable results between TAVI and SAVR in the high-risk population, there is now a clear trend towards performing TAVI even in intermediate-risk patients while awaiting the results of randomized trials in that population. Nevertheless, there are still questions regarding TAVI involving paravalvular leak (PVL), stroke, pacemaker requirements, and durability that remain to be more definitively answered before TAVI can routinely be performed in a broader, lower risk population. Improvements in patient selection, imaging, and second and third generation devices have decreased the incidence of PVLs and vascular complications that followed the earliest TAVI procedures, but the rates of perioperative stroke and permanent pacemaker implantation must still be addressed. Furthermore, the long-term durability of TAVI devices and a role for post-procedure antithrombotic management remain unanswered. Until these questions are more clearly answered, it is the Heart Team's task to determine the optimal treatment for each patient based on risk scores, frailty metrics, comorbidities, patient preference, and potential for improvement in quality of life.

Transcatheter aortic valve implantation--update and evidence.

Transcatheter aortic valve implantation (T-AVI) has become the standard of care for high-risk patients suffering from severe aortic valve stenosis. More than 60,000 implants have been performed to date. While the first-generation T-AVI devices had some specific issues, the advancements in these first-generation devices and the development of second-generation devices significantly reduced the incidence of peri-procedural complications. The two major access routes are the transfemoral (TF) and the transapical (TA) approach. Both approaches have their advantages and should be considered equal alternatives for finding the best treatment option for the individual patient. Currently there are discussions about extending the indication to patients with lower risk profiles. However, there is no real evidence to justify an expansion, as results of surgical aortic valve replacement in low and intermediate risk patients are excellent.

Prognostic utility of mid-regional pro-adrenomedullin and growth differentiation factor 15 in patients undergoing transfemoral transcatheter aortic valve implantation.

BACKGROUND: Risk prediction in patients with severe, symptomatic aortic stenosis (AS) undergoing transcatheter aortic valve implantation (TAVI) remains an unsolved issue. In addition to classical risk scoring systems, novel circulating biomarkers like mid-regional pro-adrenomedullin (MR-proADM) and growth differentiation factor 15 (GDF-15) may be of value in assessing risk. METHODS: Consecutive patients undergoing elective transfemoral TAVI were included in this prospective observational study. Baseline information, imaging findings, blood samples, and clinical outcomes were collected. Blood levels of the classical biomarkers interleukin-6 (IL-6) and high-sensitivity C-reactive peptide (hsCRP) and of the novel biomarkers MR-proADM and GDF-15 were measured and their predictive utility for mortality assessed. RESULTS: The study cohort consisted of 92 patients undergoing TAVI. The median age was 80.7 years [IQR 77.2;83.3], and 48 (52.2%) were male. Analysis of the area under the curve (AUC) of the receiver-operating characteristics showed that the hsCRP levels discriminated poorly (AUC 0.66, 95% CI [0.52;0.8], p = 0.027), whereas all other biomarkers reached a higher level of discrimination (IL-6: AUC 0.76, 95% CI [0.66;0.86], p < 0.001; MR-proADM: AUC 0.73, 95% CI [0.61;0.85], p = 0.002; GDF-15: AUC 0.73, 95% CI [0.61;0.85], p = 0.002). Kaplan-Meier analysis in conjunction with Youden J-statistics yielded the optimal cutoff points for each biomarker to predict survival: IL-6 4.65 pg/mL, hsCRP 12.9 mg/L, MR-proADM 1.02 nmol/L, and GDF-15 2400.1 pg/mL. CONCLUSION: Novel circulating biomarkers like MR-proADM and GDF-15 may provide additional value in predicting survival after TAVI.

Improved integration of single-cell transcriptome data demonstrates common and unique signatures of heart failure in mice and humans.

BACKGROUND: Cardiovascular research heavily relies on mouse (Mus musculus) models to study disease mechanisms and to test novel biomarkers and medications. Yet, applying these results to patients remains a major challenge and often results in noneffective drugs. Therefore, it is an open challenge of translational science to develop models with high similarities and predictive value. This requires a comparison of disease models in mice with diseased tissue derived from humans. RESULTS: To compare the transcriptional signatures at single-cell resolution, we implemented an integration pipeline called OrthoIntegrate, which uniquely assigns orthologs and therewith merges single-cell RNA sequencing (scRNA-seq) RNA of different species. The pipeline has been designed to be as easy to use and is fully integrable in the standard Seurat workflow.We applied OrthoIntegrate on scRNA-seq from cardiac tissue of heart failure patients with reduced ejection fraction (HFrEF) and scRNA-seq from the mice after chronic infarction, which is a commonly used mouse model to mimic HFrEF. We discovered shared and distinct regulatory pathways between human HFrEF patients and the corresponding mouse model. Overall, 54% of genes were commonly regulated, including major changes in cardiomyocyte energy metabolism. However, several regulatory pathways (e.g., angiogenesis) were specifically regulated in humans. CONCLUSIONS: The demonstration of unique pathways occurring in humans indicates limitations on the comparability between mice models and human HFrEF and shows that results from the mice model should be validated carefully. OrthoIntegrate is publicly accessible (https://github.com/MarianoRuzJurado/OrthoIntegrate) and can be used to integrate other large datasets to provide a general comparison of models with patient data.

Outcomes After Early Postoperative Myocardial Infarction Due to Graft Failure in Patients Undergoing Coronary Artery Bypass Grafting.

BACKGROUND: Early graft failure (EGF) after coronary artery bypass grafting (CABG) occurs in up to 12% of grafts, but is often clinically unapparent. EGF may result in perioperative myocardial infarction with consequently increased mortality. The aim of the present study was to analyze the incidence of clinically apparent EGF in patients undergoing CABG and the influence on mortality. METHODS: We analyzed outcomes of consecutive patients undergoing CABG from January 2015 to December 2018 with respect to postoperative emergency coronary angiography (CAG) due to suspected EGF and 30-day mortality. Patients with CAG-documented EGF were matched to patients without EGF to examine predictors of mortality. RESULTS: The analysis included 5638 patients undergoing CABG. Eighty-six patients (1.5%) underwent emergency CAG due to suspected EGF. Clinically apparent EGF was observed in 61 of these patients (70.9%), whereas 14 (16.3%) had a culprit lesion in a native coronary artery. The majority of patients (n = 45; 52.3%) were treated with percutaneous coronary intervention and 31 (36%) underwent re-do CABG. The remaining patients were treated conservatively. The 30-day mortality rate of suspected EGF patients undergoing CAG was 22.4% (n = 19), which was higher than the mortality rate of 2.8% overall (P<.001); this remained higher after matching the EGF patients with the control group (11 [20.4%] vs 2 [4.0%]; P=.02). CONCLUSION: Emergency CAG after CABG is rare and is primarily carried out in patients with EGF. The 30-day mortality rate of these patients is high, and EGF is an independent predictor of mortality. Perioperative CAG with subsequent treatment is mandatory in these patients.

Fibroblast growth factor 23 as a biomarker of right ventricular dysfunction in pulmonary hypertension.

BACKGROUND: Fibroblast growth factor 23 (FGF-23) has been associated with left ventricular hypertrophy (LVH) and heart failure. However, its role in right ventricular (RV) remodeling and RV failure is unknown. This study analyzed the utility of FGF-23 as a biomarker of RV function in patients with pulmonary hypertension (PH). METHODS: In this observational study, FGF-23 was measured in the plasma of patients with PH (n = 627), dilated cardiomyopathy (DCM, n = 59), or LVH with severe aortic stenosis (n = 35). Participants without LV or RV abnormalities served as controls (n = 36). RESULTS: Median FGF-23 plasma levels were higher in PH patients than in healthy controls (p < 0.001). There were no significant differences between PH, DCM, and LVH patients. Analysis across tertiles of FGF-23 levels in PH patients revealed an association between higher FGF-23 levels and higher levels of NT-proBNP and worse renal function. Furthermore, patients in the high-FGF-23 tertile had a higher pulmonary vascular resistance (PVR), mean pulmonary artery pressure, and right atrial pressure and a lower cardiac index (CI) than patients in the low tertile (p < 0.001 for all comparisons). Higher FGF-23 levels were associated with higher RV end-diastolic diameter and lower tricuspid annular plane systolic excursions (TAPSE) and TAPSE/PASP. Receiver operating characteristic analysis revealed FGF-23 as a good predictor of RV maladaptation, defined as TAPSE < 17 mm and CI < 2.5 L/min/m2. Association of FGF-23 with parameters of RV function was independent of the glomerular filtration rate in regression analysis. CONCLUSION: FGF-23 may serve as a biomarker for maladaptive RV remodeling in patients with PH.

Single-nuclear transcriptome profiling identifies persistent fibroblast activation in hypertrophic and failing human hearts of patients with longstanding disease.

AIMS: Cardiac fibrosis drives the progression of heart failure in ischaemic and hypertrophic cardiomyopathy. Therefore, the development of specific anti-fibrotic treatment regimens to counteract cardiac fibrosis is of high clinical relevance. Hence, this study examined the presence of persistent fibroblast activation during longstanding human heart disease at a single-cell resolution to identify putative therapeutic targets to counteract pathological cardiac fibrosis in patients. METHODS AND RESULTS: We used single-nuclei RNA sequencing with human tissues from two samples of one healthy donor, and five hypertrophic and two failing hearts. Unsupervised sub-clustering of 7110 nuclei led to the identification of 7 distinct fibroblast clusters. De-convolution of cardiac fibroblast heterogeneity revealed a distinct population of human cardiac fibroblasts with a molecular signature of persistent fibroblast activation and a transcriptional switch towards a pro-fibrotic extra-cellular matrix composition in patients with established cardiac hypertrophy and heart failure. This sub-cluster was characterized by high expression of POSTN, RUNX1, CILP, and a target gene adipocyte enhancer-binding protein 1 (AEBP1) (all P < 0.001). Strikingly, elevated circulating AEBP1 blood level were also detected in a validation cohort of patients with confirmed cardiac fibrosis and hypertrophic cardiomyopathy by cardiac magnetic resonance imaging (P < 0.01). Since endogenous AEBP1 expression was increased in patients with established cardiac hypertrophy and heart failure, we assessed the functional consequence of siRNA-mediated AEBP1 silencing in human cardiac fibroblasts. Indeed, AEBP1 silencing reduced proliferation, migration, and fibroblast contractile capacity and α-SMA gene expression, which is a hallmark of fibroblast activation (all P < 0.05). Mechanistically, the anti-fibrotic effects of AEBP1 silencing were linked to transforming growth factor-beta pathway modulation. CONCLUSION: Together, this study identifies persistent fibroblast activation in patients with longstanding heart disease, which might be detected by circulating AEBP1 and therapeutically modulated by its targeted silencing in human cardiac fibroblasts.

Presepsin predicts 1-year all-cause mortality better than N-terminal pro-B-type natriuretic peptide in patients undergoing transcatheter aortic valve implantation.

Aim: Presepsin is a sensitive biomarker for the diagnosis and estimation of prognosis in septic patients. The prognostic role of presepsin in patients undergoing transcatheter aortic valve implantation (TAVI) has never been investigated. Patients, materials & methods: In 343 patients, presepsin and N-terminal pro-B-type natriuretic peptide were measured before TAVI. One-year all-cause mortality was used as outcome measure. Results: Patients with high presepsin levels were more likely to succumb than patients with low presepsin values (16.9% vs 12.3%; p = 0.015). Elevated presepsin remained a significant predictor of 1-year all-cause mortality (odds ratio: 2.2 [95% CI: 1.12-4.29]; p = 0.022) after adjustment. N-terminal pro-B-type natriuretic peptide did not predict 1-year all-cause mortality. Conclusion: Elevated baseline presepsin levels are an independent predictor of 1-year mortality in TAVI patients.

Presepsin is a rather novel blood parameter that is most commonly used for the detection of severe infections. However, in patients without infections who are undergoing elective surgery, elevated baseline presepsin levels were also found to be associated with worse survival. In this study, researchers wanted to know whether increased presepsin levels can also predict worse survival in patients who are planned for transcatheter aortic valve implantation. To do so, they looked at the 1-year death rate of these patients and distinguished between low and high presepsin levels determined before the procedure. Patients with elevated presepsin levels before the procedure had a worse outcome after 1 year compared with those with low presepsin levels. Measurement of presepsin before the transcatheter aortic valve implantation procedure could help identify patients who are at a higher long-term risk, and accordingly a closer monitoring of these patients during the follow-up period might be warranted.

A human cell atlas of the pressure-induced hypertrophic heart.

Pathological cardiac hypertrophy is a leading cause of heart failure, but knowledge of the full repertoire of cardiac cells and their gene expression profiles in the human hypertrophic heart is missing. Here, by using large-scale single-nucleus transcriptomics, we present the transcriptional response of human cardiomyocytes to pressure overload caused by aortic valve stenosis and describe major alterations in cardiac cellular crosstalk. Hypertrophied cardiomyocytes had reduced input from endothelial cells and fibroblasts. Genes encoding Eph receptor tyrosine kinases, particularly EPHB1, were significantly downregulated in cardiomyocytes of the hypertrophied heart. Consequently, EPHB1 activation by its ligand ephrin (EFN)B2, which is mainly expressed by endothelial cells, was reduced. EFNB2 inhibited cardiomyocyte hypertrophy in vitro, while silencing its expression in endothelial cells induced hypertrophy in co-cultured cardiomyocytes. Our human cell atlas of the hypertrophied heart highlights the importance of intercellular crosstalk in disease pathogenesis and provides a valuable resource.

Clinical outcomes following transapical TAVR with ACURATE neo in the CHANGE neo TA study.

BACKGROUND: A transapical (TA) approach to transcatheter aortic valve replacement (TAVR) may be used when a transfemoral (TF) approach is not feasible. The CHANGE neo TA study evaluated patients treated in routine clinical practice via TA-TAVR with the ACURATE neo bioprosthetic aortic valve. METHODS AND RESULTS: This single-arm post-market study had a planned enrolment of 200 subjects; enrolment was terminated early due to declining TA-TAVR procedures at participating centers. Final enrolment was 107 patients (mean age: 79.3 years; 54.2% female; mean STS score at baseline: 6.2%). The mortality rate in the intent-to-treat population was 11.2% at 30 days (primary endpoint) and 25.6% at 12 months. The VARC-2 composite endpoint for 30-day safety occurred in 24.3% of patients. Six patients (5.6%) received a permanent pacemaker within 30 days. Site-reported echocardiographic data showed early improvements in mean aortic valve gradient (baseline: 38.8 [SD 13.1] mmHg, discharge: 6.7 [SD 3.7] mmHg) and effective orifice area (baseline: 0.7 [SD 0.2] cm2, discharge: 1.9 [SD 0.6] cm2), and the discharge rate of paravalvular regurgitation was low (74.7% none/trace, 24.2% mild, 1.1% severe). CONCLUSIONS: TA-TAVR with the ACURATE neo valve system yields acceptable clinical outcomes, providing an alternative for patients with aortic stenosis who are not candidates for TF-TAVR.

New developments in transcatheter therapy of mitral valve disease.

Mitral valve regurgitation (MR) belongs to one of the most common acquired valve diseases in western countries with increasing prevalence in older age. For patients with high perioperative risk and older age prohibitive for valve surgery, the development of transcatheter mitral valve therapies offers new options. Assessment of the severity and etiology of MR and thorough imaging of the mitral valve anatomy and pathology are necessary prerequisites for appropriate decision making in the field of transcatheter mitral valve therapies. Different transcatheter repair and replacement techniques are on the market, most of them mimicking surgical techniques. With some techniques (e.g., the MitraClip device), there is good clinical experience (>80,000 devices implanted worldwide), and evidence (three randomized studies), whereas for newer procedures, safety and efficacy data are still very limited. Transcatheter mitral repair and replacement techniques have to be considered as complementary treatment options for high-risk patients indicated by the Heart Teams. The different techniques and devices will be introduced and discussed in the following paper.