Circulating MicroRNA-122-5p Is Associated With a Lack of Improvement in Left Ventricular Function After Transcatheter Aortic Valve Replacement and Regulates Viability of Cardiomyocytes Through Extracellular Vesicles.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) is a well-established treatment option for high- and intermediate-risk patients with severe symptomatic aortic valve stenosis. A majority of patients exhibit improvements in left ventricular ejection fraction (LVEF) after TAVR in response to TAVR-associated afterload reduction. However, a specific role for circulating microRNAs (miRNAs) in the improvement of cardiac function for patients after TAVR has not yet been investigated. Here, we profiled the differential expression of miRNAs in circulating extracellular vesicles (EVs) in patients after TAVR and, in particular, the novel role of circulating miR-122-5p in cardiomyocytes. METHODS: Circulating EV-associated miRNAs were investigated by use of an unbiased Taqman-based human miRNA array. Several EV miRNAs (miR-122-5p, miR-26a, miR-192, miR-483-5p, miR-720, miR-885-5p, and miR-1274) were significantly deregulated in patients with aortic valve stenosis at day 7 after TAVR compared with the preprocedural levels in patients without LVEF improvement. The higher levels of miR-122-5p were negatively correlated with LVEF improvement at both day 7 (r=-0.264 and P=0.015) and 6 months (r=-0.328 and P=0.0018) after TAVR. RESULTS: Using of patient-derived samples and a murine aortic valve stenosis model, we observed that the expression of miR-122-5p correlates negatively with cardiac function, which is associated with LVEF. Mice with graded wire injury-induced aortic valve stenosis demonstrated a higher level of miR-122-5p, which was related to cardiomyocyte dysfunction. Murine ex vivo experiments revealed that miR-122-5p is highly enriched in endothelial cells compared with cardiomyocytes. Coculture experiments, copy-number analysis, and fluorescence microscopy with Cy3-labeled miR-122-5p demonstrated that miR-122-5p can be shuttled through large EVs from endothelial cells into cardiomyocytes. Gain- and loss-of-function experiments suggested that EV-mediated shuttling of miR-122-5p increases the level of miR-122-5p in recipient cardiomyocytes. Mechanistically, mass spectrometry, miRNA pulldown, electrophoretic mobility shift assay, and RNA immunoprecipitation experiments confirmed that miR-122-5p interacts with the RNA-binding protein hnRNPU (heterogeneous nuclear ribonucleoprotein U) in a sequence-specific manner to encapsulate miR-122-5p into large EVs. On shuttling, miR-122-5p reduces the expression of the antiapoptotic gene BCL2 by binding to its 3' untranslated region to inhibit its translation, thereby decreasing the viability of target cardiomyocytes. CONCLUSIONS: Increased levels of circulating proapoptotic EV-incorporated miR-122-5p are associated with reduced LVEF after TAVR. EV shuttling of miR-122-5p regulates the viability and apoptosis of cardiomyocytes in a BCL2-dependent manner.

Incidence, Clinical Characteristics, and Impact of Absent Echocardiographic Signs in Patients With Infective Endocarditis After Transcatheter Aortic Valve Implantation.

BACKGROUND: Echocardiography is the primary imaging modality for diagnosis of infective endocarditis (IE) in prosthetic valve endocarditis (PVE) including IE after transcatheter aortic valve implantation (TAVI). This study aimed to evaluate the characteristics and clinical outcomes of patients with absent compared with evident echocardiographic signs of TAVI-IE. METHODS: Patients with definite TAVI-IE derived from the Infectious Endocarditis after TAVI International Registry were investigated comparing those with absent and evident echocardiographic signs of IE defined as vegetation, abscess, pseudo-aneurysm, intracardiac fistula, or valvular perforation or aneurysm. RESULTS: Among 578 patients, 87 (15.1%) and 491 (84.9%) had absent (IE-neg) and evident (IE-pos) echocardiographic signs of IE, respectively. IE-neg were more often treated via a transfemoral access with a self-expanding device and had higher rates of peri-interventional complications (eg, stroke, major vascular complications) during the TAVI procedure (P < .05 for all). IE-neg had higher rates of IE caused by Staphylococcus aureus (33.7% vs 23.2%; P = .038) and enterococci (37.2% vs 23.8%; P = .009) but lower rates of coagulase-negative staphylococci (4.7% vs 20.0%, P = .001). IE-neg was associated with the same dismal prognosis for in-hospital mortality in a multivariate binary regression analysis (odds ratio: 1.51; 95% confidence interval [CI]: .55-4.12) as well as a for 1-year mortality in Cox regression analysis (hazard ratio: 1.10; 95% CI: .67-1.80). CONCLUSIONS: Even with negative echocardiographic imaging, patients who have undergone TAVI and presenting with positive blood cultures and symptoms of infection are a high-risk patient group having a reasonable suspicion of IE and the need for an early treatment initiation.

Mortality prediction of the frailty syndrome in patients with severe mitral regurgitation.

In this prospective observational study, we investigated the impact of geriatric syndromes and frailty on mortality and evaluated the prognostic value of different frailty, nutritional, and geriatric assessment tools in high-risk patients with severe mitral valve regurgitation (MR) who were evaluated for mitral valve therapies including surgical, interventional, and conservative treatment options. We prospectively assessed multiple parameters including the CONUT Score, the Katz Index of independence in activities of daily living (ADL), the Fried Frailty Phenotype (FFP), and the Essential Frailty Toolset (EFT) Score in 127 patients with severe symptomatic MR requiring surgical/interventional treatment versus conservative monitoring. We compared their predictive value on mortality including multivariate regression analysis to identify the most suitable tool to predict outcomes in these patient groups. The frailty syndrome as assessed with the CONUT Score, Katz Index, EFT Score, and FFP was associated with higher rates of comorbidities, significantly higher risk scores such as logistic EuroSCORE, EuroSCORE II, and STS-PROM, and significantly higher mortality rates. The EFT Score and FFP were independent predictors of one-year all-cause mortality in our study cohort (EFT Score: HR 1.9, 95% CI 1.2 to 3.2; p = 0.01; FFP: HR 1.8, 95% CI 1.1 to 3.1; p = 0.015). Geriatric syndromes and frailty are associated with increased mortality in high-risk patients with symptomatic severe MR. The EFT Score and the FFP were independent predictors of one-year all-cause mortality.

Transcatheter Mitral Valve Replacement After Surgical Repair or Replacement: Comprehensive Midterm Evaluation of Valve-in-Valve and Valve-in-Ring Implantation From the VIVID Registry.

BACKGROUND: Mitral valve-in-valve (ViV) and valve-in-ring (ViR) are alternatives to surgical reoperation in patients with recurrent mitral valve failure after previous surgical valve repair or replacement. Our aim was to perform a large-scale analysis examining midterm outcomes after mitral ViV and ViR. METHODS: Patients undergoing mitral ViV and ViR were enrolled in the Valve-in-Valve International Data Registry. Cases were performed between March 2006 and March 2020. Clinical endpoints are reported according to the Mitral Valve Academic Research Consortium (MVARC) definitions. Significant residual mitral stenosis (MS) was defined as mean gradient ≥10 mm Hg and significant residual mitral regurgitation (MR) as ≥ moderate. RESULTS: A total of 1079 patients (857 ViV, 222 ViR; mean age 73.5±12.5 years; 40.8% male) from 90 centers were included. Median STS-PROM score 8.6%; median clinical follow-up 492 days (interquartile range, 76-996); median echocardiographic follow-up for patients that survived 1 year was 772.5 days (interquartile range, 510-1211.75). Four-year Kaplan-Meier survival rate was 62.5% in ViV versus 49.5% for ViR (P<0.001). Mean gradient across the mitral valve postprocedure was 5.7±2.8 mm Hg (≥5 mm Hg; 61.4% of patients). Significant residual MS occurred in 8.2% of the ViV and 12.0% of the ViR patients (P=0.09). Significant residual MR was more common in ViR patients (16.6% versus 3.1%; P<0.001) and was associated with lower survival at 4 years (35.1% versus 61.6%; P=0.02). The rates of Mitral Valve Academic Research Consortium-defined device success were low for both procedures (39.4% total; 32.0% ViR versus 41.3% ViV; P=0.01), mostly related to having postprocedural mean gradient ≥5 mm Hg. Correlates for residual MS were smaller true internal diameter, younger age, and larger body mass index. The only correlate for residual MR was ViR. Significant residual MS (subhazard ratio, 4.67; 95% CI, 1.74-12.56; P=0.002) and significant residual MR (subhazard ratio, 7.88; 95% CI, 2.88-21.53; P<0.001) were both independently associated with repeat mitral valve replacement. CONCLUSIONS: Significant residual MS and/or MR were not infrequent after mitral ViV and ViR procedures and were both associated with a need for repeat valve replacement. Strategies to improve postprocedural hemodynamics in mitral ViV and ViR should be further explored.

Perivalvular Extension of Infective Endocarditis After Transcatheter Aortic Valve Replacement.

BACKGROUND: Infective endocarditis (IE) following transcatheter aortic valve replacement (TAVR) has been associated with a dismal prognosis. However, scarce data exist on IE perivalvular extension (PEE) in such patients. METHODS: This multicenter study included 579 patients who had the diagnosis of definite IE at a median of 171 (53-421) days following TAVR. PEE was defined as the presence of an intracardiac abscess, pseudoaneurysm, or fistula. RESULTS: A total of 105 patients (18.1%) were diagnosed with PEE (perivalvular abscess, pseudoaneurysm, fistula, or a combination in 87, 7, 7, and 4 patients, respectively). A history of chronic kidney disease (adjusted odds ratio [ORadj], 2.08; 95% confidence interval [CI]: 1.27-3.41; P = .003) and IE secondary to coagulase-negative staphylococci (ORadj, 2.71; 95% CI: 1.57-4.69; P < .001) were associated with an increased risk of PEE. Surgery was performed at index IE episode in 34 patients (32.4%) with PEE (vs 15.2% in patients without PEE, P < .001). In-hospital and 2-year mortality rates among PEE-IE patients were 36.5% and 69.4%, respectively. Factors independently associated with an increased mortality were the occurrence of other complications (stroke post-TAVR, acute renal failure, septic shock) and the lack of surgery at index IE hospitalization (padj < 0.05 for all). CONCLUSIONS: PEE occurred in about one-fifth of IE post-TAVR patients, with the presence of coagulase-negative staphylococci and chronic kidney disease determining an increased risk. Patients with PEE-IE exhibited high early and late mortality rates, and surgery during IE hospitalization seemed to be associated with better outcomes.

Frailty, malnutrition, and the endocrine system impact outcome in patients undergoing aortic valve replacement.

BACKGROUND: Frailty is a multidimensional syndrome that affects mortality after aortic valve replacement (AVR). Malnutrition is often associated with the development of frailty. However, data regarding the association of frailty with nutritional status and underlying endocrinological dysregulation in patients with severe aortic valve stenosis are limited. OBJECTIVES: We aimed to systematically screen for frailty and malnutrition, to evaluate for underlying endocrinological disorders and inflammation, and to assess the ability of these parameters to predict outcomes after AVR. METHODS: Our study included 373 patients undergoing transcatheter and surgical AVR. Frailty was assessed using the Fried Frailty Phenotype (FFP), Essential Frailty Toolset, Lawton-Brody, and Katz Index. Malnutrition was measured using the Mini Nutritional Assessment (MNA-LF) and Controlling Nutritional Status. Outcomes of interest were 30-day and one-year mortality. RESULTS: The prevalence of frailty ranged from 6.4% to 65.7% and malnutrition from 5.9% to 10.5%, depending on the evaluation tool. Both parameters were associated with higher levels of cortisol and parathormone as well as lower levels of IGF-1, testosterone, DHEAS, and c-reactive protein. Malnutrition was associated with increased 30-day mortality, and both frailty and malnutrition with increased one-year mortality. In a multivariate analysis, malnutrition measured by the MNA-LF (OR: 2.32 [95%CI: 1.19-4.53], p = 0.01) and frailty as assessed by the FFP (OR: 1.42 [95%CI: 1.02-1.96], p = 0.03) were independent predictors of one-year mortality. CONCLUSION: The prevalence of frailty and malnutrition varies significantly depending on the assessment tool. Both syndromes share common endocrinological alterations. Frailty and malnutrition are independent risk factors for mortality after AVR.

A simplified cardiac damage staging predicts the outcome of patients undergoing TAVR-A multicenter analysis.

BACKGROUND: A significant number of patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR) suffer from extra-aortic cardiac damage. Few studies have investigated strategies to quantify cardiac damage and stratify patients accordingly in different risk groups. The aim of this retrospective multicenter study was to provide a user-friendly simplified staging system based on the proposed classification system of Généreux et al. as a tool to evaluate the prognosis of patients undergoing TAVR more easily. Moreover, we analyzed changes in cardiac damage after TAVR. METHODS: We assessed cardiac damage in patients, who underwent TAVR at the Heart Center Bonn or Düsseldorf, using pre- and postprocedural transthoracic echocardiography. Patients were assigned to the staging system proposed by Généreux et al. according to the severity of their baseline cardiac damage. Based on the established system, we created a simplified staging system to facilitate improved applicability. Finally, we compared clinical outcomes between the groups and evaluated changes in cardiac damage after TAVR. RESULTS: A total of 933 TAVR patients were included in the study. We found a significant association between cardiac damage and 1-year all-cause mortality (stage 0: 0% vs. stage 1: 3% vs. stage 2: 6.6%; p < 0.009). In multivariate analysis, cardiac damage was an independent predictor of 1-year all-cause mortality (hazard ratio: 2.0, 95% confidence interval: 1.1-3.8; p = 0.03). CONCLUSIONS: In patients undergoing TAVR, cardiac damage is associated with enhanced mortality. A simplified staging system can help identify patients at high risk for an adverse outcome.

Feasibility and Safety of an 8 F Angioseal® Vascular Closure Device for Closure of Large Bore Impella CP® Access.

PURPOSE: Percutaneous mechanical circulatory support (pMCS) with the Impella® device is routinely used in cardiogenic shock and high risk percutaneous coronary interventions (PCI). However, safety and feasibility to close the large bore access (LBA) post-hoc remain a challenge. MATERIALS AND METHODS: In patients with planned termination of Impella therapy, corresponding LBA closure was attempted using an undersized AngioSeal® device, which was deployed after insertion of a 0.035 in J-wire through the guidewire access port. Cross-over angiographic visualization before and after deployment as well as in-hospital follow up were performed to assess closure success and screening for short-term adverse events. RESULTS: We evaluated 17 patients (68 year old, IQR 58-76, 71% male) in whom 14 F LBA closure after pMCS using the Impella CP® was achieved with an undersized AngioSeal® device. Clinical indication for pMCS was cardiogenic shock in 94% and protected PCI in 6%. Impella CP® devices were withdrawn after a median of 4 days (IQR 3-6 days). Primary hemostasis was achieved in the majority of patients (14/17; 82%) while single cross-over balloon inflation led to hemostasis in the remaining patients. One patient suffered acute ischemia later in the course of the disease, but this was not directly related to the closure device. In this study, no major bleeding or other device-related adverse events were observed. CONCLUSION: The 8 F AngioSeal® vascular closure device has been safely used for removal of the Impella CP® microaxial pump in most cases of predominantly normal weight patients. This technique may be considered feasible for post-hoc LBA closure in the context of pMCS, especially when preclosure options are not suitable or unavailable.

Percutaneous trans-axilla transcatheter aortic valve replacement.

The left axillary artery is an attractive alternative access route for transcatheter aortic valve replacement (TAVR) and may provide better outcomes compared to other alternatives. Nevertheless, there remain concerns about vascular complications, lack of compressibility, and thorax-related complications. Between March 2019 and March 2021, 13 patients underwent transaxillary TAVR for severe aortic stenosis at the University Hospital Bonn. The puncture was performed with a puncture at the distal segment of the axillary artery through the axilla, with additional femoral access for applying a safety wire inside the axillary artery. Device success was defined according to the VARC 2 criteria. The study participants were advanced in age (77 ± 9 years old), and 54% were female, with an intermediate risk for surgery (STS risk score 4.7 ± 2.0%). The average diameter of the distal segment of the axillary artery was 5.8 ± 1.0 mm (i.e., the puncture site) and 7.6 ± 0.9 mm for the proximal axillary artery. Device success was achieved in all patients. 30-day major adverse cardiac and cerebrovascular events were 0%. With complete percutaneous management, stent-graft implantation was performed at the puncture site in 38.5% of patients. Minor bleeding was successfully managed with manual compression. Moreover, no thorax-related complications, hematomas, or nerve injuries were observed. Percutaneous trans-axilla TAVR was found to be feasible and safe. This modified approach may mitigate the risk of bleeding and serious complications in the thorax and be less invasive than surgical alternatives.

Defining the optimal revascularization strategy during protected high-risk procedures with Impella.

Complete revascularization (CR) in patients with multi-vessel disease improves outcomes. The use of percutaneous left-ventricular assist devices, such as the Impella heart pump, is useful to minimize the risk of haemodynamic compromise in complex higher risk and clinically indicated patients. The recently published data from the PROTECT III trial suggest more CR during Impella-protected percutaneous coronary intervention with more extensive lesion preparation and treatment, resulting in the reduced need for repeat revascularization. To achieve CR and improve survival, procedural guidance by intravascular imaging, extensive lesion preparation, debulking with atherectomy devices, advanced chronic total occlusion revascularization techniques, and post-interventional treatment with modern anti-platelet medication are essential.

Optimal bail-out and complication management strategies in protected high-risk percutaneous coronary intervention with the Impella.

Despite the routine use of percutaneous mechanical circulatory support (pMCS) with the Impella heart pump, vascular and bleeding complications may occur during removal with or without pre-closure. To safely close the large-bore access (LBA), post-hoc selection of the appropriate treatment of vascular complications is critical to patient recovery and survival. Femoral artery access is typically utilized for LBA, and percutaneous axillary artery access is a common alternative, especially in the instance of severe peripheral artery disease. Optimization of patient outcomes and efficiency of pMCS can be achieved with adequate arterial access using state-of-the-art techniques. Impella removal techniques with or without pre-closure will be addressed as well as the management of large-bore femoral access complications. In addition, treatment strategies to manage patient deterioration during a protected high-risk percutaneous coronary intervention will be provided.

Left Ventricular Unloading Is Associated With Lower Mortality in Patients With Cardiogenic Shock Treated With Venoarterial Extracorporeal Membrane Oxygenation: Results From an International, Multicenter Cohort Study.

BACKGROUND: Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is increasingly used to treat cardiogenic shock. However, VA-ECMO might hamper myocardial recovery. The Impella unloads the left ventricle. This study aimed to evaluate whether left ventricular unloading in patients with cardiogenic shock treated with VA-ECMO was associated with lower mortality. METHODS: Data from 686 consecutive patients with cardiogenic shock treated with VA-ECMO with or without left ventricular unloading using an Impella at 16 tertiary care centers in 4 countries were collected. The association between left ventricular unloading and 30-day mortality was assessed by Cox regression models in a 1:1 propensity score-matched cohort. RESULTS: Left ventricular unloading was used in 337 of the 686 patients (49%). After matching, 255 patients with left ventricular unloading were compared with 255 patients without left ventricular unloading. In the matched cohort, left ventricular unloading was associated with lower 30-day mortality (hazard ratio, 0.79 [95% CI, 0.63-0.98]; P=0.03) without differences in various subgroups. Complications occurred more frequently in patients with left ventricular unloading: severe bleeding in 98 (38.4%) versus 45 (17.9%), access site-related ischemia in 55 (21.6%) versus 31 (12.3%), abdominal compartment in 23 (9.4%) versus 9 (3.7%), and renal replacement therapy in 148 (58.5%) versus 99 (39.1%). CONCLUSIONS: In this international, multicenter cohort study, left ventricular unloading was associated with lower mortality in patients with cardiogenic shock treated with VA-ECMO, despite higher complication rates. These findings support use of left ventricular unloading in patients with cardiogenic shock treated with VA-ECMO and call for further validation, ideally in a randomized, controlled trial.

Temporal Trends, Characteristics, and Outcomes of Infective Endocarditis After Transcatheter Aortic Valve Replacement.

BACKGROUND: Procedural improvements combined with the contemporary clinical profile of patients undergoing transcatheter aortic valve replacement (TAVR) may have influenced the incidence and outcomes of infective endocarditis (IE) following TAVR. We aimed to determine the temporal trends, characteristics, and outcomes of IE post-TAVR. METHODS: Observational study including 552 patients presenting definite IE post-TAVR. Patients were divided in 2 groups according to the timing of TAVR (historical cohort [HC]: before 2014; contemporary cohort [CC]: after 2014). RESULTS: Overall incidence rates of IE were similar in both cohorts (CC vs HC: 5.45 vs 6.52 per 1000 person-years; P = .12), but the rate of early IE was lower in the CC (2.29‰ vs 4.89‰, P < .001). Enterococci were the most frequent microorganism. Most patients presented complicated IE ( CC: 67.7%; HC: 69.6%; P = .66), but the rate of surgical treatment remained low (CC: 20.7%; HC: 17.3%; P = .32). The CC exhibited lower rates of in-hospital acute kidney injury (35.1% vs 44.6%; P = .036) and in-hospital (26.6% vs 36.4%; P = .016) and 1-year (37.8% vs 53.5%; P < .001) mortality. Higher logistic EuroScore, Staphylococcus aureus etiology, and complications (stroke, heart failure, and acute renal failure) were associated with in-hospital mortality in multivariable analyses (P < .05 for all). CONCLUSIONS: Although overall IE incidence has remained stable, the incidence of early IE has declined in recent years. The microorganism, high rate of complications, and very low rate of surgical treatment remained similar. In-hospital and 1-year mortality rates were high but progressively decreased over time.

QRS duration is a risk indicator of adverse outcomes after MitraClip.

BACKGROUND: While QRS duration is a known marker of left ventricular (LV) function, little is known about its utility for predicting clinical prognosis after transcatheter mitral valve repair (TMVR). We investigated the association between QRS duration and one-year adverse events after TMVR with the MitraClip system. METHODS: From January 2011 through April 2019, we identified consecutive patients who underwent TMVR. Patients who had prior cardiac resynchronization therapy or a ventricular pacing rhythm were excluded. The patients were divided into two groups according to their QRS duration (<120 or ≥ 120 ms). Cox proportional hazard model was applied to determine the association between QRS duration and the composite outcome (all-cause mortality and re-hospitalization due to heart failure) within 1 year. RESULTS: A total of 348 patients were analyzed. Prolonged QRS duration (≥120 ms) was associated with an increased risk of the composite outcome (adjusted-HR 2.35, 95%CI 1.30-4.24, p = .005). There was a linear relationship between prolonged QRS duration and the increased risk of the composite outcomes. The observed association was consistent both in patients with left ventricular ejection fraction ≤35% and those with >35%. Furthermore, a QRS duration ≥120 ms was associated with lower improvement of LVEF at follow-up (adjusted-ß coefficient - 5.31%, 95%CI -8.17 to -2.46, p < .001). CONCLUSIONS: Prolonged QRS duration was associated with an increased risk of mortality and re-hospitalization and less improvement of LVEF following TMVR. QRS duration could be a useful marker to predict adverse outcomes and LV function after TMVR.

Association of heart failure duration with clinical outcomes after transcatheter mitral valve repair for functional mitral regurgitation.

BACKGROUND: Little is known about the association of heart failure (HF) chronicity with clinical outcomes after transcatheter mitral valve repair (TMVR) for functional mitral regurgitation (MR). METHODS: From January 2011 to March 2019, consecutive patients with functional MR who underwent a MitraClip procedure were analyzed. The patients were divided into two groups according to HF duration-those with duration ≤18 months and those with >18 months. The primary outcome measure was a composite of all-cause mortality and re-HF rehospitalization within 1 year after the procedure. These outcomes were also assessed separately. A Cox proportional hazard model was conducted for investigating the association of HF duration with the primary outcome. RESULTS: A total of 208 patients were analyzed. Patients with HF duration >18 months had a higher rate of the primary outcome compared to those with HF duration ≤18 months (38.1 vs. 19.0%, log-rank p = .003). A longer duration of HF was associated with an increased risk of the primary outcomes (adjusted-HR of >18 months, 2.12 95% CI, 1.14-4.19; p = .03; adjusted-HR (hazard ratios) for 1 year increase, 1.05; 95% CI, 1.02-1.09; p = .004). The association of HF duration with the primary outcomes showed a steep rise during the first 2 years of HF duration and progressive increase after 5 years. CONCLUSIONS: A longer HF duration before TMVR was associated with an increased risk of all-cause mortality or HF rehospitalization. HF duration can be used for the risk stratification marker in patients undergoing TMVR for functional MR.

The effect of transcatheter aortic valve implantation approaches on mortality.

OBJECTIVES: We aimed to evaluate the effect of transcatheter aortic valve implantation (TAVI) approaches on mortality and identify effect modifiers and predictors for mortality. BACKGROUND: Alternative access routes to transfemoral (TF) TAVI include the surgical intra-thoracic direct-aortic (DA) and transapical (TA) approach. TA TAVI has been associated with a higher mortality rate. We hypothesized that this is related to effect modifiers, in particular the left ventricular ejection fraction (LVEF). METHODS: This multicentre study derived its data from prospective registries. To adjust for confounders, we used propensity-score based, stabilized inverse probability weighted Cox regression models. RESULTS: In total, 5,910 patients underwent TAVI via TF (N = 4,072), DA (N = 524), and TA (N = 1,314) access. Compared to TF, 30-day mortality was increased among DA (HR 1.87, 95%CI 1.26-2.78, p = .002) and TA (HR 3.34, 95%CI 2.28-4.89, p < .001) cases. Compared to TF, 5-year mortality was increased among TA cases (HR 1.50, 95%CI 1.24-1.83, p < .001). None of the variables showed a significant interaction between the approaches and mortality. An impaired LVEF (≤35%) increased mortality in all approaches. CONCLUSIONS: The surgical intra-thoracic TA and DA TAVI are both associated with a higher 30-day mortality than TF TAVI. TA TAVI is associated with a higher 5-year mortality than TF TAVI. The DA approach may therefore have some advantages over the TA approach when TF access is not feasible.

Percutaneous mechanical circulatory support from the collaborative multicenter Mechanical Unusual Support in TAVI (MUST) Registry.

OBJECTIVES: To evaluate the use and outcomes of percutaneous mechanical circulatory support (pMCS) utilized during transcatheter aortic valve implantation (TAVI) from high-volume centers. METHODS AND RESULTS: Our international multicenter registry including 13 high-volume TAVI centers with 87 patients (76.5 ± 11.8 years, 63.2% men) who underwent TAVI for severe aortic stenosis and required pMCS (75.9% VA-ECMO, 19.5% Impella CP, 4.6% TandemHeart) during the procedure (prior to TAVI 39.1%, emergent rescue 50.6%, following TAVI 10.3%). The procedures were considered high-risk, with 50.6% having severe left ventricular dysfunction, 24.1% biventricular dysfunction, and 32.2% severe pulmonary hypertension. In-hospital and 1-year mortality were 27.5% and 49.4%, respectively. Patients with prophylactic hemodynamic support had lower periprocedural mortality compared to patients with rescue insertion of pMCS (log rank = 0.013) and patients who did not undergo cardiopulmonary resuscitation during the TAVI procedure had better short and long term survival (log rank <0.001 and 0.015, respectively). CONCLUSIONS: Given the overall survival rate and low frequency of pMCS-related complications, our study results support the use of pMCS prophylactically or during the course of TAVI (bailout) in order to improve clinical outcomes in high-risk procedures or in case of acute life-threatening hemodynamic collapse.

Long-term outcomes after transcatheter aortic valve implantation in failed bioprosthetic valves.

AIMS: Due to bioprosthetic valve degeneration, aortic valve-in-valve (ViV) procedures are increasingly performed. There are no data on long-term outcomes after aortic ViV. Our aim was to perform a large-scale assessment of long-term survival and reintervention after aortic ViV. METHODS AND RESULTS: A total of 1006 aortic ViV procedures performed more than 5 years ago [mean age 77.7 ± 9.7 years; 58.8% male; median STS-PROM score 7.3% (4.2-12.0)] were included in the analysis. Patients were treated with Medtronic self-expandable valves (CoreValve/Evolut, Medtronic Inc., Minneapolis, MN, USA) (n = 523, 52.0%), Edwards balloon-expandable valves (EBEV, SAPIEN/SAPIEN XT/SAPIEN 3, Edwards Lifesciences, Irvine, CA, USA) (n = 435, 43.2%), and other devices (n = 48, 4.8%). Survival was lower at 8 years in patients with small-failed bioprostheses [internal diameter (ID) ≤ 20 mm] compared with those with large-failed bioprostheses (ID > 20 mm) (33.2% vs. 40.5%, P = 0.01). Independent correlates for mortality included smaller-failed bioprosthetic valves [hazard ratio (HR) 1.07 (95% confidence interval (CI) 1.02-1.13)], age [HR 1.21 (95% CI 1.01-1.45)], and non-transfemoral access [HR 1.43 (95% CI 1.11-1.84)]. There were 40 reinterventions after ViV. Independent correlates for all-cause reintervention included pre-existing severe prosthesis-patient mismatch [subhazard ratio (SHR) 4.34 (95% CI 1.31-14.39)], device malposition [SHR 3.75 (95% CI 1.36-10.35)], EBEV [SHR 3.34 (95% CI 1.26-8.85)], and age [SHR 0.59 (95% CI 0.44-0.78)]. CONCLUSIONS: The size of the original failed valve may influence long-term mortality, and the type of the transcatheter valve may influence the need for reintervention after aortic ViV.

Impella Support for Acute Myocardial Infarction Complicated by Cardiogenic Shock.

BACKGROUND: Percutaneous mechanical circulatory support devices are increasingly used in acute myocardial infarction complicated by cardiogenic shock (AMI-CS), despite limited evidence for their effectiveness. The aim of this study was to evaluate outcomes associated with use of the Impella device compared with intra-aortic balloon pump (IABP) and medical treatment in patients with AMI-CS. METHODS: Data of patients with AMI-CS treated with the Impella device at European tertiary care hospitals were collected retrospectively. All patients underwent early revascularization and received optimal medical treatment. Using IABP-SHOCK II (Intraaortic Balloon Pump in Cardiogenic Shock II) trial inclusion and exclusion criteria, 372 patients were identified and included in this analysis. These patients were matched to 600 patients from the IABP-SHOCK II trial. The following baseline criteria were used as matching parameters: age, sex, mechanical ventilation, ejection fraction, prior cardiopulmonary resuscitation, and lactate. Primary end point was 30-day all-cause mortality. RESULTS: In total, 237 patients treated with an Impella could be matched to 237 patients from the IABP-SHOCK II trial. Baseline parameters were similarly distributed after matching. There was no significant difference in 30-day all-cause mortality (48.5% versus 46.4%, P=0.64). Severe or life-threatening bleeding (8.5% versus 3.0%, P<0.01) and peripheral vascular complications (9.8% versus 3.8%, P=0.01) occurred significantly more often in the Impella group. Limiting the analysis to IABP-treated patients as a control group did not change the results. CONCLUSIONS: In this retrospective analysis of patients with AMI-CS, the use of an Impella device was not associated with lower 30-day mortality compared with matched patients from the IABP-SHOCK II trial treated with an IABP or medical therapy. To further evaluate this, a large randomized trial is warranted to determine the effect of the Impella device on outcome in patients with AMI-CS. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT03313687.

Left atrial global function in chronic heart failure patients with functional mitral regurgitation after MitraClip.

BACKGROUND: Left atrial (LA) volumes and function are believed to improve following interventional reduction of mitral regurgitation (MR) with MitraClip. However, exact LA alterations after MitraClip in patients with functional MR and functional mitral regurgitation (FMR) are unknown. OBJECTIVES: We aimed to evaluate the effect of MitraClip on LA volumes and global function in patients with FMR and its importance for patients' prognosis. METHODS: All patients underwent three-dimensionally transthoracic echocardiography with an offline evaluation of LA geometry and strain analysis at baseline and follow-up (FU). FU examinations were planned for 6 and 12 months after MitraClip. RESULTS: We prospectively included 50 consecutive surgical high-risk (logistic EuroSCORE: 17.2 ± 13.9%) patients (77 ± 9 years, 22% female) with symptomatic moderate-to-severe to severe functional MR without atrial fibrillation. Echocardiographic evaluation showed that the E/E' ratio was significantly higher at FU (15.6 ± 7.3, 24.1 ± 13.2, p = .05) without relevant changes in systolic left ventricle (LV) function (p = .5). LA volumes (end-diastolic volume [LA-EDV] and end-systolic volume [LA-ESV]) (LA-EDV: 83.1 ± 39.5 ml, 115.1 ± 55.3 ml, p = .012; LA-ESV: 58.4 ± 33.4 ml, 80.1 ± 43.9 ml, p = .031), muscular mass (105.1 ± 49.3 g, 145.4 ± 70.6 g, p = .013), as well as LA stroke volume (24.6 ± 12.5 ml, 34.9 ± 19.1 ml, p = .016) significantly increased after the procedure. LA ejection fraction (LA-EF: 31.7 ± 12.8%, 31.1 ± 12.3%, p = .8) and atrial global strain (aGS: -10.8 ± 5.4%, -9.7 ± 4.45%, p = .4) showed no significant changes at FU. Despite no relevant changes during FU, the baseline aGS was found to be the strongest predictor for mortality and adverse interventional outcome. CONCLUSION: MitraClip increases atrial stroke volume, atrial volumes, and muscular mass in patients with FMR. We found that the baseline aGS the strongest predictor for mortality, rehospitalization, and higher residual MR at FU.