Microaxial Flow Pump or Standard Care in Infarct-Related Cardiogenic Shock.

BACKGROUND: The effects of temporary mechanical circulatory support with a microaxial flow pump on mortality among patients with ST-segment elevation myocardial infarction (STEMI) complicated by cardiogenic shock remains unclear. METHODS: In an international, multicenter, randomized trial, we assigned patients with STEMI and cardiogenic shock to receive a microaxial flow pump (Impella CP) plus standard care or standard care alone. The primary end point was death from any cause at 180 days. A composite safety end point was severe bleeding, limb ischemia, hemolysis, device failure, or worsening aortic regurgitation. RESULTS: A total of 360 patients underwent randomization, of whom 355 were included in the final analysis (179 in the microaxial-flow-pump group and 176 in the standard-care group). The median age of the patients was 67 years, and 79.2% were men. Death from any cause occurred in 82 of 179 patients (45.8%) in the microaxial-flow-pump group and in 103 of 176 patients (58.5%) in the standard-care group (hazard ratio, 0.74; 95% confidence interval [CI], 0.55 to 0.99; P = 0.04). A composite safety end-point event occurred in 43 patients (24.0%) in the microaxial-flow-pump group and in 11 (6.2%) in the standard-care group (relative risk, 4.74; 95% CI, 2.36 to 9.55). Renal-replacement therapy was administered to 75 patients (41.9%) in the microaxial-flow-pump group and to 47 patients (26.7%) in the standard-care group (relative risk, 1.98; 95% CI, 1.27 to 3.09). CONCLUSIONS: The routine use of a microaxial flow pump with standard care in the treatment of patients with STEMI-related cardiogenic shock led to a lower risk of death from any cause at 180 days than standard care alone. The incidence of a composite of adverse events was higher with the use of the microaxial flow pump. (Funded by the Danish Heart Foundation and Abiomed; DanGer Shock ClinicalTrials.gov number, NCT01633502.).

The adaptor ASC has extracellular and 'prionoid' activities that propagate inflammation.

Microbes or danger signals trigger inflammasome sensors, which induce polymerization of the adaptor ASC and the assembly of ASC specks. ASC specks recruit and activate caspase-1, which induces maturation of the cytokine interleukin 1ß (IL-1ß) and pyroptotic cell death. Here we found that after pyroptosis, ASC specks accumulated in the extracellular space, where they promoted further maturation of IL-1ß. In addition, phagocytosis of ASC specks by macrophages induced lysosomal damage and nucleation of soluble ASC, as well as activation of IL-1ß in recipient cells. ASC specks appeared in bodily fluids from inflamed tissues, and autoantibodies to ASC specks developed in patients and mice with autoimmune pathologies. Together these findings reveal extracellular functions of ASC specks and a previously unknown form of cell-to-cell communication.

High-density lipoprotein mediates anti-inflammatory reprogramming of macrophages via the transcriptional regulator ATF3.

High-density lipoprotein (HDL) mediates reverse cholesterol transport and is known to be protective against atherosclerosis. In addition, HDL has potent anti-inflammatory properties that may be critical for protection against other inflammatory diseases. The molecular mechanisms of how HDL can modulate inflammation, particularly in immune cells such as macrophages, remain poorly understood. Here we identify the transcriptional regulator ATF3, as an HDL-inducible target gene in macrophages that downregulates the expression of Toll-like receptor (TLR)-induced proinflammatory cytokines. The protective effects of HDL against TLR-induced inflammation were fully dependent on ATF3 in vitro and in vivo. Our findings may explain the broad anti-inflammatory and metabolic actions of HDL and provide the basis for predicting the success of new HDL-based therapies.

Aortic Valve Stenosis Causes Accumulation of Extracellular Hemoglobin and Systemic Endothelial Dysfunction.

BACKGROUND: Whether aortic valve stenosis (AS) can adversely affect systemic endothelial function independently of standard modifiable cardiovascular risk factors is unknown. METHODS: We therefore investigated endothelial and cardiac function in an experimental model of AS mice devoid of standard modifiable cardiovascular risk factors and human cohorts with AS scheduled for transcatheter aortic valve replacement. Endothelial function was determined by flow-mediated dilation using ultrasound. Extracellular hemoglobin (eHb) concentrations and NO consumption were determined in blood plasma of mice and humans by ELISA and chemiluminescence. This was complemented by measurements of aortic blood flow using 4-dimensional flow acquisition by magnetic resonance imaging and computational fluid dynamics simulations. The effects of plasma and red blood cell (RBC) suspensions on vascular function were determined in transfer experiments in a murine vasorelaxation bioassay system. RESULTS: In mice, the induction of AS caused systemic endothelial dysfunction. In the presence of normal systolic left ventricular function and mild hypertrophy, the increase in the transvalvular gradient was associated with elevated eryptosis, increased eHb and plasma NO consumption; eHb sequestration by haptoglobin restored endothelial function. Because the aortic valve orifice area in patients with AS decreased, postvalvular mechanical stress in the central ascending aorta increased. This was associated with elevated eHb, circulating RBC-derived microvesicles, eryptotic cells, lower haptoglobin levels without clinically relevant anemia, and consecutive endothelial dysfunction. Transfer experiments demonstrated that reduction of eHb by treatment with haptoglobin or elimination of fluid dynamic stress by transcatheter aortic valve replacement restored endothelial function. In patients with AS and subclinical RBC fragmentation, the remaining circulating RBCs before and after transcatheter aortic valve replacement exhibited intact membrane function, deformability, and resistance to osmotic and hypoxic stress. CONCLUSIONS: AS increases postvalvular swirling blood flow in the central ascending aorta, triggering RBC fragmentation with the accumulation of hemoglobin in the plasma. This increases NO consumption in blood, thereby limiting vascular NO bioavailability. Thus, AS itself promotes systemic endothelial dysfunction independent of other established risk factors. Transcatheter aortic valve replacement is capable of limiting NO scavenging and rescuing endothelial function by realigning postvalvular blood flow to near physiological patterns. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT05603520. URL: https://www.clinicaltrials.gov; Unique identifier: NCT01805739.

Scrutinizing the Role of Venoarterial Extracorporeal Membrane Oxygenation: Has Clinical Practice Outpaced the Evidence?

The use of venoarterial extracorporeal membrane oxygenation (VA-ECMO) for temporary mechanical circulatory support in various clinical scenarios has been increasing consistently, despite the lack of sufficient evidence regarding its benefit and safety from adequately powered randomized controlled trials. Although the ARREST trial (Advanced Reperfusion Strategies for Patients with Out-of-Hospital Cardiac Arrest and Refractory Ventricular Fibrillation) and a secondary analysis of the PRAGUE OHCA trial (Prague Out-of-Hospital Cardiac Arrest) provided some evidence in favor of VA-ECMO in the setting of out-of-hospital cardiac arrest, the INCEPTION trial (Early Initiation of Extracorporeal Life Support in Refractory Out-of-Hospital Cardiac Arrest) has not found a relevant improvement of short-term mortality with extracorporeal cardiopulmonary resuscitation. In addition, the results of the recently published ECLS-SHOCK trial (Extracorporeal Life Support in Cardiogenic Shock) and ECMO-CS trial (Extracorporeal Membrane Oxygenation in the Therapy of Cardiogenic Shock) discourage the routine use of VA-ECMO in patients with infarct-related cardiogenic shock. Ongoing clinical trials (ANCHOR [Assessment of ECMO in Acute Myocardial Infarction Cardiogenic Shock, NCT04184635], REVERSE [Impella CP With VA ECMO for Cardiogenic Shock, NCT03431467], UNLOAD ECMO [Left Ventricular Unloading to Improve Outcome in Cardiogenic Shock Patients on VA-ECMO, NCT05577195], PIONEER [Hemodynamic Support With ECMO and IABP in Elective Complex High-risk PCI, NCT04045873]) may clarify the usefulness of VA-ECMO in specific patient subpopulations and the efficacy of combined mechanical circulatory support strategies. Pending further data to refine patient selection and management recommendations for VA-ECMO, it remains uncertain whether the present usage of this device improves outcomes.

Cytohesins are cytoplasmic ErbB receptor activators.

Signaling by ErbB receptors requires the activation of their cytoplasmic kinase domains, which is initiated by ligand binding to the receptor ectodomains. Cytoplasmic factors contributing to the activation are unknown. Here we identify members of the cytohesin protein family as such factors. Cytohesin inhibition decreased ErbB receptor autophosphorylation and signaling, whereas cytohesin overexpression stimulated receptor activation. Monitoring epidermal growth factor receptor (EGFR) conformation by anisotropy microscopy together with cell-free reconstitution of cytohesin-dependent receptor autophosphorylation indicate that cytohesins facilitate conformational rearrangements in the intracellular domains of dimerized receptors. Consistent with cytohesins playing a prominent role in ErbB receptor signaling, we found that cytohesin overexpression correlated with EGF signaling pathway activation in human lung adenocarcinomas. Chemical inhibition of cytohesins resulted in reduced proliferation of EGFR-dependent lung cancer cells in vitro and in vivo. Our results establish cytohesins as cytoplasmic conformational activators of ErbB receptors that are of pathophysiological relevance.

Percutaneous Transvalvular Microaxial Flow Pump Support in Cardiology.

The Impella device (Impella, Abiomed, Danvers, MA) is a percutaneous transvalvular microaxial flow pump that is currently used for (1) cardiogenic shock, (2) left ventricular unloading (combination of venoarterial extracorporeal membrane oxygenation and Impella concept), (3) high-risk percutaneous coronary interventions, (4) ablation of ventricular tachycardia, and (5) treatment of right ventricular failure. Impella-assisted forward blood flow increased mean arterial pressure and cardiac output, peripheral tissue perfusion, and coronary blood flow in observational studies and some randomized trials. However, because of the need for large-bore femoral access (14 F for the commonly used Impella CP device) and anticoagulation, the incidences of bleeding and ischemic complications are as much as 44% and 18%, respectively. Hemolysis is reported in as many as 32% of patients and stroke in as many as 13%. Despite the rapidly growing use of the Impella device, there are still insufficient data on its effect on outcome and complications on the basis of large, adequately powered randomized controlled trials. The only 2 small and also underpowered randomized controlled trials in cardiogenic shock comparing Impella versus intra-aortic balloon pump did not show improved mortality. Several larger randomized controlled trials are currently recruiting patients or are in preparation in cardiogenic shock (DanGer Shock [Danish-German Cardiogenic Shock Trial; NCT01633502]), left ventricular unloading (DTU-STEMI [Door-To-Unload in ST-Segment-Elevation Myocardial Infarction; NCT03947619], UNLOAD ECMO [Left Ventricular Unloading to Improve Outcome in Cardiogenic Shock Patients on VA-ECMO], and REVERSE [A Prospective Randomised Trial of Early LV Venting Using Impella CP for Recovery in Patients With Cardiogenic Shock Managed With VA ECMO; NCT03431467]) and high-risk percutaneous coronary intervention (PROTECT IV [Impella-Supported PCI in High-Risk Patients With Complex Coronary Artery Disease and Reduced Left Ventricular Function; NCT04763200]).

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.

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.

A novel and simple cardiac magnetic resonance score (PE2RT) predicts outcome in takotsubo syndrome.

OBJECTIVES: To find simple imaging-based features on cardiac magnetic resonance (CMR) that are associated with major adverse cardiovascular events (MACE) in takotsubo syndrome (TTS). METHODS: Patients with TTS referred for CMR between 2007 and 2021 were retrospectively evaluated. Besides standard CMR analysis, commonly known complications of TTS based on expert knowledge were assessed and summarised via a newly developed PE2RT score (one point each for pleural effusion, pericardial effusion, right ventricular involvement, and ventricular thrombus). Clinical follow-up data was reviewed up to three years after discharge. The relationship between PE2RT features and the occurrence of MACE (cardiovascular death or new hospitalisation due to acute myocardial injury, arrhythmia, or chronic heart failure) was examined using Cox regression analysis and Kaplan-Meier estimator. RESULTS: Seventy-nine patients (mean age, 68 ± 14 years; 72 women) with TTS were included. CMR was performed in a median of 4 days (IQR, 2-6) after symptom onset. Over a median follow-up of 13.3 months (IQR, 0.4-36.0), MACE occurred in 14/79 (18%) patients: re-hospitalisation due to acute symptoms (9/79, 11%) or chronic heart failure symptoms (4/79, 5%), and cardiac death (1/79, 1%). Patients with MACE had a higher PE2RT score (median [IQR], 2 [2-3] vs 1 [0-1]; p < 0.001). PE2RT score was associated with MACE on Cox regression analysis (hazard ratio per PE2RT feature, 2.44; 95%CI: 1.62-3.68; p < 0.001). Two or more PE2RT complications were strongly associated with the occurrence of MACE (log-rank p < 0.001). CONCLUSIONS: The introduced PE2RT complication score might enable an easy-to-assess outcome evaluation of TTS patients by CMR. KEY POINTS: • Complications like pericardial effusion, pleural effusion, right ventricular involvement, and ventricular thrombus (summarised as PE2RT features) are relatively common in takotsubo syndrome. • The proposed PE2RT score (one point per complication) was associated with the occurrence of major adverse cardiac events on follow-up. • Complications easily detected by cardiac magnetic resonance imaging can help clinicians derive long-term prognostic information on patients with takotsubo syndrome.

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.

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.

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.

Cardiac MRI in Patients with Prolonged Cardiorespiratory Symptoms after Mild to Moderate COVID-19.

Background Myocardial injury and inflammation at cardiac MRI in patients with COVID-19 have been described in recent publications. Concurrently, a chronic COVID-19 syndrome (CCS) after SARS-CoV-2 infection has been observed and manifests with symptoms such as fatigue and exertional dyspnea. Purpose To explore the relationship between CCS and myocardial injury and inflammation as an underlying cause of the persistent complaints in previously healthy individuals. Materials and Methods In this prospective study from January 2021 to April 2021, study participants without known cardiac or pulmonary diseases prior to SARS-CoV-2 infection who had persistent CCS symptoms such as fatigue or exertional dyspnea after convalescence and healthy control participants underwent cardiac MRI. The cardiac MRI protocol included evaluating the T1 and T2 relaxation times, extracellular volume, T2 signal intensity ratio, and late gadolinium enhancement (LGE). Student t tests, Mann-Whitney U tests, and χ2 tests were used for statistical analysis. Results Forty-one participants with CCS (mean age, 39 years ± 13 [standard deviation]; 18 men) and 42 control participants (mean age, 39 years ± 16; 26 men) were evaluated. The median time between the initial incidence of mild to moderate COVID-19 not requiring hospitalization and undergoing cardiac MRI was 103 days (interquartile range, 88-158 days). Troponin T levels were normal. Parameters indicating myocardial inflammation and edema were comparable between participants with CCS and control participants (T1 relaxation times: 978 msec ± 23 vs 971 msec ± 25 [P = .17]; T2 relaxation times: 53 msec ± 2 vs 52 msec ± 2 [P = .47]; T2 signal intensity ratios: 1.6 ± 0.2 vs 1.6 ± 0.3 [P = .10]). Visible myocardial edema was present in none of the participants. Three of 41 (7%) participants with CCS demonstrated nonischemic LGE, whereas no participants in the control group demonstrated nonischemic LGE (0 of 42 [0%]; P = .07). None of the participants fulfilled the 2018 Lake Louise criteria for the diagnosis of myocarditis. Conclusion Individuals with chronic COVID-19 syndrome who did not undergo hospitalization for COVID-19 did not demonstrate signs of active myocardial injury or inflammation at cardiac MRI. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Lima and Bluemke in this issue.

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.

Aortic Valve Stenosis: From Basic Mechanisms to Novel Therapeutic Targets.

Aortic valve stenosis is the most prevalent heart valve disease worldwide. Although interventional treatment options have rapidly improved in recent years, symptomatic aortic valve stenosis is still associated with high morbidity and mortality. Calcific aortic valve stenosis is characterized by a progressive fibro-calcific remodeling and thickening of the aortic valve cusps, which subsequently leads to valve obstruction. The underlying pathophysiology is complex and involves endothelial dysfunction, immune cell infiltration, myofibroblastic and osteoblastic differentiation, and, subsequently, calcification. To date, no pharmacotherapy has been established to prevent aortic valve calcification. However, novel promising therapeutic targets have been recently identified. This review summarizes the current knowledge of pathomechanisms involved in aortic valve calcification and points out novel treatment strategies.