ABSTRACT
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.).
Subject(s)
Heart-Assist Devices , ST Elevation Myocardial Infarction , Shock, Cardiogenic , Aged , Female , Humans , Male , Heart-Assist Devices/adverse effects , Incidence , Shock, Cardiogenic/etiology , Shock, Cardiogenic/mortality , Shock, Cardiogenic/surgery , ST Elevation Myocardial Infarction/complications , ST Elevation Myocardial Infarction/mortality , ST Elevation Myocardial Infarction/therapy , Treatment Outcome , Assisted Circulation/adverse effects , Assisted Circulation/instrumentation , Assisted Circulation/methodsABSTRACT
BACKGROUND AND AIMS: There is significant potential to streamline the clinical pathway for patients undergoing transcatheter aortic valve implantation (TAVI). The purpose of this study was to evaluate the effect of implementing BENCHMARK best practices on the efficiency and safety of TAVI in 28 sites in 7 European countries. METHODS: This was a study of patients with severe symptomatic aortic stenosis (AS) undergoing TAVI with balloon-expandable valves before and after implementation of BENCHMARK best practices. Principal objectives were to reduce hospital length of stay (LoS) and duration of intensive care stay. Secondary objective was to document patient safety. RESULTS: Between January 2020 and March 2023, 897 patients were documented prior to and 1491 patients after the implementation of BENCHMARK practices. Patient characteristics were consistent with a known older TAVI population and only minor differences. Mean LoS was reduced from 7.7 ± 7.0 to 5.8 ± 5.6 days (median 6 vs. 4 days; P < .001). Duration of intensive care was reduced from 1.8 to 1.3 days (median 1.1 vs. 0.9 days; P < .001). Adoption of peri-procedure best practices led to increased use of local anaesthesia (96.1% vs. 84.3%; P < .001) and decreased procedure (median 47 vs. 60â min; P < .001) and intervention times (85 vs. 95â min; P < .001). Thirty-day patient safety did not appear to be compromised with no differences in all-cause mortality (0.6% in both groups combined), stroke/transient ischaemic attack (1.4%), life-threatening bleeding (1.3%), stage 2/3 acute kidney injury (0.7%), and valve-related readmission (1.2%). CONCLUSIONS: Broad implementation of BENCHMARK practices contributes to improving efficiency of TAVI pathway reducing LoS and costs without compromising patient safety.
Subject(s)
Aortic Valve Stenosis , Benchmarking , Length of Stay , Transcatheter Aortic Valve Replacement , Humans , Transcatheter Aortic Valve Replacement/methods , Aortic Valve Stenosis/surgery , Male , Female , Aged, 80 and over , Length of Stay/statistics & numerical data , Aged , Critical Pathways , Europe/epidemiology , Postoperative Complications/epidemiology , Postoperative Complications/prevention & control , Patient SafetyABSTRACT
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.
Subject(s)
Aortic Valve Stenosis , Circulating MicroRNA , Extracellular Vesicles , MicroRNAs , Transcatheter Aortic Valve Replacement , Humans , Mice , Animals , Transcatheter Aortic Valve Replacement/methods , Ventricular Function, Left/physiology , Stroke Volume/physiology , Endothelial Cells , Aortic Valve Stenosis/surgery , MicroRNAs/genetics , Proto-Oncogene Proteins c-bcl-2 , Aortic Valve/surgery , Treatment OutcomeABSTRACT
Cardiogenic shock (CS) is a complex clinical syndrome with a high risk of mortality. The recent, rapid development of temporary mechanical circulatory support (tMCS) has altered CS treatment. While catecholamines remain the cornerstone of CS therapy, tMCS usage has increased. According to shock severity, different treatment strategies including catecholamines alone, catecholamines and tMCS, or multiple tMCS might be used. State-of-the-art implantation techniques are necessary to avoid complications linked to the invasive nature of tMCS. In particular, bleeding and access-site complications might counteract the potential haemodynamic benefit of a percutaneous ventricular assist device. In this review, we describe the role of catecholamines in CS treatment and present the different tMCS devices with an explanation on how to use them according to CS aetiology and severity. Finally, an overview of the best practice for device implantation is provided.
ABSTRACT
A growing body of evidence indicates that the benefits of temporary mechanical circulatory support (tMCS) in patients with cardiogenic shock (CS) is dependent on its aetiology and timing of implantation. As such, appropriate diagnosis, screening, selection, and treatment is crucial to achieving good outcomes with tMCS. Here, the latest guidance on CS phenotypes and diagnostics for correctly identifying tMCS candidates is discussed. This includes comprehensive overviews of patient screening with attention given to differences in CS presentation between the sexes, and contraindications for mechanical circulatory support.
ABSTRACT
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.
Subject(s)
Aortic Valve Stenosis , Frailty , Malnutrition , Transcatheter Aortic Valve Replacement , Aged , Aortic Valve/diagnostic imaging , Aortic Valve/surgery , Aortic Valve Stenosis/diagnostic imaging , Aortic Valve Stenosis/surgery , Endocrine System , Frail Elderly , Frailty/diagnosis , Humans , Malnutrition/diagnosis , Risk Factors , Treatment OutcomeABSTRACT
BACKGROUND: Pro-apoptotic and pro-inflammatory ceramides are crucially involved in atherosclerotic plaque development. Local cellular ceramide accumulation mediates endothelial apoptosis, especially in type 2 diabetes mellitus, which is a major cardiovascular risk factor. In recent years, large extracellular vesicles (lEVs) have been identified as an important means of intercellular communication and as regulators of cardiovascular health and disease. A potential role for lEVs as vehicles for ceramide transfer and inductors of diabetes-associated endothelial apoptosis has never been investigated. METHODS AND RESULTS: A mass-spectrometric analysis of human coronary artery endothelial cells (HCAECs) and their lEVs revealed C16 ceramide (d18:1-16:0) to be the most abundant ceramide in lEVs and to be significantly increased in lEVs after hyperglycemic injury to HCAECs. The increased packaging of ceramide into lEVs after hyperglycemic injury was shown to be dependent on neutral sphingomyelinase 2 (nSMase2), which was upregulated in glucose-treated HCAECs. lEVs from hyperglycemic HCAECs induced apoptosis in the recipient HCAECs compared to native lEVs from untreated HCAECs. Similarly, lEVs from hyperglycemic mice after streptozotocin injection induced higher rates of apoptosis in murine endothelial cells compared to lEVs from normoglycemic mice. To generate lEVs with high levels of C16 ceramide, ceramide was applied exogenously and shown to be effectively packaged into the lEVs, which then induced apoptosis in lEV-recipient HCAECs via activation of caspase 3. Intercellular transfer of ceramide through lEVs was confirmed by use of a fluorescently labeled ceramide analogue. Treatment of HCAECs with a pharmacological inhibitor of nSMases (GW4869) or siRNA-mediated downregulation of nSMase2 abrogated the glucose-mediated effect on apoptosis in lEV-recipient cells. In contrast, for small EVs (sEVs), hyperglycemic injury or GW4869 treatment had no effect on apoptosis induction in sEV-recipient cells. CONCLUSION: lEVs mediate the induction of apoptosis in endothelial cells in response to hyperglycemic injury through intercellular transfer of ceramides.
Subject(s)
Carotid Artery Diseases/metabolism , Ceramides/metabolism , Diabetes Mellitus, Type 2/metabolism , Extracellular Vesicles/metabolism , Sphingomyelin Phosphodiesterase/physiology , Animals , Apoptosis , Cell Line , Endothelial Cells , Humans , Male , Mice , Mice, Inbred C57BLABSTRACT
Percutaneous mechanical circulatory support (pMCS) is increasingly used in patients with poor left-ventricular (LV) function undergoing elective high-risk percutaneous coronary interventions (HR-PCIs). These patients are often in critical condition and not suitable candidates for coronary artery bypass graft surgery. For the definition of HR-PCI, there is a growing consensus that multiple factors must be considered to define the complexity of PCI. These include haemodynamic status, left-ventricular ejection fraction, clinical characteristics, and concomitant diseases, as well as the complexity of the coronary anatomy/lesions. Although haemodynamic support by percutaneous LV assist devices is commonly adopted in HR-PCI (protected PCI), there are no clear guideline recommendations for indication due to limited published data. Therefore, decisions to use a nonsurgical, minimally invasive procedure in HR-PCI patients should be based on a risk-benefit assessment by a multidisciplinary team. Here, the current evidence and indications for protected PCI will be discussed.
ABSTRACT
Protected percutaneous coronary intervention is considered a life-saving procedure for high-risk patients. Therefore it is important that the interventional cardiology team is prepared, the procedure is planned, and potential complications, as well as bail out strategies are considered. Throughout the procedure, it is critical to monitor the patient to identify any early signs of deterioration or changes in patient well-being to avoid any potential complications.
ABSTRACT
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.
Subject(s)
Heart Failure , Heart Valve Prosthesis Implantation , Mitral Valve Insufficiency , Cardiac Catheterization/adverse effects , Heart Failure/surgery , Heart Valve Prosthesis Implantation/adverse effects , Humans , Mitral Valve/diagnostic imaging , Mitral Valve/surgery , Mitral Valve Insufficiency/diagnostic imaging , Mitral Valve Insufficiency/surgery , Treatment OutcomeABSTRACT
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.
Subject(s)
Aortic Valve Stenosis , Transcatheter Aortic Valve Replacement , Aortic Valve/diagnostic imaging , Aortic Valve/surgery , Aortic Valve Stenosis/diagnostic imaging , Aortic Valve Stenosis/surgery , Humans , Prospective Studies , Stroke Volume , Transcatheter Aortic Valve Replacement/adverse effects , Treatment Outcome , Ventricular Function, LeftABSTRACT
RATIONALE: Microvesicle-incorporated microRNAs (miRs) are biomarkers and effectors of cardiovascular disease. Whether microvesicle-miR expression is regulated in coronary artery disease (CAD) or not is unknown. OBJECTIVE: Here, we explore the expression of circulating microvesicle-miRs in patients with CAD and investigate the role of microvesicle-miR in endothelial cells. METHODS AND RESULTS: Circulating microvesicles were isolated from patients' plasma by using ultracentrifugation. Electron microscopy was used to determine the size of the microvesicles. A Taqman miR array revealed certain microvesicle-miRs are significantly regulated in patients with stable CAD compared with patients with ACS. To validate the miR array results, 180 patients with angiographically excluded CAD (n=41), stable CAD (n=77), and acute coronary syndrome (n=62) were prospectively studied. Nine miRs involved in regulation of vascular performance-miR-126-3p, miR-222-3p, miR-let-7d-5p, miR-21-5p, miR-26a-5p, miR-92a-3p, miR-139-5p, miR-30b-5p, and miR-199a-5p-were quantified in circulating microvesicles by real-time polymerase chain reaction (PCR). Among these, miR-92a-3p was significantly increased in patients with CAD compared with non-CAD patients. Microvesicle-sorting experiments showed endothelial cells (ECs) were the major cell source for microvesicles containing miR-92a-3p. In vitro oxLDL (oxidized low-density lipoprotein) and IL-6 (interleukin-6) stimulation increased miR-92a-3p expression in parent ECs and upregulated the expression level of endothelial microvesicle (EMV)-incorporated miR-92a-3p. Labeling of miR-92a-3p and EMVs demonstrated that functional miR-92a-3p was transported into recipient ECs, which accelerated cell migration and proliferation. Knockdown of miR-92a-3p in EMVs abrogated EMV-mediated effects on EC migration, proliferation, and blocked vascular network formation in a matrigel plug. Polymerase chain reaction-based gene profiling showed that the expression of THBS1 (thrombospondin 1) protein-a target of miR-92a-3p and an inhibitor of angiogenesis-was significantly reduced in ECs by EMVs. Knockdown of miR-92a-3p in EMVs abrogated EMV-mediated inhibition of the THBS1 gene and protein expression. CONCLUSIONS: Atherosclerotic conditions promote the packaging of endothelial miR-92a-3p into EMVs. EMV-mediated transfer of functional miR-92a-3p regulates angiogenesis in recipient ECs by a THBS1-dependent mechanism.
Subject(s)
Coronary Artery Disease/metabolism , Endothelium, Vascular/metabolism , Extracellular Vesicles/metabolism , MicroRNAs/metabolism , Plaque, Atherosclerotic/metabolism , Aged , Cells, Cultured , Coronary Artery Disease/pathology , Endothelium, Vascular/pathology , Female , Humans , Male , MicroRNAs/genetics , Middle Aged , Plaque, Atherosclerotic/pathologyABSTRACT
Transcatheter aortic valve replacement (TAVR) has emerged as a widely used therapy for aortic valve diseases. With TAVR, flow hemodynamics may change leading to areas of flow stagnation prone to thrombosis risk. The neo-sinus, created by introducing a prosthesis inside the diseased native valve, may prompt leaflet thrombosis due to areas of flow stasis. This study attempted to understand the effect of different prosthesis implant depths on the flow field within the neo- and native sinus and on the coronary perfusion. Experiments were performed inside an in vitro pulse duplicator producing physiological conditions according to ISO 5840-1:2015 standard. Flow fields were obtained for two cardiac outputs (CO) using particle image velocimetry (PIV). Washout was calculated as a measure of flow stasis. The two main results are: a lower implant position and a lower CO/frequency led to better native sinus washout, but worsened neo-sinus washout. In contrast, a higher implant position led to higher coronary flow (for higher CO/frequency). No significant effect of implant depth on coronary flow was observed for lower CO/frequency. In summary, a higher implant position using this self-expanding prosthesis is associated with reduced neo-sinus flow stasis. Hereby, washout of the native sinus, as well as coronary flow, are dependent on cardiac output.
Subject(s)
Aortic Valve Stenosis/surgery , Heart Valve Prosthesis/adverse effects , Models, Cardiovascular , Prosthesis Design , Transcatheter Aortic Valve Replacement/adverse effects , Aortic Valve/physiopathology , Aortic Valve/surgery , Aortic Valve Stenosis/physiopathology , Blood Flow Velocity , Cardiac Output , Coronary Circulation , Humans , Rheology , Transcatheter Aortic Valve Replacement/methods , Treatment OutcomeABSTRACT
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.
Subject(s)
Cardiovascular Agents/therapeutic use , Heart-Assist Devices , Intra-Aortic Balloon Pumping , Myocardial Infarction/therapy , Myocardial Revascularization , Shock, Cardiogenic/therapy , Aged , Cardiovascular Agents/adverse effects , Europe , Female , Heart-Assist Devices/adverse effects , Humans , Intra-Aortic Balloon Pumping/adverse effects , Intra-Aortic Balloon Pumping/mortality , Male , Middle Aged , Myocardial Infarction/complications , Myocardial Infarction/mortality , Myocardial Infarction/physiopathology , Myocardial Revascularization/adverse effects , Myocardial Revascularization/mortality , Prosthesis Design , Recovery of Function , Registries , Retrospective Studies , Risk Factors , Shock, Cardiogenic/etiology , Shock, Cardiogenic/mortality , Shock, Cardiogenic/physiopathology , Time Factors , Treatment OutcomeABSTRACT
Circulating sca1+/flk1+ cells are hypothesized to be endothelial progenitor cells (EPCs) in mice that contribute to atheroprotection by replacing dysfunctional endothelial cells. Decreased numbers of circulating sca1+/flk1+ cells correlate with increased atherosclerotic lesions and impaired reendothelialization upon electric injury of the common carotid artery. However, legitimate doubts remain about the identity of the putative EPCs and their contribution to endothelial restoration. Hence, our study aimed to establish a phenotype for sca1+/flk1+ cells to gain a better understanding of their role in atherosclerotic disease. In wild-type mice, sca1+/flk1+ cells were mobilized into the peripheral circulation by granulocyte-colony stimulating factor (G-CSF) treatment and this movement correlated with improved endothelial regeneration upon carotid artery injury. Multicolor flow cytometry analysis revealed that sca1+/flk1+ cells predominantly co-expressed surface markers of conventional B cells (B2 cells). In RAG2-deficient mice and upon B2 cell depletion, sca1+/flk1+ cells were fully depleted. In the absence of monocytes, sca1+/flk1+ cell levels were unchanged. A PCR array focused on cell surface markers and next-generation sequencing (NGS) of purified sca1+/flk1+ cells confirmed their phenotype to be predominantly that of B cells. Finally, the depletion of B2 cells, including sca1+/flk1+ cells, in G-CSF-treated wild-type mice partly abolished the endothelial regenerating effect of G-CSF, indicating an atheroprotective role for sca1+/flk1+ B2 cells. In summary, we characterized sca1+/flk1+ cells as a subset of predominantly B2 cells, which are apparently involved in endothelial regeneration.
Subject(s)
Antigens, Ly/metabolism , Atherosclerosis/metabolism , B-Lymphocyte Subsets/metabolism , Carotid Artery Injuries/metabolism , Carotid Artery, Common/metabolism , Cell Proliferation , Endothelial Progenitor Cells/metabolism , Membrane Proteins/metabolism , Re-Epithelialization , Vascular Endothelial Growth Factor Receptor-2/metabolism , Animals , Antigens, Ly/genetics , Atherosclerosis/genetics , Atherosclerosis/immunology , Atherosclerosis/pathology , B-Lymphocyte Subsets/immunology , B-Lymphocyte Subsets/pathology , Carotid Artery Injuries/genetics , Carotid Artery Injuries/immunology , Carotid Artery Injuries/pathology , Carotid Artery, Common/immunology , Carotid Artery, Common/pathology , DNA-Binding Proteins/deficiency , DNA-Binding Proteins/genetics , Disease Models, Animal , Endothelial Progenitor Cells/immunology , Endothelial Progenitor Cells/pathology , Female , Lymphocyte Depletion , Male , Membrane Proteins/genetics , Mice, Inbred C57BL , Mice, Knockout , Phenotype , Signal Transduction , Vascular Endothelial Growth Factor Receptor-2/geneticsABSTRACT
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.
Subject(s)
Atrial Function, Left , Atrial Remodeling , Cardiac Catheterization/instrumentation , Heart Failure/physiopathology , Heart Valve Prosthesis Implantation/instrumentation , Heart Valve Prosthesis , Mitral Valve Insufficiency/surgery , Mitral Valve/surgery , Aged , Aged, 80 and over , Cardiac Catheterization/adverse effects , Chronic Disease , Echocardiography, Three-Dimensional , Female , Heart Failure/diagnostic imaging , Heart Valve Prosthesis Implantation/adverse effects , Humans , Male , Mitral Valve/diagnostic imaging , Mitral Valve/physiopathology , Mitral Valve Insufficiency/diagnostic imaging , Mitral Valve Insufficiency/physiopathology , Prospective Studies , Recovery of Function , Time Factors , Treatment OutcomeABSTRACT
BACKGROUND: Transcatheter aortic valve replacement (TAVR) is an alternative treatment option to surgical aortic valve replacement (SAVR) in selected high-risk patients. In this study, we aimed to evaluate the prognostic value of right ventricular (RV) functional imaging to predict clinical response to TAVR and SAVR. METHODS: One hundred and ten patients with symptomatic severe aortic valve stenosis (AVS) undergoing successful TAVR and 32 controls undergoing SAVR were prospectively enrolled. Six months follow up (FU) included two-dimensional (2D) transthoracic echocardiography (TTE) with RV deformation imaging. RESULTS: Baseline TTE showed no significant differences between groups (TAVR and SAVR) in conventional left ventricular (LV) and RV functional parameters (LV ejection fraction [LV-EF]: p = .21; tricuspidal annular plane systolic excursion [TAPSE]: 1.8 ± 0.5 cm, 1.9 ± 0.4 cm, p = .21), and RV strain (right ventricular-global longitudinal strain [RV-GLS] -11.6 ± 5.2%, -11.5 ± 6.5%, p = .70). At FU LV function was unchanged in both groups (p > .05); RV function was significantly improved after TAVR (RV-GLS: -11.6 ± 5.2%, -13.4 ± 6.1%, p = .005; TAPSE: 1.8 ± 0.5 cm, 1.9 ± 0.3 cm, p = .05), and worsened after SAVR (RV-GLS: -11.5 ± 6.5%, -8.9 ± 5.2%, p = .04; TAPSE: 1.9 ± 0.4 cm, 1.5 ± 0.3 cm, p < .001). Functional New York Heart Association (NYHA) class remained unchanged in patients after SAVR (p = .21), and improved after TAVR (p < .001). Baseline RV function was linked with clinical response to TAVR (TAPSE, p < .0001; RV-GLS, p = .04), and the development of RV-GLS was associated with functional worsening after SAVR (p = .05). CONCLUSION: Baseline RV function and changes of right heart mechanics are closely associated with functional improvements after AVR. SAVR, but not TAVR, seems to have detrimental effects on RV-function.
Subject(s)
Aortic Valve Stenosis/surgery , Aortic Valve/surgery , Echocardiography, Doppler , Heart Valve Prosthesis Implantation , Transcatheter Aortic Valve Replacement , Ventricular Function, Right , Aged , Aged, 80 and over , Aortic Valve/diagnostic imaging , Aortic Valve/physiopathology , Aortic Valve Stenosis/diagnostic imaging , Aortic Valve Stenosis/physiopathology , Biomechanical Phenomena , Case-Control Studies , Female , Heart Valve Prosthesis Implantation/adverse effects , Humans , Male , Predictive Value of Tests , Prospective Studies , Recovery of Function , Severity of Illness Index , Time Factors , Transcatheter Aortic Valve Replacement/adverse effects , Treatment Outcome , Ventricular Function, LeftABSTRACT
OBJECTIVES: The purpose of this study was to investigate the impact of periprocedural troponin levels on clinical outcome following the MitraClip procedure. BACKGROUND: Cardiac troponin is known to be a predictive biomarker for various clinical outcomes; however, data about its predictive value in patients undergoing transcatheter mitral valve repair are limited. METHODS: Consecutive patients undergoing the MitraClip procedure were enrolled. Serum cardiac troponin I concentrations were measured before and after the procedure, and the maximal value recorded within 72 hr after the procedure was used for the postprocedural values. The clinical outcome was all-cause mortality within a 1-year follow-up. RESULTS: Out of 354 patients, 29 patients (8.2%) were deceased within 1 year. Patients who died had significantly higher baseline (0.05 [0.01-0.08] vs. 0.01 [0.01-0.03] ng/ml; p < .001) and postprocedural troponin I values (0.51 [0.30-1.42] vs. 0.20 [0.33-0.55] ng/ml; p = .005). A Kaplan-Meier analysis showed that patients with higher baseline troponin I values had a significantly worse prognosis than those with lower values (log-rank p < .001), and similarly, 1-year mortality was significantly higher in patients with higher postprocedural troponin I than those with lower levels (log-rank p = .021). Moreover, the highest mortality rate was observed in patients with both elevated baseline and postprocedural troponin I values (log-rank p = .001), which was found to be an independent predictor of mortality by multivariable analyses. CONCLUSIONS: The present study suggests that combined baseline and postprocedural troponin measurements are useful for risk stratification of 1-year mortality following the MitraClip procedure.
Subject(s)
Cardiac Catheterization/instrumentation , Heart Valve Prosthesis Implantation/instrumentation , Heart Valve Prosthesis , Mitral Valve Insufficiency/surgery , Mitral Valve/surgery , Postoperative Complications/blood , Troponin I/blood , Aged , Aged, 80 and over , Biomarkers/blood , Cardiac Catheterization/adverse effects , Cardiac Catheterization/mortality , Female , Heart Valve Prosthesis Implantation/adverse effects , Heart Valve Prosthesis Implantation/mortality , Humans , Male , Mitral Valve/diagnostic imaging , Mitral Valve/physiopathology , Mitral Valve Insufficiency/diagnostic imaging , Mitral Valve Insufficiency/physiopathology , Postoperative Complications/diagnosis , Postoperative Complications/mortality , Predictive Value of Tests , Prosthesis Design , Risk Assessment , Risk Factors , Time Factors , Treatment Outcome , Up-RegulationABSTRACT
BACKGROUND: In the continuity equation, assumption of a round-shaped left ventricular outflow tract (LVOT) leads to underestimation of the true aortic valve area in two-dimensional echocardiography. The current study evaluated whether inclusion of the LVOT area, as measured by computed tomography (CT), reclassifies the degree of aortic stenosis (AS) and assessed the impact on patient outcome after transcatheter aortic valve replacement (TAVR). METHODS AND RESULTS: Four hundred and twenty-two patients with indexed aortic valve area index (AVAi) of <0.6 cm2 /m2 , assessed by using the classical continuity equation (mean age: 81.5 ± 6.1 years, 51% female, mean left ventricular ejection fraction: 53.2 ± 13.6%), underwent TAVR and were included. After inclusion of the CT measured LVOT area into the continuity equation, the hybrid AVAi led to a reclassification of 30% (n = 128) of patients from severe to moderate AS. Multivariate predictors for reclassification were male sex, lower mean aortic gradient, and lower annulus/LVOT ratio (all p < .01). Reclassified patients had significantly higher sST2 at baseline and higher NT-proBNP values at baseline and 6 months follow-up compared to non-reclassified patients. Acute kidney injury was experienced more frequently after TAVR by reclassified patients, but no significant mortality difference occurred during 2 years of follow-up. CONCLUSION: The hybrid AVAi reclassifies a significant portion of low-gradient severe AS patients into moderate AS. Reclassified patients showed increased fibrosis and heart failure markers at baseline compared to non-reclassified patients. But reclassification had no significant impact on mortality up to 2 years after TAVR. Routine assessment of hybrid AVAi seems not to improve further risk stratification of TAVR patients.
Subject(s)
Aortic Valve Stenosis/surgery , Aortic Valve/surgery , Decision Support Techniques , Echocardiography, Doppler, Pulsed , Multidetector Computed Tomography , Transcatheter Aortic Valve Replacement , Aged , Aged, 80 and over , Aortic Valve/diagnostic imaging , Aortic Valve/physiopathology , Aortic Valve Stenosis/diagnostic imaging , Aortic Valve Stenosis/mortality , Aortic Valve Stenosis/physiopathology , Clinical Decision-Making , Female , Humans , Male , Postoperative Complications/mortality , Predictive Value of Tests , Recovery of Function , Registries , Retrospective Studies , Risk Assessment , Risk Factors , Severity of Illness Index , Time Factors , Transcatheter Aortic Valve Replacement/adverse effects , Transcatheter Aortic Valve Replacement/mortality , Treatment OutcomeABSTRACT
OBJECTIVE: The DanGer Shock trial test the hypothesis that left ventricular (LV) mechanical circulatory support with Impella CP transvalvular microaxial flow pump improves survival in patients with ST segment elevation acute myocardial infarction complicated by cardiogenic shock (AMICS) compared to conventional guideline-driven treatment. This paper describes the rationale and design of the randomized trial, in addition to the baseline characteristics of the population screened and enrolled so far. METHODS: The DanGer Shock study is a prospective, multicenter, open-label trial in patients with AMICS randomized 1:1 to Impella CP or current guideline-driven therapy with planned enrollment of 360 patients. Patients comatose after out of hospital cardiac arrest are excluded. Eligible patients are randomized immediately following shock diagnosis. Among patients randomized to receive Impella CP, the device is placed prior to angioplasty. The primary endpoint is all-cause mortality at 180 days. Baseline characteristics of patients screened and randomized in the DanGer Shock as of June 2018 are compared with 2 contemporary AMICS studies. RESULTS: As of end of June 2018, 314 patients were screened and 100 patients were randomized. Patients had median arterial lactate of 5.5 mmol/L (interquartile range 3.7-8.8 mmol/L), median systolic blood pressure of 76 mmHg (interquartile range 70-88 mmHg), and median LV ejection fraction of 20% (interquartile range 10%-30%). CONCLUSION: The DanGer Shock trial will be the first adequately powered randomized trial to address whether mechanical circulatory LV support with Impella CP can improve survival in AMICS. Baseline characteristics of the first 100 randomized patients indicate a population in profound cardiogenic shock.