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The article presents a study which evaluates the effectiveness of prolonged glucocorticoid treatment (PGCT) in patients having an acute lung injury as well as acute respiratory distress syndrome (ARDS). It shows that PGCT at low-to-moderate doses has not been associated with an increased rate of huge complications such as infections and neuromyopathy. It is concluded that glucocorticoid treatment is effective and safe treatment for several infections.

Aortic blood flow patterns are closely linked to the morphology and function of the left ventricle, aortic valve and aorta. These flow patterns demonstrate the exceptional adaptability of the cardiovascular system to maintain blood circulation under a broad range of haemodynamic workloads and can be altered in various pathophysiological states. For instance, normal ascending aortic systolic flow is predominantly laminar, whereas abnormal aortic systolic flow is associated with increased eccentricity, vorticity and flow reversal. These flow abnormalities result in reduced aortic conduit function and increased energy loss in the cardiovascular system. Emerging evidence details the association of these flow patterns with loss of aortic compliance, which leads to adverse left ventricular remodelling, poor tissue perfusion, and an increased risk of morbidity and death. In this Perspective article, we review the evidence for the link between aortic flow-related abnormalities and cardiovascular disease and how these changes in aortic flow patterns are emerging as a therapeutic target for aortic valve intervention in first-in-human studies., (© 2023. Springer Nature Limited.)

Primary or secondary tricuspid regurgitation (TR) represents an important health care burden and challenge which has often been neglected or undertreated in the past. The expansion and reinforcement of the indications for tricuspid valve (TV) intervention in the 2017 editions of the guidelines as well as the introduction of transcatheter tricuspid valve intervention (TTVI) has considerably increased the attention of the community on the TV and the volume of TV interventions in the past years. Depending on the anatomic target, TTVI can be categorized as the following: 1) direct or indirect tricuspid restrictive annuloplasty; 2) direct (edge-to-edge repair) or indirect (coaptation device) restoration of leaflet coaptation; 3) heterotopic tricuspid valve implantation; and 4) transcatheter tricuspid valve replacement. Multimodality imaging has crucial role for the following: 1) patient selection for TTVI and procedure planning; 2) guiding and monitoring the procedure; and 3) assessing and following over time the results of the procedure. The key points for pre-procedural imaging are: 1) accurate quantitation of TR severity; 2) proper identification of the mechanism(s) responsible for the TR; and 3) quantitation of RV dysfunction and pulmonary arterial hypertension. This imaging work-up is essential to select the right type of intervention for the right patient and TV. Transesophageal echocardiography and fluoroscopy imaging is also key for guiding the TTVI procedures and fusion between these 2 modalities may further enhance the quality of procedure guiding., Competing Interests: Author Disclosures Dr. Pibarot has received funding from Edwards Lifesciences for echocardiography corelab analyses in the field of transcatheter valve therapies with no personal compensation. Dr. Rodés-Cabau is a consultant for and has received institutional research grants from V-Wave. Dr. Maisano is a consultant for Abbott Vascular, ValtechCardio, Medtronic, Edwards Lifesciences, and Apica; is a founder of 4Tech; and has received royalties from Edwards Lifesciences. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: After 3 years of continuous-flow left ventricular assist device (CF-LVAD) support, nearly a third of patients develop at least moderate aortic insufficiency (AI). Percutaneous occluder devices, surgical aortic valve replacement (SAVR), and urgent heart transplantation are available treatment options. Transcatheter aortic valve replacement (TAVR) has not been widely used for treating symptomatic AI in patients on LVAD support., Methods: Retrospective chart review and data analysis from October 2010 through August 2017 was performed. A total of 286 patients with end-stage heart failure (ESHF) were implanted with a durable CF-LVAD. Nine patients subsequently developed significant symptomatic AI, which was treated with TAVR., Results: All 9 patients had 1 TAVR procedure with resolution of AI and were discharged home. Procedural complications include valve migration warranting a second valve for stabilization, retroperitoneal and groin hematoma, and pseudoaneurysm requiring thrombin injection. A significant improvement of the New York Heart Association classification was noted from the time of implant to 6 months. Two patients had unplanned heart failure‒related hospitalizations within 6 months. At 6 months, 89% of patients were alive on LVAD support., Conclusions: TAVR is a successful treatment modality for LVAD patients who develop symptomatic AI., (Copyright © 2019 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Importance: Transcatheter aortic valve replacement (TAVR) is established for selected patients with severe aortic stenosis. However, limitations such as suboptimal deployment, conduction disturbances, and paravalvular leak occur., Objective: To evaluate if a mechanically expanded valve (MEV) is noninferior to an approved self-expanding valve (SEV) in high-risk patients with aortic stenosis undergoing TAVR., Design, Setting, and Participants: The REPRISE III trial was conducted in 912 patients with high or extreme risk and severe, symptomatic aortic stenosis at 55 centers in North America, Europe, and Australia between September 22, 2014, and December 24, 2015, with final follow-up on March 8, 2017., Interventions: Participants were randomized in a 2:1 ratio to receive either an MEV (n = 607) or an SEV (n = 305)., Main Outcomes and Measures: The primary safety end point was the 30-day composite of all-cause mortality, stroke, life-threatening or major bleeding, stage 2/3 acute kidney injury, and major vascular complications tested for noninferiority (margin, 10.5%). The primary effectiveness end point was the 1-year composite of all-cause mortality, disabling stroke, and moderate or greater paravalvular leak tested for noninferiority (margin, 9.5%). If noninferiority criteria were met, the secondary end point of 1-year moderate or greater paravalvular leak was tested for superiority in the full analysis data set., Results: Among 912 randomized patients (mean age, 82.8 [SD, 7.3] years; 463 [51%] women; predicted risk of mortality, 6.8%), 874 (96%) were evaluable at 1 year. The primary safety composite end point at 30 days occurred in 20.3% of MEV patients and 17.2% of SEV patients (difference, 3.1%; Farrington-Manning 97.5% CI, -∞ to 8.3%; P = .003 for noninferiority). At 1 year, the primary effectiveness composite end point occurred in 15.4% with the MEV and 25.5% with the SEV (difference, -10.1%; Farrington-Manning 97.5% CI, -∞ to -4.4%; P<.001 for noninferiority). The 1-year rates of moderate or severe paravalvular leak were 0.9% for the MEV and 6.8% for the SEV (difference, -6.1%; 95% CI, -9.6% to -2.6%; P < .001). The superiority analysis for primary effectiveness was statistically significant (difference, -10.2%; 95% CI, -16.3% to -4.0%; P < .001). The MEV had higher rates of new pacemaker implants (35.5% vs 19.6%; P < .001) and valve thrombosis (1.5% vs 0%) but lower rates of repeat procedures (0.2% vs 2.0%), valve-in-valve deployments (0% vs 3.7%), and valve malpositioning (0% vs 2.7%)., Conclusions and Relevance: Among high-risk patients with aortic stenosis, use of the MEV compared with the SEV did not result in inferior outcomes for the primary safety end point or the primary effectiveness end point. These findings suggest that the MEV may be a useful addition for TAVR in high-risk patients., Trial Registration: ClinicalTrials.gov Identifier: NCT02202434.

Background: Transcatheter mitral valve replacement (TMVR) is a potential therapy for patients with symptomatic, severe mitral regurgitation (MR). The feasibility of this therapy remains to be defined., Objectives: The authors report their early experience with TMVR using a new valve system., Methods: The valve is a self-expanding, nitinol valve with bovine pericardial leaflets that is placed using a transapical delivery system. Patients with symptomatic MR who were deemed high or extreme risk by the local heart teams were enrolled in a global pilot study at 14 sites (United States, Australia, and Europe)., Results: Fifty consecutively enrolled patients (mean age: 73 ± 9 years; 58.0% men; 84% secondary MR) underwent TMVR with the valve. The mean Society for Thoracic Surgery score was 6.4 ± 5.5%; 86% of patients were New York Heart Association functional class III or IV, and the mean left ventricular ejection fraction was 43 ± 12%. Device implant was successful in 48 patients with a median deployment time of 14 min (interquartile range: 12 to 17 min). The 30-day mortality was 14%, with no disabling strokes, or repeat interventions. Median follow-up was 173 days (interquartile range: 54 to 342 days). At latest follow-up, echocardiography confirmed mild or no residual MR in all patients who received implants. Improvements in symptom class (79% in New York Heart Association functional class I or II at follow-up; p < 0.0001 vs. baseline) and Minnesota Heart Failure Questionnaire scores (56.2 ± 26.8 vs. 31.7 ± 22.1; p = 0.011) were observed., Conclusions: TMVR with the valve was feasible in a study group at high or extreme risk for conventional mitral valve replacement. These results inform trial design of TMVR in lower-risk patients with severe mitral valve regurgitation (Evaluation of the Safety and Performance of the Twelve Intrepid Transcatheter Mitral Valve Replacement System in High Risk Patients with Severe, Symptomatic Mitral Regurgitation - The Twelve Intrepid TMVR Pilot Study; NCT02322840)., (Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: This study aimed to develop a procedure simulation platform for in vitro transcatheter aortic valve replacement (TAVR) using patient-specific 3-dimensional (3D) printed tissue-mimicking phantoms. We investigated the feasibility of using these 3D printed phantoms to quantitatively predict the occurrence, severity, and location of any degree of post-TAVR paravalvular leaks (PVL)., Background: We have previously shown that metamaterial 3D printing technique can be used to create patient-specific phantoms that mimic the mechanical properties of biological tissue. This may have applications in procedural planning for cardiovascular interventions., Methods: This retrospective study looked at 18 patients who underwent TAVR. Patient-specific aortic root phantoms were created using the tissue-mimicking 3D printing technique using pre-TAVR computed tomography. The CoreValve (self-expanding valve) prostheses were deployed in the phantoms to simulate the TAVR procedure, from which post-TAVR aortic root strain was quantified in vitro. A novel index, the annular bulge index, was measured to assess the post-TAVR annular strain unevenness in the phantoms. We tested the comparative predictive value of the bulge index and other known predictors of post-TAVR PVL., Results: The maximum annular bulge index was significantly different among patient subgroups that had no PVL, trace-to-mild PVL, and moderate-to-severe PVL (p = 0.001). Compared with other known PVL predictors, bulge index was the only significant predictor of moderate-severe PVL (area under the curve = 95%; p < 0.0001). Also, in 12 patients with post-TAVR PVL, the annular bulge index predicted the major PVL location in 9 patients (accuracy = 75%)., Conclusions: In this proof-of-concept study, we have demonstrated the feasibility of using 3D printed tissue-mimicking phantoms to quantitatively assess the post-TAVR aortic root strain in vitro. A novel indicator of the post-TAVR annular strain unevenness, the annular bulge index, outperformed the other established variables and achieved a high level of accuracy in predicting post-TAVR PVL, in terms of its occurrence, severity, and location., (Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Outcomes with bivalirudin compare favorably with heparin ± GPIIb/IIIa receptor inhibition (heparin ± GPI) during percutaneous coronary intervention (PCI). Patients with congestive heart failure (CHF) have increased risk for complications. The objective was to investigate clinical and economic outcomes for bivalirudin ± GPI vs. heparin ± GPI among PCI patients with CHF., Methods: Using the Premier Hospital Database, PCI patients with CHF were stratified by anticoagulant: bivalirudin, bivalirudin ± GPI, heparin and heparin ± GPI. The probability of receiving bivalirudin ± GPI was estimated using individual and hospital variables. Using propensity scores, each bivalirudin ± GPI patient was matched to a heparin ± GPI patient. The primary outcome was in-hospital death. Bleeding rates, transfusion, length of stay and in-hospital cost were ascertained., Results: Overall, 116,313 patients at 315 hospitals received bivalirudin (n = 45,559) bivalirudin + GPI (n = 8,115), heparin (n = 27,972) or heparin + GPI (n = 34,667). Patients had STEMI (21.2%), NSTEMI (29.1%), unstable angina (16.6%), stable angina (5.7%) or other ischemic heart disease (24.2%). Of these, 79.1% of bivalirudin patients matched, resulting in 84,948 analyzed patients. Compared with heparin ± GPI patients, bivalirudin ± GPI patients had fewer deaths (3.3% vs. 3.9%; p < 0.0001), less clinically apparent bleeding (10.2% vs. 11.4%; p < 0.0001), clinically apparent bleeding with transfusion (2.7% vs. 3.2%, p <0.0001), and transfusion (8.5% vs. 9.8%, p < 0.0001). Patients receiving bivalirudin had shorter length of stay (6.3 vs. 6.8 days; p < 0.0001) and lower in-hospital cost (mean $26,706 vs. $27,166 [median $19,414 vs. $19,798]; p < 0.0001). In conclusion, this is the largest retrospective analysis of PCI patients with CHF and demonstrates bivalirudin ± GPI compared with heparin ± GPI is associated with lower inpatient rates of death, bleeding, and cost., (© 2015 Wiley Periodicals, Inc.)

Clinical studies have shown positive associations among sustained and intense inflammatory responses and the incidence of bacterial infections. Patients presenting with acute respiratory distress syndrome (ARDS) and high levels of proinflammatory cytokines, such as tumor necrosis factor alpha (TNF-alpha), interleukin 1 beta (IL-1 beta), and IL-6, have increased risk for developing nosocomial infections attributable to organisms such as Staphylococcus aureus, Pseudomonas aeruginosa, and Acinetobacter spp., compared to those patients with lower levels. Our previous in vitro studies have demonstrated that these bacterial strains exhibit enhanced growth extracellularly when supplemented with high concentrations of pure recombinant TNF-alpha, IL-1 beta, or IL-6. In addition, we have shown that the intracellular milieu of phagocytic cells that are exposed to supraoptimal concentrations of TNF-alpha, IL-1 beta, and IL-6 or lipopolysaccharide (LPS) favors survival and replication of ingested bacteria. Therefore, we hypothesized that under conditions of intense inflammation the host's micromilieu favors bacterial infections by exposing phagocytic cells to protracted high levels of inflammatory cytokines. Our clinical studies have shown that methylprednisolone is capable of reducing the levels of TNF-alpha, IL-1 beta, and IL-6 in ARDS patients. Hence, we designed a series of in vitro experiments to test whether human monocytic cells (U937 cells) that are activated with high concentrations of LPS, which upregulate the release of proinflammatory cytokines from these phagocytic cells, would effectively kill or restrict bacterial survival and replication after exposure to methylprednisolone. Fresh isolates of S. aureus, P. aeruginosa, and Acinetobacter were used in our studies. Our results indicate that, compared with the control, stimulation of U937 cells with 100-ng/ml, 1.0-microg/ml, 5.0-microg/ml, or 10.0-microg/ml concentrations of LPS enhanced the intracellular survival and replication of all three species of bacteria significantly (for all, P = 0.0001). Stimulation with < or =10.0 ng of LPS generally resulted in efficient killing of the ingested bacteria. Interestingly, when exposed to graded concentrations of methylprednisolone, U937 cells that had been stimulated with 10.0 microg of LPS were able to suppress bacterial replication efficiently in a concentration-dependent manner. Significant reduction in numbers of CFU was observed at > or =150 microg of methylprednisolone per ml (P values were 0.032, 0.008, and 0.009 for S. aureus, P. aeruginosa, and Acinetobacter, respectively). We have also shown that steady-state mRNA levels of TNF-alpha, IL-1 beta, and IL-6 in LPS-activated cells were reduced by treatment of such cells with methylprednisolone, in a concentration-dependent manner. The effective dose of methylprednisolone was 175 mg, a value that appeared to be independent of priming level of LPS and type of mRNA. We therefore postulate that a U-shaped relationship exists between the level of expression of TNF-alpha, IL-1 beta, and IL-6 within the phagocytic cells and their abilities to suppress active survival and replication of phagocytized bacteria.