Efficient and Modular Biofunctionalization of Thiophene-Based Conjugated Polymers through Embedded Latent Disulfide.

Biofunctionalized conjugated polymers (i.e., carrying enzymes, antibodies, and nucleic acids) are of great interest for many biological applications, yet efficient biofunctionalization of conjugated polymers under biocompatible conditions is challenging. We report a facile strategy to make biofunctionalized conjugated polymers through thiol-ene chemistry with embedded latent disulfide functional groups. This is made possible through the design of a cyclic disulfide-containing dioxythiophene, which can be integrated into a series of conjugated polymers via acid-catalyzed chain-growth polymerization. The utility of such a biofunctionalized polymer with glucose oxidase has been examined in organic electrochemical transistors for the selective sensing of glucose. This work provides a venue for the creation of biofunctional organic semiconductors.

Cardiac wasting in patients with cancer.

Patients with cancer face a significant risk of cardiovascular death, regardless of time since cancer diagnosis. Elderly patients are particularly more susceptible as cancer-associated cardiac complications present in advanced stage cancer. These patients may often present with symptoms observed in chronic heart failure (HF). Cardiac wasting, commonly observed in these patients, is a multifaceted syndrome characterized by systemic metabolic alterations and inflammatory processes that specifically affect cardiac function and structure. Experimental and clinical studies have demonstrated that cancer-associated cardiac wasting is linked with cardiac atrophy and altered cardiac morphology, which impairs cardiac function, particularly pertaining to the left ventricle. Therefore, this review aims to present a summary of epidemiologic data and pathophysiological mechanisms of cardiac wasting due to cancer, and future directions in this field.

Amphiregulin in infectious diseases: Role, mechanism, and potential therapeutic targets.

Amphiregulin (AREG) serves as a ligand for the epidermal growth factor receptor (EGFR) and is involved in vital biological functions, including inflammatory responses, tissue regeneration, and immune system function. Upon interaction with the EGFR, AREG initiates a series of signaling cascades necessary for several physiological activities, such as metabolism, cell cycle regulation, and cellular proliferation. Recent findings have provided evidence for the substantial role of AREG in maintaining the equilibrium of homeostasis in damaged tissues and preserving epithelial cell structure in the context of viral infections affecting the lungs. The development of resistance to influenza virus infection depends on the presence of type 1 cytokine responses. Following the eradication of the pathogen, the lungs are subsequently colonized by several cell types that are linked with type 2 immune responses. These cells contribute to the process of repairing and resolving the tissue injury and inflammation caused by infections. Following influenza infection, the activation of AREG promotes the regeneration of bronchial epithelial cells, enhancing the tissue's structural integrity and increasing the survival rate of infected mice. In the same manner, mice afflicted with influenza experience rapid mortality due to a subsequent bacterial infection in the pulmonary region when both bacterial and viral infections manifest concurrently inside the same host. The involvement of AREG in bacterial infections has been demonstrated. The gene AREG experiences increased transcriptional activity inside host cells in response to bacterial infections caused by pathogens such as Escherichia coli and Neisseria gonorrhea. In addition, AREG has been extensively studied as a mitogenic stimulus in epithelial cell layers. Consequently, it is regarded as a prospective contender that might potentially contribute to the observed epithelial cell reactions in helminth infection. Consistent with this finding, mice that lack the AREG gene exhibit a delay in the eradication of the intestinal parasite Trichuris muris. The observed delay is associated with a reduction in the proliferation rate of colonic epithelial cells compared to the infected animals in the control group. The aforementioned findings indicate that AREG plays a pivotal role in facilitating the activation of defensive mechanisms inside the epithelial cells of the intestinal tissue. The precise cellular sources of AREG in this specific context have not yet been determined. However, it is evident that the increased proliferation of the epithelial cell layer in infected mice is reliant on CD4+ T cells. The significance of this finding lies in its demonstration of the crucial role played by the interaction between immunological and epithelial cells in regulating the AREG-EGFR pathway. Additional research is necessary to delve into the cellular origins and signaling mechanisms that govern the synthesis of AREG and its tissue-protective properties, independent of infection.

The potential impact of renin-angiotensin system inhibitors on cancer survival and recurrence: A systemic review and meta-analysis.

Renin-angiotensin-system inhibitors (RASi), specifically angiotensin-converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARBs), are widely used anti-hypertensives. Their impact on the prognostic outcomes among cancer patients has been subject to scrutiny and debate. The aim of this study is to evaluate the effect of RASi on survival in cancer patients. We systematically searched PubMed, Web of Science, Embase and Cochrane Library for relevant studies published until April 1st, 2022. All the studies, interventional or observational, which examined effects of ARBs and ACEi on cancer prognosis compared to a control group and reported the survival outcomes and Hazards Ratios were included in the analysis. From each study, pooled hazard ratios (HR) with corresponding 95% confidence intervals (95% CI) were identified and collected. Subgroup analysis was conducted to investigate heterogeneity. Sixty-one studies were included in this meta-analysis. Data of 343,283 participants were used in the study. It was found that RASi improved overall survival (OS) (HR=0.88; 95% CI: 0.82-0.93; P<0.0001), progression free survival (PFS) (HR=0.72; 95% CI: 0.65-0.79; P<0.00001), disease specific survival (DSS) (HR=0.86; 95% CI: 0.71-1.04; P=0.03), and recurrence free survival (RFS) (HR=0.74; 95% CI: 0.58-0.93; P=0.01) in cancer patients. The effect of RASi on OS varied depending on the type of cancer or type of RASi (ACEi or ARBs), according to subgroup analysis. The usage of RAS inhibitors has a positive impact on survival outcomes and recurrence among cancer patients.

Predictive significance of pretreatment 18F-FDG PET volumetric parameters on survival outcomes in pediatric patients with locally advanced undifferentiated nasopharyngeal carcinoma.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is a rare pediatric cancer. Most children are first diagnosed with advanced locoregional disease. Identification of patients at higher risk of treatment failure is crucial as they may benefit from more aggressive initial treatment approaches. 18Fluorine-labeled fluoro-2-deoxyglucose positron emission tomography (18F-FDG PET) has shown promise as a prognostic tool for predicting outcomes. METHODS: Retrospective study of pediatric patients with locally advanced undifferentiated NPC who underwent 18F-FDG PET/CT prior to intial treatment. Predictive significance of metabolic PET parameters on survival outcomes were estimated. RESULTS: Thirty-two children were included, age range was 7.1-18 years at the time of diagnosis. The median follow-up duration was 46.1 months. Three patients (9.4%) were classified as AJCC stage IIb, 13 patients (40.6%) as stage IIIa, eight patients (25%) as stage IIIb, and eight patients (25%) as stage IVa. Our findings revealed that high whole-body metabolic tumor volume at the threshold of hepatic reference SUVmean (WB-MTV-HR) (>135 mL) was associated with significantly lower event-free survival (EFS) compared to the low WB-MTV-HR group (≤135 mL) (3-year EFS: 50% ± 18% vs. 82% ± 8%; p = .015). Additionally, the 3-year overall survival (OS) rates differed significantly between the high whole-body metabolic tumor volume at the threshold of an SUV of 2.5 isocontour (WB-MTV-2.5) group (MTV >74 mL) and the low WB-MTV-2.5 group (MTV ≤74 mL) (63% ± 18% vs. 100%; p = .021). CONCLUSION: Our study suggests that WB-MTV parameters could serve as significant prognostic factors for disease progression in pediatric patients with locally advanced undifferentiated NPC. However, further prospective studies with larger sample sizes are needed to validate these findings.

Safety and efficacy of Withania somnifera for anxiety and insomnia: Systematic review and meta-analysis.

OBJECTIVE: Despite the historical neurological use of Withania somnifera, limited evidence supports its efficacy for conditions like anxiety and insomnia. Given its known anti-stress properties, this review evaluated its safety and efficacy for anxiety and insomnia. METHODS: We searched Medline, Cochrane Library, and Google Scholar until August 2023 for randomized controlled trials (RCTs) comparing W. somnifera to placebo in patients with anxiety and/or insomnia. Outcome measures included changes in anxiety levels via the Hamilton Anxiety Scale (HAM-A), Sleep Onset Latency (SOL), Total Sleep Time (TST), Wake After Sleep Onset (WASO), Total Time in Bed (TIB), Sleep Efficiency (SE), and Pittsburgh Sleep Quality Index (PSQI) score. We utilized a random-effect model for pooling Mean Differences (MD) with a 95% Confidence Interval (CI). Heterogeneity was assessed through sensitivity and subgroup analysis, and the quality of RCTs was evaluated using the Cochrane revised risk of bias tool. RESULTS: Pooled results from five RCTs (n = 254) demonstrated that W. somnifera significantly reduced HAM-A scores (MD = -5.96; [95% CI -10.34, -1.59]; P = 0.008; I2 = 98%), as well as sleep parameters such as SOL, TST, PSQI, and SE, but not WASO and TIB. CONCLUSION: While W. somnifera extracts yielded promising results, further research with larger sample sizes is needed to confirm its effects on anxiety and insomnia.

Temporary mechanical support in the peripartum patient as a bridge to postpartum recovery: A report of three cases.

Cardiogenic shock (CS) is a severe complication of peripartum cardiomyopathy (PPCM). Patients with deteriorating CS often require temporary mechanical circulatory support. In PPCM, this can be used as a bridge to postpartum recovery or bridge to decision. The outcomes are unclear, especially if prolonged utilization is required. We present a case series of three patients with PPCM in deteriorating CS who were successfully supported with a ventricular assist device or veno-arterial extracorporeal membrane oxygenation as a bridge to postpartum recovery.

Use of fusion imaging in safe, rapid, and accurate placement of percutaneous right ventricular assist device in the management of acute post-surgical right ventricular failure.

Fusion imaging (FI) technology using EchoNavigator that integrates live transesophageal echocardiogram and overlays on real-time fluoroscopy. We present our experience placing a right ventricular (RV) support device, a ProtekDuo, in our patient with post-operative RV failure using FI to guide the implantation.

Paclitaxel-Coated Balloon vs Uncoated Balloon for Coronary In-Stent Restenosis: The AGENT IDE Randomized Clinical Trial.

Importance: Drug-coated balloons offer a potentially beneficial treatment strategy for the management of coronary in-stent restenosis. However, none have been previously evaluated or approved for use in coronary circulation in the United States. Objective: To evaluate whether a paclitaxel-coated balloon is superior to an uncoated balloon in patients with in-stent restenosis undergoing percutaneous coronary intervention. Design, Setting, and Participants: AGENT IDE, a multicenter randomized clinical trial, enrolled 600 patients with in-stent restenosis (lesion length <26 mm and reference vessel diameter >2.0 mm to ≤4.0 mm) at 40 centers across the United States between May 2021 and August 2022. One-year clinical follow-up was completed on October 2, 2023. Interventions: Participants were randomized in a 2:1 allocation to undergo treatment with a paclitaxel-coated (n = 406) or an uncoated (n = 194) balloon. Main Outcomes and Measures: The primary end point of 1-year target lesion failure-defined as the composite of ischemia-driven target lesion revascularization, target vessel-related myocardial infarction, or cardiac death-was tested for superiority. Results: Among 600 randomized patients (mean age, 68 years; 157 females [26.2%]; 42 Black [7%], 35 Hispanic [6%] individuals), 574 (95.7%) completed 1-year follow-up. The primary end point at 1 year occurred in 17.9% in the paclitaxel-coated balloon group vs 28.6% in the uncoated balloon group, meeting the criteria for superiority (hazard ratio [HR], 0.59 [95% CI, 0.42-0.84]; 2-sided P = .003). Target lesion revascularization (13.0% vs 24.7%; HR, 0.50 [95% CI, 0.34-0.74]; P = .001) and target vessel-related myocardial infarction (5.8% vs 11.1%; HR, 0.51 [95% CI, 0.28-0.92]; P = .02) occurred less frequently among patients treated with paclitaxel-coated balloon. The rate of cardiac death was 2.9% vs 1.6% (HR, 1.75 [95% CI, 0.49-6.28]; P = .38) in the coated vs uncoated balloon groups, respectively. Conclusions and Relevance: Among patients undergoing coronary angioplasty for in-stent restenosis, a paclitaxel-coated balloon was superior to an uncoated balloon with respect to the composite end point of target lesion failure. Paclitaxel-coated balloons are an effective treatment option for patients with coronary in-stent restenosis. Trial Registration: ClinicalTrials.gov Identifier: NCT04647253.

Reductive Doping Inhibits the Formation of Isomerization-Derived Structural Defects in N-doped Poly(benzodifurandione) (n-PBDF).

Recently, solution-processable n-doped poly(benzodifurandione) (n-PBDF) has been made through in-situ oxidative polymerization and reductive doping, which exhibited exceptionally high electrical conductivities and optical transparency. The discovery of n-PBDF is considered a breakthrough in the field of organic semiconductors. In the initial report, the possibility of structural defect formation in n-PBDF was proposed, based on the observation of structural isomerization from (E)-2H,2'H-[3,3'-bibenzofuranylidene]-2,2'-dione (isoxindigo) to chromeno[4,3-c]chromene-5,11-dione (dibenzonaphthyrone) in the dimer model reactions. In this study, we present clear evidence that structural isomerization is inhibited during polymerization. We reveal that the dimer (BFD1) and the trimer (BFD2) can be reductively doped by several mechanisms, including hydride transfer, forming charge transfer complexes (CTC) or undergoing an integer charge transfer (ICT) with reactants available during polymerization. Once the hydride transfer adducts, the CTC, or the ICT product forms, structural isomerization can be effectively prevented even at elevated temperatures. Our findings provide a mechanistic understanding of why isomerization-derived structural defects are absent in n-PBDF backbone. It lays a solid foundation for the future development of n-PBDF as a benchmark polymer for organic electronics and beyond.

Severe cardiogenic shock and cardiac arrest due to fulminant cardiac sarcoidosis: a case report.

BACKGROUND: Cardiac sarcoidosis is found to occur in approximately 5% of patients with sarcoidosis. Its presentation can typically range from complete heart block to ventricular arrhythmias. This condition can rarely present with severe heart failure and cardiogenic shock requiring aggressive and timely management strategies. Advanced imaging techniques are usually required to assist with its diagnosis. CASE PRESENTATION: A 70-year-old woman with a history of pulmonary sarcoidosis presented with non-ST elevation myocardial infarction, congestive hepatopathy, and acute renal failure. Left heart catheterization showed evidence of non-obstructive coronary artery disease, and right heart catheterization revealed severely elevated filling pressures and depressed cardiac index. She underwent aggressive diuresis and placement of an intra-aortic balloon pump in addition to initiation of inotropic and vasopressor support. While in the cardiac intensive care unit, she experienced frequent episodes of ventricular tachycardia and went into cardiac arrest requiring cardiopulmonary resuscitation. High clinical suspicion for cardiac sarcoidosis was confirmed by cardiac magnetic resonance imaging findings. After starting immunosuppressive therapy for cardiac sarcoidosis, she demonstrated clinical improvement. CONCLUSION: Patients with cardiac sarcoidosis may remain asymptomatic or present with conduction abnormalities and arrhythmias. They rarely present with severe biventricular heart failure and cardiogenic shock, and in such cases, they require timely initiation of pharmacologic and device therapies, along with implementation of mechanical circulatory support.

Protein Contaminants Matter: Building Universal Protein Contaminant Libraries for DDA and DIA Proteomics.

Mass spectrometry-based proteomics is constantly challenged by the presence of contaminant background signals. In particular, protein contaminants from reagents and sample handling are almost impossible to avoid. For data-dependent acquisition (DDA) proteomics, an exclusion list can be used to reduce the influence of protein contaminants. However, protein contamination has not been evaluated and is rarely addressed in data-independent acquisition (DIA). How protein contaminants influence proteomic data is also unclear. In this study, we established new protein contaminant FASTA and spectral libraries that are applicable to all proteomic workflows and evaluated the impact of protein contaminants on both DDA and DIA proteomics. We demonstrated that including our contaminant libraries can reduce false discoveries and increase protein identifications, without influencing the quantification accuracy in various proteomic software platforms. With the pressing need to standardize proteomic workflow in the research community, we highly recommend including our contaminant FASTA and spectral libraries in all bottom-up proteomic data analysis. Our contaminant libraries and a step-by-step tutorial to incorporate these libraries in various DDA and DIA data analysis platforms can be valuable resources for proteomic researchers, freely accessible at https://github.com/HaoGroup-ProtContLib.

Impact of Laparoscopic Sleeve Gastrectomy on Cardiovascular Pharmacotherapy in Left Ventricular Assist Device Patients.

ABSTRACT: Left ventricular assist device (LVAD) implantation is increasingly utilized in patients with advanced heart failure and morbid obesity. Laparoscopic sleeve gastrectomy (LSG) can facilitate weight loss in this population and can ultimately change the pharmacokinetics of heart failure therapeutics. In this study, we aimed to explore the changes in cardiovascular pharmacotherapy post LSG intervention. We conducted a retrospective observational cohort study of morbidly obese LVAD patients between 2013 and 2019 at the University of Florida with available pharmacotherapeutic data at 1 and 6 months. Thirteen post-LSG patients and 13 control subjects were included in the final analysis. In the post-LSG group, the mean body mass index decreased significantly (44 ± 5 vs. 34 ± 4.9, P < 0.001), and 7 patients were successfully bridged to cardiac transplantation. Only 3 patients required adjustment of their LVAD speed. Mean return to flow decreased by 8 mm Hg, despite a 45% reduction in the mean number of vasodilators per patient (1.2 vs. 0.7, P = 0.03). Mean weekly warfarin dose decreased by 35% after 6 months (32.9 ± 20.9 vs. 50.7 ± 26.6, P = 0.01). The use of diuretics, vasodilators, and beta-blockers was significantly reduced by 50%, 45%, and 35%, respectively. None of these changes were observed in the control group at 6-month follow-up post LVAD. In this single-center experience, weight loss post LSG is associated with decreased vasodilator, diuretic, and anticoagulant medication requirements in LVAD patients.

Early prediction of hemodialysis complications employing ensemble techniques.

BACKGROUND AND OBJECTIVES: Hemodialysis complications remain a critical threat among dialysis patients. They result in sudden termination of the session which impacts the efficiency of dialysis. As intra-dialytic complications are the result of the interplay of multiple factors, artificial intelligence can aid in their early prediction. This research aims to compare different machine learning tools for the early prediction of the most frequent hemodialysis complications with high performance, using the fewest predictors for easier practical implementation. METHODS: Fifty different variables were recorded during 6000 hemodialysis sessions performed in a regional dialysis unit in Egypt. The filter technique was used to extract the most relevant features. Then, five individual classifiers and three ensemble approaches were implemented to predict the occurrence of intra-dialytic complications. Different subsets of 25, 12 and 6 from the 50 collected features were tested. RESULTS: Random forest yielded the highest accuracy of 98% with the least training time using 12 features in a balanced dataset, while the gradient boosting allowed obtaining the highest F1-score of 94%, 92%, and 78% in the prediction of hypotension, hypertension, and dyspnea, respectively, in imbalanced datasets. CONCLUSION: Applying different machine learning algorithms to big datasets can improve accuracy, reduce training time and model complexity allowing simple implementation in clinical practice. Our models can help nephrologists predict and possibly prevent dialysis complications.

Echocardiography for extracorporeal membrane oxygenation.

Extracorporeal membrane oxygenation (ECMO) provides advanced cardiopulmonary life support for patients in cardiac and/or respiratory failure. Echocardiography provides essential diagnostic and anatomic information prior to ECMO initiation, allows for safe and efficient ECMO cannula positioning, guides optimization of flow, provides a modality for rapid troubleshooting and patient evaluation, and facilitates decision-making for eventual weaning of ECMO support. Currently, guidelines for echocardiographic assessment in this clinical context are lacking. In this review, we provide an overview of echocardiographic considerations for advanced imagers involved in the care of these complex patients. We focus predominately on new cannulas and complex cannulation techniques, including a special focus on double lumen cannulas and a section discussing indirect left ventricular venting. Echocardiography is tremendously valuable in providing optimal care in these challenging clinical situations. It is imperative for imaging physicians to understand the pertinent anatomic considerations, the often complicated physiological and hemodynamic context, and the limitations of the imaging modality.

Bivalirudin as a Systemic Anticoagulant and Flush Solution Additive for Sequential Mitral and Tricuspid Valve Percutaneous Edge-to-Edge Repair in a Patient With Heparin-Induced Thrombocytopenia.

Herein the case of a patient with a prior history of heparin-induced thrombocytopenia who underwent percutaneous mitral valve edge-to-edge repair that was followed by a tricuspid edge-to-edge repair two months later is presented. Recommendations exist for systemic anticoagulant alternatives for percutaneous mitral valve edge-to-edge repair with the MitraClip device (Abbott, Chicago, IL), but minimal guidance and experience are present regarding alternative systemic anticoagulation during the performance of right-sided interventions, including tricuspid edge-to-edge repair (TriClip; Abbott). Notably, there is no clear consensus regarding the use of an alternative anticoagulant in the catheter flush solution for the delivery systems used during these procedures, particularly for right-sided interventions.

Fixed-dose aspirin monotherapy compared with thromboelastography directed antiplatelet therapy in long-term management of left ventricular assist devices.

BACKGROUND AND AIM: The role of thromboelastography (TEG) in managing antiplatelet therapy (APT) in left ventricular assist devices (LVADs) is controversial. Our aim was to determine whether removal of TEG from an LVAD-specific APT protocol reduced late-onset bleeding without increasing thromboembolic complications. METHODS: We performed a single-center, retrospective cohort study including all recipients of a continuous-flow LVAD between April 2005 and November 2019 (n = 293). LVAD recipients before June 1, 2017 (n = 221) whose APT was monitored and adjusted using TEG were compared with LVAD recipients after June 1, 2017 (n = 72) where TEG was not utilized. Occurrence of late-onset bleeding events after postoperative Day 7 and thromboembolic events were collected. APT doses, warfarin use and International normalized ratio (INR) values were collected at discharge and at 1, 3, 6, and 12-months postimplantation. RESULTS: Over a median 12-month follow-up, INTERMACS major bleeding events occurred in 35% of patients where TEG was utilized compared with 29% where TEG was not utilized (p = 0.375), and procedural intervention was required in 29% compared with 18%, respectively (p = 0.058). Use of TEG was associated with higher doses of aspirin (>325 mg) (41% compared with none) and use of a second antiplatelet (dipyridamole) (43% compared to 1%). Despite this, there was no significant difference in thromboembolic events (15% in each). CONCLUSIONS: Our study suggests the use of TEG led to increased doses of aspirin as well as adding a second antiplatelet agent, without improving outcomes in LVAD recipients. Furthermore, the removal of TEG from an LVAD-specific APT protocol did not worsen thromboembolic outcomes.

Effectiveness of Autologous Fat Transfer in the Treatment of Scar-Related Conditions: A Systematic Review and Meta-analysis.

BACKGROUND AND AIM: Autologous fat transfer (AFT) has been introduced as a potential treatment option for scar-tissue and its related symptoms. However, the scientific evidence for its effectiveness remains unclear. This meta-analysis aims to evaluate the available evidence regarding the effectiveness of autologous fat transfer for the treatment of scar-tissue and its related conditions. METHODS: PubMed/Medline database was queried from its inception till the end of November 2021. All the relevant studies assessing the effect of autologous fat transfer in the treatment of scar-related conditions were pooled in using a random-effects model. RESULTS: 9 studies (n=179) were included in the meta-analysis. Pooled analysis demonstrates significant improvement in all subscales of the POSAS patient score with most prominent in color 2.4 points (95% CI 1.78-3.041), stiffness 2.9 points (95% CI 2.33-3.45), irregularity 2.2 points (95% CI 1.093-3.297) and thickness 1.8 points (95% CI 0.804-2.719), respectively. Pain and itch improved relatively lesser, 1.3 points (95% CI 0.958-1.674) and 0.6 points (95% CI 0.169-1.215), respectively. The POSAS observer scale showed a relatively lower improvement with the least in vascularity 0.5 points (95% CI 0.098-0.96), pigmentation 0.8 points (95% CI 0.391-1.276) and surface area 0.8 points (95% CI 0.34-1.25). Thickness improved by 1.4 points (95% CI 0.582-2.3), relief 1.0 points (95% CI 0.461-1.545) and pliability 1.5 points (95% CI 1.039-2.036). CONCLUSION: Our findings demonstrate that autologous fat transfer (AFT) is a promising treatment for scar-related conditions as it provides beneficial results in the scar quality. Future research should focus on the long-term effects of AFT and high-level evidence studies such as, randomized controlled trials (RCTs) and cohort studies are required. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Hemodynamic effects of ivabradine use in combination with intravenous inotropic therapy in advanced heart failure.

Intravenous inotropic therapy can be used in patients with advanced heart failure, as palliative therapy or as a bridge to cardiac transplantation or mechanical circulatory support, as well as in cardiogenic shock. Their use is limited to increasing cardiac output in low cardiac output states and reducing ventricular filling pressures to alleviate patient symptoms and improve functional class. Many advanced heart failure patients have sinus tachycardia as a compensatory mechanism to maintain cardiac output. However, excessive sinus tachycardia caused by intravenous inotropes can increase myocardial oxygen consumption, decrease coronary perfusion, and at extreme heart rates decrease ventricular filling and stroke volume. The limited available hemodynamic studies support the hypothesis that adding ivabradine, a rate control agent without negative inotropic effect, may blunt inotrope-induced tachycardia and its associated deleterious effects, while optimizing cardiac output by increasing stroke volume. This review analyzes the intriguing pathophysiology of combined intravenous inotropes and ivabradine to optimize the hemodynamic profile of patients in advanced heart failure. Graphical abstract Illustration of the beneficial and deleterious hemodynamic effects of intravenous inotropes in advanced heart failure, and the positive effects of adding ivabradine.

Incremental value of three-dimensional transesophageal echocardiography over the two-dimensional technique in the assessment of a partially detached MitraClip.

We describe an elderly male patient with two MitraClip devices, one fixed and the other detached, in whom live/real-time three-dimensional echocardiography (3DTEE) provided incremental value and additional information compared to two-dimensional transesophageal echocardiography (2DTEE). 3DTEE offered the ability to comprehensively assess the mitral valve (MV) utilizing full volume and multiplanar reconstruction (MPR) modes. 3DTEE proved useful in assessing the position of the properly attached and the partially detached MitraClip, including assessment of orifice size and degree of mitral regurgitation (MR). In addition, trapping of MV chordae by both clips was noted in the 3DTEE image dataset and confirmed at the time of surgery. Chordal trapping was not detected by 2DTEE. 3DTEE proved useful in more accurately estimating the severity of residual MR with the MitraClips in place since the regurgitant jet vena contracta (VC) could be viewed en face and VC area measured by planimetry in the correct imaging plane as compared to limited linear images from 2DTEE.