Biosensors with left ventricular assist devices.

Heart failure imposes a significant global health burden, standing as a primary contributor to mortality. Various indicators and physiological shifts within the body may hint at distinct cardiac conditions. Specific biosensors have the capability to identify these changes. Integrating or embedding these biosensors into mechanical circulatory support devices (MCSDs), such as left ventricular assist devices (LVADs), becomes crucial for monitoring alterations in biochemical and physiological factors subsequent to an MCSD implantation. Detecting abnormal changes early in the course of disease progression will allow for improved patient outcomes and prognosis following an MCSD implantation. The aim of this review is to explore the available biosensors that may be coupled or implanted alongside LVADs to monitor biomarkers and changes in physiological parameters. Different fabrication materials for the biosensors are discussed, including their advantages and disadvantages. This review also examines the feasibility of integrating feedback control mechanisms into LVAD systems using data from the biosensors. Challenges facing this emerging technology and future directions for research and development are outlined as well. The overarching goal is to provide an overview of how implanted biosensors may improve the performance and outcomes of LVADs through continuous monitoring and closed-loop control.

Large animal models to study effectiveness of therapy devices in the treatment of heart failure with preserved ejection fraction (HFpEF).

Our understanding of the complex pathophysiology of Heart failure with preserved ejection fraction (HFpEF) is limited by the lack of a robust in vivo model. Existing in-vivo models attempt to reproduce the four main phenotypes of HFpEF; ageing, obesity, diabetes mellitus and hypertension. To date, there is no in vivo model that represents all the haemodynamic characteristics of HFpEF, and only a few have proven to be reliable for the preclinical evaluation of potentially new therapeutic targets. HFpEF accounts for 50% of all the heart failure cases and its incidence is on the rise, posing a huge economic burden on the health system. Patients with HFpEF have limited therapeutic options available. The inadequate effectiveness of current pharmaceutical therapeutics for HFpEF has prompted the development of device-based treatments that target the hemodynamic changes to reduce the symptoms of HFpEF. However, despite the potential of device-based solutions to treat HFpEF, most of these therapies are still in the developmental stage and a relevant HFpEF in vivo model will surely expedite their development process. This review article outlines the major limitations of the current large in-vivo models in use while discussing how these designs have helped in the development of therapy devices for the treatment of HFpEF.

Advancements in left ventricular assist devices to prevent pump thrombosis and blood coagulopathy.

Mechanical circulatory support (MCS) devices, such as left ventricular assist devices (LVADs) are very useful in improving outcomes in patients with advanced-stage heart failure. Despite recent advances in LVAD development, pump thrombosis is one of the most severe adverse events caused by LVADs. The contact of blood with artificial materials of LVAD pumps and cannulas triggers the coagulation cascade. Heat spots, for example, produced by mechanical bearings are often subjected to thrombus build-up when low-flow situations impair washout and thus the necessary cooling does not happen. The formation of thrombus in an LVAD may compromise its function, causing a drop in flow and pumping power leading to failure of the LVAD, if left unattended. If a clot becomes dislodged and circulates in the bloodstream, it may disturb the flow or occlude the blood vessels in vital organs and cause internal damage that could be fatal, for example, ischemic stroke. That is why patients with LVADs are on anti-coagulant medication. However, the anti-coagulants can cause a set of issues for the patient-an example of gastrointestinal (GI) bleeding is given in illustration. On account of this, these devices are only used as a last resort in clinical practice. It is, therefore, necessary to develop devices with better mechanics of blood flow, performance and hemocompatibility. This paper discusses the development of LVADs through landmark clinical trials in detail and describes the evolution of device design to reduce the risk of pump thrombosis and achieve better hemocompatibility. Whilst driveline infection, right heart failure and arrhythmias have been recognised as LVAD-related complications, this paper focuses on complications related to pump thrombosis, especially blood coagulopathy in detail and potential strategies to mitigate this complication. Furthermore, it also discusses the LVAD implantation techniques and their anatomical challenges.

A European update on transcatheter aortic valve implantation (TAVI) in the COVID era.

Minimally invasive approaches for aortic valve replacement are now at the forefront of pathological aortic valve treatment. New trials show comparability of these devices to existing therapies, not only in high-risk surgical cohorts but also in low-risk and intermediate-risk cohorts. This review provides vital clinical and anatomical background to aortic valvular disease treatment guidelines, while also providing an update on transcatheter aortic valve implantation (TAVI) devices in Europe, their interventional trials and associated complications.

In vitro benchtop mock circulatory loop for heart failure with preserved ejection fraction emulation.

In this work, a novel mock circulatory loop (MCL) is presented that is capable of simulating both healthy cardiac function and Heart Failure with preserved Ejection Fraction (HFpEF). This MCL differs from others presented in the literature as it features two independently actuated heart chambers, representing the left atrium and the left ventricle. This is an important improvement over other designs as it allows for potential HFpEF treatments to be examined, not just in relation to their effect on the left ventricle but also on the left atrium. The aim of this work was to show that novel MCL designs could be developed to allow for testing of new mechanical circulatory support devices for the treatment of HFpEF. Two loop configurations are presented, one featuring hard PVC cylindrical chambers and one that features soft silicone chambers which are anatomically analogous to the native heart. We show that both MCLs are capable of simulating the onset of HFpEF with a sustained increase in diastolic pressure of 62.03% and a sustained decrease in end diastolic volume (EDV) of 14.24%.

Diuretic therapy in congestive heart failure.

In heart failure, fluid overload is a major pathological mechanism leading to vascular congestion, pulmonary congestion and elevated jugular venous pressures. Diuretics play a significant role in the management of patients with congestive heart failure. It is used to relieve the congestive symptoms of heart failure. However, the appropriate use of diuretics remains challenging due to various complications like electrolyte abnormalities, worsening renal function and diuretic resistance. This has prompted towards the search of safer and effective alternatives. This review evaluates the use of diuretics in congestive heart failure and discusses the complications of different types of diuretics, which is essential for successful management of congestion in patients with heart failure and hence to optimise the outcome for the patients.

Device-Based Solutions to Improve Cardiac Physiology and Hemodynamics in Heart Failure With Preserved Ejection Fraction.

Characterized by a rapidly increasing prevalence, elevated mortality and rehospitalization rates, and inadequacy of pharmaceutical therapies, heart failure with preserved ejection fraction (HFpEF) has motivated the widespread development of device-based solutions. HFpEF is a multifactorial disease of various etiologies and phenotypes, distinguished by diminished ventricular compliance, diastolic dysfunction, and symptoms of heart failure despite a normal ejection performance; these symptoms include pulmonary hypertension, limited cardiac reserve, autonomic imbalance, and exercise intolerance. Several types of atrial shunts, left ventricular expanders, stimulation-based therapies, and mechanical circulatory support devices are currently under development aiming to target one or more of these symptoms by addressing the associated mechanical or hemodynamic hallmarks. Although the majority of these solutions have shown promising results in clinical or preclinical studies, no device-based therapy has yet been approved for the treatment of patients with HFpEF. The purpose of this review is to discuss the rationale behind each of these devices and the findings from the initial testing phases, as well as the limitations and challenges associated with their clinical translation.

Interesting presentation of a broad complex tachycardia during the head up tilt table test.

Broad complex tachycardia (BCT) during head up tilt test (HUTT) is infrequent. Electrophysiology Study (EPS) plays an important part in further differentiation of BCT. We present a case of BCT during HUTT in a patient presenting with presyncope which later on EPS with 3D mapping was diagnosed as ventricular tachycardia. This case highlights the unusual occurrence of BCT during HUTT, the differential diagnosis of BCT and the utility of EPS to reliably identify the type and origin of BCT.

A multidirectional two-tube method for chemical pleurodesis could improve distribution of the sclerosing agent within the pleural cavity - A pilot study.

INTRODUCTION: Malignant pleural effusion (MPE) affects approximately 200,000 people in the United States per annum. Chemical pleurodesis is a recommended first line treatment in the management of MPE, however, success rates as low as 43% has been reported. A bedside chemical pleurodesis can cost up to $11,224 and an estimated inpatient annual expenditure of more than $5 billion in the US alone. This study aims to assess the distribution of the talc slurry within the pleural space using human cadaveric models and to determine the force required to push the talc slurry though a 14 Fr chest tube. MATERIALS AND METHODS: The force required to administer the talc slurry through a 14 Fr chest tube was tested using a Zwick/Roelle Z005 mechanical tester, using a porcine thoracic biomodel. Talc slurry distribution within the pleural cavity was assessed by direct visualisation following administration to the human cadaveric models using single and multidirectional two-tube methods. RESULTS: Maximum force required to push the talc slurry through a 14 Fr chest tube was 11.36 N ± 2.79 N. Distribution of the talc slurry within the pleural cavity was found to be poor with a single tube method. Multidirectional two-tube method of administration showed more even distribution. CONCLUSION: The experimental multidirectional two-tube method results in wider distribution of the talc slurry within the pleural cavity and could further improve success rate of the talc pleurodesis.

The role of anti-inflammatory drugs and nanoparticle-based drug delivery models in the management of ischemia-induced heart failure.

Ongoing advancements in the treatment of acute myocardial infarction (MI) have significantly decreased MI related mortality. Consequently, the number of patients experiencing post-MI heart failure (HF) has continued to rise. Infarction size and the extent of left ventricular (LV) remodeling are largely determined by the extent of ischemia at the time of myocardial injury. In the setting of MI or acute phase of post-MI LV remodeling, anti-inflammatory drugs including intravenous immunoglobulin (IVIG) and Pentoxifylline have shown potential efficacy in preventing post-MI remodeling in-vitro and in some clinical trials. However, systemic administration of anti-inflammatory drugs are not without their off-target side effects. Herein, we explore the clinical feasibility of targeted myocardial delivery of anti-inflammatory drugs via biodegradable polymers, liposomes, hydrogels, and nano-particle based drug delivery models (NDDM) based on existing pre-clinical and clinical models. We summarize the barriers to clinical application of targeted anti-inflammatory delivery post-MI, including challenges in achieving sufficient retention and distribution, as well as the potential need for multiple dosing. Collectively, we suggest that localized delivery of anti-inflammatory agents to the myocardium using NDDM is a promising approach for successful treatment of ischemic HF. Future studies will be instrumental in determining the most effective target and delivery modalities for orchestrating NDDM-mediated treatment of HF.

Resveratrol significantly improves cell survival in comparison to dexrazoxane and carvedilol in a h9c2 model of doxorubicin induced cardiotoxicity.

Cancer is one of the leading causes of deaths worldwide with 18.1 million deaths per year. Although there have been significant advances in anti-cancer therapies, they can often result in side effects with cardiovascular complications being the most severe. Dexrazoxane is the only currently approved treatment for prevention of anthracycline induced cardiotoxicity but there are concerns about its use due to the development of secondary malignancies and myelodysplastic syndrome. Additionally, it is only recommended in patients who are due to receive a total cumulative dose of 300 mg/m2 of doxorubicin or 540 mg/m2 of epirubicin. Thus, there exists an urgent need to develop new therapeutic strategies to counteract anthracycline induced cardiotoxicity. The h9c2 cardiomyoblast was investigated for its differentiation capacity and used to screen and compare promising prophylactics for doxorubicin induced cardiotoxicity. The half maximal inhibitory concentration of doxorubicin was determined in differentiated h9c2 cells after 24 h of exposure, to establish a model for drug screening. Cells were treated with dexrazoxane, resveratrol, and carvedilol either 3 h or 24 h prior to doxorubicin treatment. The ability of these cardioprotectants to prevent cardiotoxicity was analysed using the cck-8 cell viability assay and the dichlorofluorescin diacetate (DCFDA) reactive oxygen species (ROS) assay. There was no significant increase in survival in treatment groups after 3 h, however, at 24 h, resveratrol significantly improved survival compared to all other groups (p < 0.05). Additionally, dexrazoxane and resveratrol significantly decreased ROS formation at 3 h (p < 0.05) and all groups significantly decreased ROS production at 24 h (p < 0.001). This work is the first comparison of these cardioprotectants and suggests that resveratrol may be a more effective treatment in the prevention of anthracycline induced cardiotoxicity, compared to dexrazoxane and carvedilol. However, further work will be needed in order to decipher the exact mechanism and potential of this drug in the clinic.

Towards the use of localised delivery strategies to counteract cancer therapy-induced cardiotoxicities.

Cancer therapies have significantly improved cancer survival; however, these therapies can often result in undesired side effects to off target organs. Cardiac disease ranging from mild hypertension to heart failure can occur as a result of cancer therapies. This can warrant the discontinuation of cancer treatment in patients which can be detrimental, especially when the treatment is effective. There is an urgent need to mitigate cardiac disease that occurs as a result of cancer therapy. Delivery strategies such as the use of nanoparticles, hydrogels, and medical devices can be used to localise the treatment to the tumour and prevent off target side effects. This review summarises the advancements in localised delivery of anti-cancer therapies to tumours. It also examines the localised delivery of cardioprotectants to the heart for patients with systemic disease such as leukaemia where localised tumour delivery might not be an option.

The Spectrum of Non-ischemic Cardiac Magnetic Resonance Imaging Findings: A Retrospective Analysis.

Introduction Since cardiac pathologies remain ubiquitous, their prompt diagnosis through the means of innovative technologies, such as cardiac magnetic resonance imaging, remains pivotal. The spectrum of these pathologies varies widely, ranging from ischemic etiologies to rare cardiac malignancies. This study evaluates the prevalence of nonischemic cardiac pathologies, such as infiltrative heart diseases, that often warrant meticulous diagnostic evaluation through the means of cardiac magnetic resonance imaging. Methods We performed a retrospective study in order to analyse the cardiac magnetic resonance imaging records of 250 patients over a period of six months with previously remarkable cardiac histories. Patients with a prior history of ischemic cardiac disease, as determined from past medical and surgical records, were excluded from the study. The prevalence of various nonischemic findings was ascertained. The demographic characteristics and comorbidities of the patients were also tabulated.  Results In the present study, 250 patients were included, of which 115 were females and 135 were males, with the mean age hovering at 48.21 ± 11.49 years. The top two most prevalent cardiac magnetic resonance imaging findings were concentric moderate-to-severe left ventricular hypertrophy and patchy subendocardial late gadolinium enhancement of the left ventricle; these were observed in 62.2% and 23.7% of the patients, respectively. Cardiac magnetic resonance imaging also divulged findings typical of rarer pathologies, including cardiac sarcoidosis and primary cardiac lymphoma. Conclusion Pathologies of the heart often mandate extensive diagnostic workup through the means of radiological modalities such as cardiac magnetic resonance imaging. In patients with indications of nonischemic cardiac pathologies, cardiac magnetic resonance imaging can be employed as part of the initial radiological armamentarium. Furthermore, cardiac magnetic resonance remains the imaging modality of choice for detecting infrequent cardiac pathologies, such as cardiac sarcoidosis.

An organosynthetic dynamic heart model with enhanced biomimicry guided by cardiac diffusion tensor imaging.

The complex motion of the beating heart is accomplished by the spatial arrangement of contracting cardiomyocytes with varying orientation across the transmural layers, which is difficult to imitate in organic or synthetic models. High-fidelity testing of intracardiac devices requires anthropomorphic, dynamic cardiac models that represent this complex motion while maintaining the intricate anatomical structures inside the heart. In this work, we introduce a biorobotic hybrid heart that preserves organic intracardiac structures and mimics cardiac motion by replicating the cardiac myofiber architecture of the left ventricle. The heart model is composed of organic endocardial tissue from a preserved explanted heart with intact intracardiac structures and an active synthetic myocardium that drives the motion of the heart. Inspired by the helical ventricular myocardial band theory, we used diffusion tensor magnetic resonance imaging and tractography of an unraveled organic myocardial band to guide the design of individual soft robotic actuators in a synthetic myocardial band. The active soft tissue mimic was adhered to the organic endocardial tissue in a helical fashion using a custom-designed adhesive to form a flexible, conformable, and watertight organosynthetic interface. The resulting biorobotic hybrid heart simulates the contractile motion of the native heart, compared with in vivo and in silico heart models. In summary, we demonstrate a unique approach fabricating a biomimetic heart model with faithful representation of cardiac motion and endocardial tissue anatomy. These innovations represent important advances toward the unmet need for a high-fidelity in vitro cardiac simulator for preclinical testing of intracardiac devices.

Anti-malarial, cytotoxicity and molecular docking studies of quinolinyl chalcones as potential anti-malarial agent.

The quinolinyl chalcones series (A1-A14) were screened for antimalarial activity. According to in vitro antimalarial studies, many quinolinyl chalcones are potentially active against CQ-sensitive and resistance P. falciparum strains with no toxicity against Vero cell lines. The most active quinolinyl chalcones A4 (with IC50 0.031 µM) made a stable A4-heme complex with - 25 kcal/mole binding energy and also showed strong π-π interaction at 3.5 Å. Thus, the stable A4-heme complex formation suggested that these quinolinyl chalcones act as a blocker for heme polymerization. The docking results of quinolinyl chalcones with Pf-DHFR showed that the halogenated benzene part of quinolinyl chalcones made strong interaction with Pf-DHFR as compared to quinoline part. A strong A4-Pf-DHFR complex was formed with low binding energy (- 11.04 kcal/mole). The ADMET properties of quinolinyl chalcones were also studied. The in vivo antimalarial studies also confirmed the A4 as an active antimalarial agent.

Insulin-like growth factor-1 (IGF-1) poly (lactic-co-glycolic acid) (PLGA) microparticles - development, characterisation, and in vitro assessment of bioactivity for cardiac applications.

Aim: The aim of this study was to evaluate the formulation of a synthetic IGF-1 (pIGF-1) in PLGA microparticles (MP). Methods: Poly (lactic-co-glycolic acid) (PLGA) MPs loaded with pIGF-1 were prepared, characterised and evaluated using double emulsion solvent evaporation method. Results: Spherical MPs showed an average particle size of 2 µm, encapsulation efficiency (EE) of 67% and 50% degradation over 15 days. With a view to enhancing retention in the myocardium, the MP formulation was encapsulated in a cross-linked hyaluronic acid hydrogel. pIGF-1 released from MPs and from MPs suspended in hyaluronic acid hydrogel remained bioactive, determined by a significant increase in cellular proliferation of c-kit+ cells. Conclusion: This formulation has potential for loco-regional delivery to damaged myocardium to promote the survival of cardiomyocytes.

Recent Trends in Clot Retrieval Devices: A Review.

Stroke is the second leading cause of death worldwide and in Europe. Even with gold standard medical management of acute ischemic stroke, which is intravenous (IV) thrombolysis by administration of recombinant tissue plasminogen activator (rt-PA), the mortality rate remains the same. Intra-arterial (IA) thrombolysis therapy also did not achieve significant results and was not approved by the US Food and Drug Administration (FDA) because of limited sample size. This encouraged scientists and engineers to develop endovascular clot retrieval devices for the mechanical recanalization of the occluded arteries in stroke patients. Although the initial designs of clot retrieval devices failed, efforts to improve these devices continue. Recently clot retrieval devices were approved by the FDA as first-line treatment along with IV rt-PA. This article gives an in-depth review of different clot retrieval devices which includes MERCI (the first), the Penumbra Aspiration System, EmboTrap®II, stent retrievers, and the way forward with the new FDA clearance of the devices as first-line treatment for acute ischemic stroke along with IV rt-PA. The review also includes a comparison of clot retrieval devices to gold standard treatment.