BACKGROUND: Heart failure is a major worldwide health concern and leading cause of mortality. RNAi interventions hold promise for patients resistant to conventional drugs due to their off-target effects and lack of specificity.
OBJECTIVE: To examine the safety and effectiveness of RNAi therapeutics in treating heart failure.
METHODS: The PubMed, Embase, Scopus and Cochrane databases were searched using appropriate keyword from inception until December 31, 2023. A total of 14 studies fulfilling predefined selection criteria were included for qualitative synthesis.
RESULTS: We found that in patients with cardiac amyloidosis, patisiran and revusiran showed considerable improvements in cardiac output and left ventricular wall thickness. In animal studies, Nox2-siRNA showed effectiveness in regaining heart function. Furthermore, cardiomyocyte count and left ventricular function were improved by DUSP5 siRNA + T3 therapy and meg3 inhibition after myocardial infarction (MI). RNAi showed minimal adverse effects like peripheral neuropathy, hepatotoxicity, urinary tract infection, vaginal infection, diarrhea, abdominal pain arrhythmias, conduction disorders, and cardiotoxicity (LV wall thinning, heart failure) and improved cardiac biomarkers.
CONCLUSIONS: RNAi therapeutics are novel treatment option for improving cardiac function because their high target specificity, ability to target genes that conventional drugs struggle to reach and potential for long-lasting effects. Further research on optimizing delivery methods, improving target specificity, evaluating long-term safety profiles and cost-effectiveness to fully realize their potential.

UNASSIGNED: Atomoxetine, a selective norepinephrine reuptake inhibitor for attention-deficit hyperactivity disorder, may lead to severe complications, notably cardiac issues, upon overdose. We present a unique case of venoarterial extracorporeal membrane oxygenation (VA-ECMO) rescue for atomoxetine-induced cardiogenic shock.
UNASSIGNED: We report a 30-year-old man who, after ingesting a significant overdose of atomoxetine, experienced seizures and severe cardiogenic shock, necessitating VA-ECMO for resuscitation. While prior reports have noted cardiovascular complications like QTc prolongation and Takotsubo cardiomyopathy following atomoxetine overdose, this case is notable for its life-threatening circulatory failure, which required ECMO intervention. Swift recognition coupled with VA-ECMO initiation, endoscopic medication removal, intravenous lipid emulsion, and activated charcoal may have played a pivotal role in stabilizing the patient and facilitating recovery.
UNASSIGNED: Healthcare practitioners should recognize the severe cardiac complications of atomoxetine overdose. Careful monitoring with ECG and echocardiography, along with providing intensive care, is crucial in managing critical cases.

As the medical complexity of pregnant patients increases, the rate of maternal morbidity has risen. Maternal cardiovascular disease is a leading cause of maternal morbidity and mortality followed closely by sepsis and infection, both of which may be associated with respiratory failure. There has been an expansion in the application of extracorporeal life support in pregnant and peripartum patients which requires obstetric anesthesiologists to understand the indications, obstetric and medical considerations, relative advantages and potential complications of this invasive technology in this population. Obstetricians and anesthesiologists who care for women on the labor floor must strive to recognize at-risk and deteriorating patients, facilitate escalation of care when appropriate, and engage consultant teams to consider the need for extracorporeal support in high-risk circumstances. This article reviews the epidemiology, indications, specific considerations, potential complications, and outcomes of extracorporeal life support in pregnant and peripartum patients.

Heart failure continues to pose a significant burden in terms of morbidity, mortality, and healthcare costs worldwide despite the implementation of guideline-directed medical therapy. Addressing this challenge and improving clinical outcomes for this patient population remains an urgent priority. Recognizing the limitations in current medical approaches and exploring strategies to overcome these limitations are crucial steps toward improving future outcomes. Various device-based interventions, such as Cardiac Resynchronization Therapy devices and Left Ventricular Assist Devices, have demonstrated notable benefits for individuals with heart failure. Our review is aimed at summarizing the ongoing research into new device therapies for heart failure, emphasizing their potential to overcome the current challenges in treatment. By utilizing Clinicaltrials.gov, an online repository, we conducted a comprehensive search for trials investigating emerging device therapies for patients dealing with heart failure.

UNASSIGNED: Furosemide (FSM), a potent loop diuretic, is used to treat edema due to hypertension, congestive heart failure, and liver and renal failures. FSM applications are limited by its low bioavailability. Our aim is to use different nanoencapsulation strategies to control the release of FSM and enhance its pharmacokinetic properties.
UNASSIGNED: Two types of FSM-loaded nanocapsules, namely FSM-loaded lipid nanocapsules (LNCs) and polymeric nanocapsules (PNCs), were developed, physicochemically characterized, and subjected to pharmacokinetic and pharmacodynamic studies. Lipid nanocapsules were prepared by the simple phase inversion method using LabrafacTM lipid, while the polymeric nanocapsules were prepared by nanoprecipitation method using polycaprolactone polymer.
UNASSIGNED: Transmission electron microscopy ascertains spherical structures, corroborating the nanometric diameter of both types of nanocapsules. The particle size of the optimized FSM-loaded LNCs and FSM-loaded PNCs was 32.19 ± 0.72 nm and 230.7 ± 5.13 nm, respectively. The percent entrapment efficiency was 63.56 ± 1.40% of FSM for the optimized PNCs. The in vitro release study indicated prolonged drug release compared to drug solutions. The two loaded nanocapsules systems succeeded in enhancing the pharmacokinetic parameters in comparison to the marketed FSM solution with superior diuretic activity (p < 0.05). The results of the stability study and the terminal sterilization by autoclave indicated the superiority of LNCs over PNCs in maintaining the physical parameters under storage conditions and the drastic conditions of sterilization.
UNASSIGNED: LNCs and PNCs are considered promising nanosysems for improving the diuretic effect of FSM.

The coronavirus disease 2019 (COVID-19) pandemic was a cataclysmic event that infected over 772 million and killed over 6.9 million people worldwide. The pandemic pushed hospitals and society to their limits and resulted in incredibly severe respiratory disease in millions of people. This severe respiratory disease often necessitated maximum medical therapy, including the use of extracorporeal membrane oxygenation. While our understanding of COVID-19 and its treatment continue to evolve, we review the current evidence to guide the care of patients with severe COVID-19 infection.

A large body of evidence indicates that vasopressin (AVP) and steroid hormones are frequently secreted together and closely cooperate in the regulation of blood pressure, metabolism, water-electrolyte balance, and behavior, thereby securing survival and the comfort of life. Vasopressin cooperates with hormones of the hypothalamo-pituitary-adrenal axis (HPA) at several levels through regulation of the release of corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), and multiple steroid hormones, as well as through interactions with steroids in the target organs. These interactions are facilitated by positive and negative feedback between specific components of the HPA. Altogether, AVP and the HPA cooperate closely as a coordinated functional AVP-HPA system. It has been shown that cooperation between AVP and steroid hormones may be affected by cellular stress combined with hypoxia, and by metabolic, cardiovascular, and respiratory disorders; neurogenic stress; and inflammation. Growing evidence indicates that central and peripheral interactions between AVP and steroid hormones are reprogrammed in cardiovascular and metabolic diseases and that these rearrangements exert either beneficial or harmful effects. The present review highlights specific mechanisms of the interactions between AVP and steroids at cellular and systemic levels and analyses the consequences of the inappropriate cooperation of various components of the AVP-HPA system for the pathogenesis of cardiovascular and metabolic diseases.

Background. Data on the prevalence of cardiac failure with preserved ejection in the haemodialysis population, which impacts treatment strategy, mortality, and morbidity, are scarce. Aims and Objectives. Estimate the prevalence of heart failure with preserved ejection fraction (HFpEF) in haemodialysis patients Classify cardiac failure and ascertain the risk factors influencing HFpEF in haemodialysis patients. Methods. All consenting individuals on haemodialysis over 18 years of age were included. Lung ultrasound was performed as per the LUST study protocol, and the labs were documented. Echocardiographic parameters were measured using two-dimensional (2D ECHO). Results. A total of 102 patients consented to participate in the study, which included 63 males (61.8%) and 39 females (38.2%). The mean patient age was 53 ± 13.1 years. The dialysis vintage of the participants was 38.92 ± 6.947 months. 47 (46.1%) patients had diabetes and 88 (80.4%) had hypertension. ECG findings included sinus rhythm (51/102, 50%), sinus tachycardia (22/102, 21.6%), ST-T wave abnormalities (18/102, 17.6%), and atrial fibrillation (11/102, 10.8%). Heart failure with preserved ejection fraction (HFpEF) was present in 44/102 (43.14%), heart failure with mid-range EF in 14/102 (13.72%), and heart failure with reduced EF in 13/102 (12.7%) patients. The ejection fraction was positively associated with haemoglobin (r = 0.23; p = 0.044), and calcium levels (r = 0.25; p =0 .03). E/lateral e\' ratio was positively correlated with NT pro-BNP (r = 0.63; p < 0.001), systolic blood pressure (r = 0.44; p = 0.003) and age (r = 0.353; p = 0.003) and negatively correlated with transferrin saturation (r = -0.353; p = 0.027) and diastolic blood pressure (r = -0.31; p = 0.040). Binary logistic regression analysis revealed that the odds of diastolic dysfunction increased by 2.3 times with each unit increase of creatinine, and diabetics have 7.66 times higher risk for diastolic dysfunction. Binary logistic regression involving ejection fraction (EF) and all laboratory and clinical parameters revealed odds of HFpEF increased by 1.93 times with each unit increase in age, odds of HFpEF increases by 1.53 times with each unit increase in phosphorous and odds of HFpEF increased by 1.1 times with a unit increase of systolic blood pressure. Conclusion. HFpEF is the predominant form of heart failure in haemodialysis patients. Haemoglobin and calcium were positively associated with ejection fraction. Advancing age, elevated creatinine and diabetes mellitus levels are independent predictors of diastolic dysfunction in haemodialysis patients.

BACKGROUND: Pump-controlled retrograde trial off (PCRTO) is described as an effective weaning strategy for veno-arterial extracorporeal membrane oxygenation (ECMO) in the guidelines. Contrastingly, there is no established weaning strategy for veno-arteriovenous (V-AV) ECMO. We report a novel application of PCRTO in a patient undergoing V-AV ECMO.
METHODS: A 49-year-old man had pneumonia and a history of kidney transplantation. Two days after intubation, respiratory failure progressed and veno-venous (V-V) ECMO was introduced. On day 7 after ECMO, the configuration was changed to V-AV ECMO owing to septic cardiomyopathy due to suspected cholangitis. On day 15, with partial haemodynamic improvement and persistent respiratory failure, PCRTO was performed; the patient was safely returned to V-V ECMO.
CONCLUSIONS: In patients undergoing V-AV ECMO, PCRTO could have the potential to accurately simulate decannulation of the arterial cannula.
CONCLUSIONS: This novel weaning strategy could be considered in patients undergoing V-AV ECMO.

UNASSIGNED: Victoria, Australia provides a centralised state ECMO service, supported by ambulance retrieval. Equity of access to this service has not been previously described.
UNASSIGNED: Describe the characteristics of ECMO recipients and quantify geographical and socioeconomic influence on access.
UNASSIGNED: Retrospective observational study with spatial mapping.
UNASSIGNED: Adult (≥18 years) ECMO recipients from July 2016-June 2022. Data from administrative Victorian Admissions Episodes Database analysed in conjunction with Australian Urban Research Infrastructure Network population data and choropleth mapping. Presumed ECMO modes were inferred from cardiopulmonary bypass and pre-hospital cardiac arrest codes. Spatial autoregressive models including Moran\'s test used for spatial lag testing.
UNASSIGNED: Demographics and outcomes of ECMO recipients; ECMO incidence by patient residence (Statistical-Area Level 2, SA-2) and Index of Relative Socioeconomic Advantage and Disadvantage (IRSAD); and ECMO utilisation adjusted for patient factors and linear distance from the central ECMO referral site.
UNASSIGNED: 631 adults received ECMO over 6 years, after exclusion of paediatric (n = 242), duplicate (n = 135), and interstate or incomplete (n = 72) records. Mean age was 51.8 years, and 68.8 % were male. Overall ECMO incidence was 3.00 ± 3.95 per 105 population. 135 (21.4 %) were presumed VA-ECMO, 59 (9.3 %) presumed ECPR, and 437 (69.3 %) presumed VV-ECMO. Spatial lag was non-significant after adjusting for patient characteristics. Distance from the central referral site (dy/dx = 0.19, 95% CI -0.41-0.04, p = 0.105) and IRSAD score (dy/dx = 0.17, 95% CI -0.19-0.53, p = 0.359) did not predict ECMO utilisation.
UNASSIGNED: Victorian ECMO incidence rates were low. We did not find evidence of inequity of access to ECMO irrespective of regional area or socioeconomic status.