Congestive Heart Failure

Background and Rationale Spinal anesthesia-induced hypotension is the most common hemodynamic complication in obstetric anesthesia, with reported incidence rates ranging from 50% to 80% in parturients undergoing elective cesarean section. The underlying pathophysiology involves sympathetic blockade-mediated arteriolar and venous vasodilation, resulting in decreased systemic vascular resistance and reduced venous return, further compounded by aortocaval compression exerted by the gravid uterus. Current prophylactic strategies including left uterine displacement, fluid co-loading, and vasopressor infusion remain the standard of care. However, these pharmacological approaches may be associated with tachycardia, hypertension, and inter-individual response variability, underscoring the need for complementary non-pharmacological interventions. Preoperative anxiety exerts measurable effects on autonomic nervous system balance, potentially amplifying sympathetic tone and increasing hemodynamic instability following neuraxial blockade. Slow, controlled breathing exercises have been shown to enhance baroreflex sensitivity and augment parasympathetic vagal activity, suggesting that a brief mindfulness-based breathing intervention may attenuate sympathetic hyperactivity through an "autonomic preconditioning" mechanism. Randomization and Allocation Concealment Participants will be randomized in a 1:1 ratio using a computer-generated random number sequence. Allocation concealment will be ensured through sequentially numbered, opaque, sealed envelopes (SNOSE), opened only after the patient has been transferred to the operating room and immediately before spinal anesthesia induction. Intervention Protocol Participants in the intervention arm will receive a 5-minute guided mindfulness-based breathing exercise prior to spinal anesthesia, consisting of slow diaphragmatic breathing at approximately 6 breaths per minute (4-second nasal inhalation, 6-second oral exhalation). During each exhalation, participants silently repeat: "My body is relaxing as I exhale." Anesthesia Management All participants will receive spinal anesthesia in the sitting position with intrathecal administration of 11.2 mg hyperbaric bupivacaine + 15 mcg fentanyl + 150 mcg morphine. Hypotension will be defined as a decrease in systolic arterial pressure (SAP) exceeding 20% from baseline and treated with norepinephrine or ephedrine. Bradycardia will be defined as heart rate ≤50 bpm and treated with intravenous atropine (1 mg). Statistical Analysis All analyses will be performed using IBM SPSS Statistics (Statistical Package for the Social Sciences) version 20. Normality will be assessed using Shapiro-Wilk and Kolmogorov-Smirnov tests. Between-group comparisons will be performed using independent samples t-test or Mann-Whitney U test as appropriate. Categorical variables will be compared using chi-square test. Statistical significance will be set at p\<0.05. Sample Size Sample size was calculated using G\*Power 3.1.9.7 software. A clinically meaningful difference of 4.5 mmHg in maximum SAP decrease (effect size = 0.48) was determined to require 70 participants per group at 80% power and 95% confidence level. Accounting for potential dropout, 150 participants (75 per group) will be enrolled.

Background: Almost 3 billion people worldwide, including 89% people in Bangladesh, are exposed to harmful household air pollutants (HAP) emitted from combustion of biomass fuel (wood, agricultural residue, cow dung, etc.) used for cooking. While health risks associated with air-pollution have been reasonably well-studied in developed countries, there is little evidence on health benefits achievable by HAP reduction through clean fuel use such as Liquid Petroleum Gas, especially in low- and middle-income countries (LMICs). Rationale: In the earlier GEOHealth (Round-I) study, the investigators have shown that LPG for 24 months, reduced personal PM2.5 exposure by 58.2 percent which induced novel changes in innate immune and inflammatory responses in women but the changes in chronic cardio-pulmonary markers were not prominent, most likely due to short duration of follow up and probably impact of ambient pollution. Moreover, sustained use of LPG could be challenging as earlier GEOHealth (Round-I) study provided the cook stove and supply of LPG free of cost. A post-completion screening showed \>70% households continued using LPG albeit not exclusively. It is plausible that an intervention using mobile phone-based application can improve the exclusive use of LPG in the communities. Hypothesis: 1. The mobile phone based (mHealth) Behavioural Change Communication (BCC) intervention can be easily incorporated in Government policy that can promote adoption, and increase exclusive use of LPG in the communities. The long-term effect of HAP reduction can be associated with- 2. subclinical measures of cardio-vascular and pulmonary dysfunction. 3. balanced changes in innate/ inflammatory and adaptive immune function (vaccine response). Objectives: To evaluate 1. The effects of a scalable educational intervention (using mHealth application) on adoption and exclusive use of LPG. 2. The long-term effects of HAP reduction on subclinical measures of cardio-vascular and pulmonary dysfunction. 3. The long-term effects of HAP reduction on innate/ inflammatory immune function among women and children and to investigate the influence of HAP exposure on antibody response to vaccines (adaptive immunity). Methods: The investigators will conduct a large household level randomized controlled trial by educational intervention using mobile phone (mHealth) based technology. In addition, the investigators will continue following the cohort and will conduct rigorous and repeated personalized (24 hours) and area-wise (over 5 days) assessments of PM2.5 and black carbon (BC) exposure to examine the long-term effects of HAP reduction on subclinical measures of cardio-pulmonary and immune dysfunction including effect of HAP exposure on antibody response to vaccine. Outcome measures/variables: Personal and surrounding area PM2.5 and BC level will be measured at pre- and post-intervention. Lung function and lung pathology will be assessed through spirometry, Chest X-ray, and High-resolution Computed tomography of the chest (HRCT). Preclinical makers of cardiovascular diseases (CVD) will include blood pressure and EKG. Markers of metabolic dysfunction will be assesses by measuring HbA1c and fasting lipid profile. Immune function will be assessed by phenotyping of Immune cells, functional cytotoxic killer cells, oxidative stress of lymphocytes.

In Ghana, about 88.3 per cent of cardiac admissions are due to Heart failure, making it the leading cause of admission due to heart conditions. Despite improved knowledge on heart failure and an increasing array of evidence-based guideline treatment options, there is still a significant readmission rate worldwide. This may be due to the underutilization of these evidence-based therapies or a lack of proper follow-up on these patients. Recurrent hospital admission is an independent predictor of death in heart failure. Strategies aimed at providing increased support at discharge and effective follow-up may be associated with lower readmission risk. This study aims to assess the effect of extensive post-discharge counselling and effective phone-based follow-up on the 30-day and 90-day heart failure readmission rate at a tertiary hospital in Ghana. This is a single-centre, pilot randomised controlled trial of heart failure patients admitted to the Komfo Anokye Teaching Hospital

There are two chambers in the heart known as ventricles which are responsible for pumping blood to both the lungs and the rest of the body. The right ventricle pumps blood to the lungs for oxygenation. The left ventricle then delivers this oxygenated blood to the organs in the body. When the left ventricle is damaged enough that it is not able to effectively pump blood then it may be necessary to assist it with a mechanical pump. This pump is called left ventricular assist device (LVAD). Left ventricular assist devices (LVADs) improve quality of life and survival in patients with end stage heart failure. However, right ventricular (RV) failure is common in 20-50% of LVAD recipients and is associated with perioperative complications. Traditional two-dimensional ultrasound views of the right ventricle may not accurately depict how well or poorly the right ventricle is working. Three-dimensional (3D) images can overcome the limitations of two-dimensional images and are becoming more commonplace. This goal of this study is to analyze images of the right ventricle taken via 3D transesophageal echocardiography (TEE) during the LVAD implantation to help predict which patients are at higher risk of right ventricular failure within 14 days of the procedure.

Heart failure (HF) is a clinical syndrome with increasing incidence and prevalence, associated with high morbidity, mortality, and economic impact, despite therapeutic advances. Myocardial fibrosis is a common feature across different pathophysiological processes and plays a key role in HF development, with growing research interest specifically in non-ischemic dilated cardiomyopathy (HFrEF phenotype) and hypertrophic cardiomyopathy (HFpEF phenotype). Given its potential reversibility with certain drugs, fibrosis is an attractive therapeutic target, requiring non-invasive methods to monitor fibrogenesis and treatment efficacy. Cardiac magnetic resonance imaging (CMR) is the gold standard for detecting fibrosis but cannot distinguish between active and inactive fibrosis or detect early stages, limitations that may be addressed by gallium-68-labeled fibroblast activation protein inhibitor positron emission tomography/computed tomography (68Ga-FAPI PET/CT). This single-center, prospective, observational pilot study aims primarily to assess myocardial fibrosis in patients with HFrEF (non-ischemic dilated cardiomyopathy) and a subtype of HFpEF (hypertrophic cardiomyopathy) using 68Ga-FAPI PET/CT compared to CMR. Secondary objectives include developing 68Ga-FAPI uptake assessment methodologies for future anti-fibrotic therapy studies and correlating fibrosis with serum cardiac biomarkers and cardiovascular events.

Angiotensin-II (ANG-II) is the end-product of the renin-angiotensin cascade, and acts as a potent endogenous vasoconstrictor through binding to the angiotensin receptor (AT1) on arteriolar vascular smooth muscle. With advancing age, there is a notable decline in plasma renin activity accompanied by decrements in circulating ANG-II and an increase in AT1 receptor density. However, the functional consequence of this age-related adaptation of the renin-angiotensin system (RAS) on the peripheral circulation is not well understood. Likewise, in recent years it has become apparent that cardiovascular disease is a major cause of morbidity in COPD, which may be related to vascular dysfunction and associated adoption of a sedentary lifestyle. In these patients, changes in RAS activity have been linked to peripheral vascular dysfunction, with compelling evidence for improvements in peripheral oxygen use following angiotensin-converting enzyme (ACE) inhibition. Like the aging population, systematic studies evaluating AT1 receptor sensitivity and the efficacy of AT1 receptor blockade on peripheral hemodynamics have not been undertaken. The ubiquitous substance nitric oxide (NO) is now recognized as a key pathway for endothelium-dependent vasodilation, with the bioavailability of NO serving as an indicator for overall vascular health. Cardiac risk factors have been shown to cause impairment in endothelial vasodilator function in both the peripheral and coronary arteries. Coronary vascular dysfunction is an important phase in atherogenesis and is associated with myocardial ischemia. Furthermore, peripheral vascular function has been linked to coronary vascular dysfunction which could have important clinical implications in terms of health screening. Impaired endothelium-dependent vasodilation has been associated with the elderly, patients with COPD, and most cardiovascular diseases including pulmonary hypertension, and heart failure (HF), though the functional consequence of this adaptation on peripheral blood flow regulation remains unclear. Thus, we propose the use of a compound which inhibits the enzyme responsible for NO production in endothelial cells, N-monomethyl-L-arginine (L-NMMA), to temporarily block production of NO and thus determine the importance of this pathway at rest and during physical activity. Additionally, we propose the use of acetylcholine (Ach) to determine endothelial-dependent vasodilation and sodium nitroprusside (SNP) and nitroglycerin (NTG) to determine the endothelial-independent vasodilation in the coronary arteries and the periphery. Oxidative stress associated with aging has been shown to reduce vascular function and antioxidant supplementation restores vascular function to levels that are indistinguishable from healthy young adults. The manner by which this improvement in vascular function occurs is not known by may be acting through a NO dependent mechanism. Histamine has been reported to mediate sustained post-exercise vasodilation through histamine-1 (H1) and histamine-2 (H2) receptor activity, which results in a \~50% elevation in femoral artery blood flow (above resting levels) that lasts for more than 100 minutes after a single bout of moderate-intensity dynamic exercise. Vasodilation can be markedly reduced by giving either fexofenadine (Allegra, a selective H1-receptor antagonist) or ranitidine (Zantac, a selective H2-receptor antagonist). The combination of H1/H2 blockade abolishes \~80% of the post-exercise vasodilation seen after whole-body exercise such as cycling and this observation has been observed in multiple studies in young sedentary, recreationally active, and endurance trained men and women. The impact of histamine on the post-exercise vasodilatory response is substantial; however, the role of H1/H2 receptors in regulating skeletal muscle blood flow during exercise is unknown. Thus, we intend to investigate the role of H1/H2 receptors in the regulation of skeletal muscle blood during exercise as this may be an important pathway in age and disease related reductions in blood flow during exercise. Exercise training and rehabilitation can be used as an alternative approach to combat the deleterious effects oxidative stress on aging and disease. An effective exercise training intervention can decrease sympathetic nervous system activity, improve arterial compliance and vascular endothelial function, and alter the pro- and antioxidant balance resulting in improved endogenous antioxidant defense mechanisms. Moreover, exercise training concomitantly improves musculoskeletal strength and function, glucose regulation and insulin sensitivity, cardiovascular function, body composition, blood chemistry (decreased triglyceride and cholesterol levels), and overall well-being. The physiologic effect of an exercise rehabilitation program in diseases such as COPD, and pulmonary arterial hypertension (PAH) is incompletely understood. However, recent studies suggest that exercise training in this patient population is well tolerated and associated with clinically significant physiologic improvements as well as improvements in various quality of life scores. A unique feature of the proposed studies identified herein is the inclusion of a novel methodological approach to comprehensively evaluate the functional outcome of the proposed pharmacologic interventions. The recent development of a unique combination of nuclear magnetic resonance (NMR) techniques by members of our group enables near-simultaneous measurements of both muscle perfusion and metabolism in vivo. The arterial spin labeling (ASL) technique allows the measurement of both spatially and temporally resolved quantification of perfusion, while the kinetics of phosphocreatine (PCr) depletion and recovery provide high resolution measurements of muscle energetics. The interweaving of these imaging and spectroscopic modules provides the opportunity for determination of skeletal muscle perfusion and metabolism kinetics during and following the stress of physical exercise. Thus, this NMR-based approach, combined with direct measures of muscle fatigue, offers the potential to further define the individual and collective contribution of these variables to the attenuated limb blood flow in the elderly and in patients with COPD and PAH. We propose that each of these pathways outlined above represent an avenue by which vascular function is compromised in the elderly and in patients with COPD, PAH and cardiovascular disease. However, because these pathways are not mutually exclusive, the proposed studies are designed to systematically evaluate hemodynamic responses to intra-arterial or intravenous administration of pharmacologic agents specific for the AT1 receptor (ANG-II and Diovan, AT1 agonist and antagonist, respectively), the Endothelin receptor Type-A (ETA receptor) (BQ-123, ETA antagonist), and the NO pathway (L-NMMA, Ach, and SNP) both before and after exercise training.

The aim of this study is to develop a comprehensive 10-minute protocol based on function and myocardial tissue characterization without the need for contrast injection, which can be standardized for 70% of cardiac patients. To test this 10-minute CMR protocol for its ability to significantly improve diagnostic decision-making and to reduce cost. To test its clinical feasibility, performance and cost-effectiveness in different populations including: Non-ischemic cardiomyopathies (-)OS-CMR and Ischemic Heart Disease and CAD (+)OS-CMR

This is a randomized clinical trial, multicentre, parallel group, open label, to evaluate the use of sodium zirconium cyclosilicate (SZC) to optimize RAASi therapy in patients with heart failure and chronic kidney disease, through up-titration of ACEi, ARB, ARNI or MRA therapy according to clinical guidelines (1), without inducing clinically significant hyperkalemia. Eligible subjects will have been admitted to hospital because of an HF (NYHA I- III) decompensation, will have required intravenous diuretics and will have had mild hyperkalaemic values that needed stabilization or be at risk of developing hyperkalaemia. Subjects will be randomised in a 1:1 ratio to receive SZC or none (standard of care treatment without potassium binders) for 3 months while optimizing RAASi therapies according to the European Society of Cardiology (ESC) guidelines.

Heart failure is a serious manifestation or advanced stage of various heart diseases with high mortality and re-hospitalization rates, and early diagnosis of heart failure is important to improve patient survival. Currently, the prevalence of preclinical heart failure (heart failure stage B) is lacking in China, and the rate of progression of heart failure from stage A/B to symptomatic heart failure (heart failure stage C) and end-stage heart failure (heart failure stage D) and the factors influencing the heart failure development are unknown. The study is an ongoing prospective community-based study. After enrollment, a questionnaire, physical examination, laboratory examination and imaging examination will be administered to each participant at baseline and every 2 years in the follow-up. The laboratory and imaging examination include: blood/urine sample and biochemical measurements, electrocardiogram, echocardiograph, etc. In the follow-up, the incidence of cardiovascular disease, heart failure, other CV events and mortality will be recorded. Whether at baseline or follow-up, if the investigators find that patients are unclear about their disease status, the investigators will notify them by phone and record their subsequent medical behavior and results. In this study, a community-based database and biobank will be established for early screening and long-term prognosis of heart failure in elderly population. Through the analysis of the data, the epidemiological characteristics of early stage of heart failure in elderly population in Shanghai can be identified and a multivariable model predicting heart failure in early stage will be constructed. Furtherly，the investigators will explore the referral criteria and hierarchical management strategies for heart failure through the cooperation between community hospitals and comprehensive hospitals.

This investigator-initiated, pragmatic, registry-based, double-blinded, placebo-controlled, 2x2 factorial, individually randomized trial aims to evaluate the efficacy of daily intake of the nutritional supplements coenzyme Q10 versus placebo, and selenium versus placebo, in preventing heart failure hospitalizations and cardiovascular death in heart failure patients. The trial plans to randomize approximately 4,044 participants in an event-driven design. Participants will be identified through the Danish Administrative Health Registries, which will also serve as the primary source for data collection. Contact with potential participants will be made via the mandatory Danish electronic letter system. No scheduled in-person visits are required in the main study, and all study interventions will be mailed to participants. A substudy involving up to 600 participants will assess the effects of coenzyme Q10 and selenium on functional capacity, treatment compliance, biochemical biomarkers, and cardiac function and structure. This group will attend two in-person visits for additional evaluations, including echocardiography, blood sampling, and a 6-minute walk test at baseline and at the 1-year follow-up.