Transcriptional control of cardiac energy metabolism in health and disease: Lessons from animal models.

Cardiac ATP production is tightly regulated in order to satisfy the evolving energetic requirements imposed by different cues during health and pathological conditions. In order to sustain high ATP production rates, cardiac cells are endowed with a vast mitochondrial network that is essentially acquired during the perinatal period. Nevertheless, adult cardiac cells also adapt their mitochondrial mass and oxidative function to changes in energy demand and substrate availability by fine-tuning the pathways and mitochondrial machinery involved in energy production. The reliance of cardiac cells on mitochondrial metabolism makes them particularly sensitive to alterations in proper mitochondrial function, so that deficiency in energy production underlies or precipitates the development of heart diseases. Mitochondrial biogenesis is a complex process fundamentally controlled at the transcriptional level by a network of transcription factors and co-regulators, sometimes with partially redundant functions, that ensure adequate energy supply to the working heart. Novel uncovered regulators, such as RIP140, PERM1, MED1 or BRD4 have been recently shown to modulate or facilitate the transcriptional activity of the PGC-1s/ERRs/PPARs regulatory axis, allowing cardiomyocytes to adapt to a variety of physiological or pathological situations requiring different energy provision. In this review, we summarize the current knowledge on the mechanisms that regulate cardiac mitochondrial biogenesis, highlighting the recent discoveries of new transcriptional regulators and describing the experimental models that have provided solid evidence of the relevant contribution of these factors to cardiac function in health and disease.

Is Reiki effective in reducing heart rhythm, cortisol and anxiety and improving biochemical parameters in individuals with cardiac disesase? Randomized placebo-controlled trial.

AIMS: The aim of this study was to examine the effect of Reiki in patients with cardiac disease. METHODS AND RESULTS: This study was a single-blind, pre-post-test, randomized, placebo-controlled study. Patients from the cardiology outpatient clinic of a training and research hospital were randomized into three groups: Reiki (n = 22), sham (placebo) (n = 21), and control (no treatment) (n = 22). Data were collected using a personal information form, biochemical parameters, cortisol levels, Beck Anxiety Inventory, and electrocardiography analysis. The Reiki group received Reiki to nine main points for 30 min, while the sham Reiki group received the same points during the same period without starting energy flow. On day two, performed Distance Reiki for 30 minutes. After one week, the researchers administered the Beck Anxiety Inventory, assessed the biochemical parameters and cortisol levels, and analyzed the electrocardiography again. Of the patients, 52.3% were male and 47.7% were female, and the mean age (years) is 60.45 ± 9.67 years. The control group had a significantly higher posttest cortisol level than the other groups (p = 0.002). According to the post-hoc analysis, there was a significant difference between the Reiki versus control groups and sham versus control groups (p = 0.002). The control group had a significantly higher post-test cortisol level than the pre-test cortisol level (p = 0.008). Reiki group had a significantly lower mean posttest Beck Anxiety Inventory score than the other groups (p < 0.001). There was no difference between the electrocardiography results of the groups (p > 0.05). CONCLUSION: Reiki reduces blood cortisol levels and anxiety levels in patient with cardiac diseases.

Psychological interventions targeting mental health and stress among females with cardiac disease: a scoping review.

Interventions that target mental health symptoms and stress among those with established cardiac disease have included predominately male samples despite female patients reporting greater severity of these symptoms. The aim of this scoping review was to synthesize the published literature on psychological interventions for females with cardiac disease. We conducted a systematic search of peer-reviewed randomized clinical trials (RCTs) published in the English language from 2003 to 2023, in three databases: Medline (Ovid), PsycInfo (Ovid), and CINAHL (EBSCO). Articles that included female samples, a control or comparison group, implemented psychological interventions, and measured depression, anxiety, or stress as an outcome were included in the review. Nine articles describing eight RCTs of psychological interventions, with a total of 1587 female patients with cardiac disease, were included. Interventions were most successful at reducing stress (75% of studies measuring stress reported efficacy), while symptoms of depression and anxiety were less responsive to intervention (∼30% of studies targeting these symptoms reported improvements) in comparison to a control condition. This scoping review highlights that further advancement in knowledge is required to better address the needs of females with cardiac disease and distress, particularly depression and anxiety.

Orchestrating Resilience: How Neuropilin-2 and Macrophages Contribute to Cardiothoracic Disease.

Immunity has evolved to balance the destructive nature of inflammation with wound healing to overcome trauma, infection, environmental insults, and rogue malignant cells. The inflammatory response is marked by overlapping phases of initiation, resolution, and post-resolution remodeling. However, the disruption of these events can lead to prolonged tissue damage and organ dysfunction, resulting long-term disease states. Macrophages are the archetypic phagocytes present within all tissues and are important contributors to these processes. Pleiotropic and highly plastic in their responses, macrophages support tissue homeostasis, repair, and regeneration, all while balancing immunologic self-tolerance with the clearance of noxious stimuli, pathogens, and malignant threats. Neuropilin-2 (Nrp2), a promiscuous co-receptor for growth factors, semaphorins, and integrins, has increasingly been recognized for its unique role in tissue homeostasis and immune regulation. Notably, recent studies have begun to elucidate the role of Nrp2 in both non-hematopoietic cells and macrophages with cardiothoracic disease. Herein, we describe the unique role of Nrp2 in diseases of the heart and lung, with an emphasis on Nrp2 in macrophages, and explore the potential to target Nrp2 as a therapeutic intervention.

Surface plasmon resonance biosensors for early troponin detection.

Acute myocardial infarction (AMI) is one of the life-threatening causes that decrease blood flow to the heart, leading to increased mortality and related complications. Recently, the measure of blood concentration of cardiac biomarkers has been suggested to overcome the limitations of electrocardiography (ECG) analyses for early diagnosis of this disease. Troponins, especially cardiac troponin I and cardiac troponin T, with high sensitivity and specificity, are considered the gold standards in myocardial diagnosis. Recently, the use of new biosensors such as surface plasmon resonance (SPR) for early detection of these biomarkers has been greatly appreciated. Due to the rapid, sensitive, real-time, and label-free detection of SPR-based biosensors, they can be applied for selective and nonspecific absorption that is intended to be used as an in situ cardiac biosensor. Here, we exclusively discussed the updated developments of these valuable predictors for the possible occurrence of AMI detected by SPR.

Decentralization and Integration of Advanced Cardiac Care for the World's Poorest Billion Through the PEN-Plus Strategy for Severe Chronic Non-Communicable Disease.

Rheumatic and congenital heart disease, cardiomyopathies, and hypertensive heart disease are major causes of suffering and death in low- and lower middle-income countries (LLMICs), where the world's poorest billion people reside. Advanced cardiac care in these counties is still predominantly provided by specialists at urban tertiary centers, and is largely inaccessible to the rural poor. This situation is due to critical shortages in diagnostics, medications, and trained healthcare workers. The Package of Essential NCD Interventions - Plus (PEN-Plus) is an integrated care model for severe chronic noncommunicable diseases (NCDs) that aims to decentralize services and increase access. PEN-Plus strategies are being initiated by a growing number of LLMICs. We describe how PEN-Plus addresses the need for advanced cardiac care and discuss how a global group of cardiac organizations are working through the PEN-Plus Cardiac expert group to promote a shared operational strategy for management of severe cardiac disease in high-poverty settings.

Post-surgery survival and associated factors for cardiac patients in Ethiopia: applications of machine learning, semi-parametric and parametric modelling.

INTRODUCTION: Living in poverty, especially in low-income countries, are more affected by cardiovascular disease. Unlike the developed countries, it remains a significant cause of preventable heart disease in the Sub-Saharan region, including Ethiopia. According to the Ethiopian Ministry of Health statement, around 40,000 cardiac patients have been waiting for surgery in Ethiopia since September 2020. There is insufficient information about long-term cardiac patients' post-survival after cardiac surgery in Ethiopia. Therefore, the main objective of the current study was to determine the long-term post-cardiac surgery patients' survival status in Ethiopia. METHODS: All patients attended from 2012 to 2023 throughout the country were included in the current study. The total number of participants was 1520 heart disease patients. The data collection procedure was conducted from February 2022- January 2023. Machine learning algorithms were applied. Gompertz regression was used also for the multivariable analysis report. RESULTS: From possible machine learning models, random survival forest were preferred. It emphasizes, the most important variable for clinical prediction was SPO2, Age, time to surgery waiting time, and creatinine value and it accounts, 42.55%, 25.17%,11.82%, and 12.19% respectively. From the Gompertz regression, lower saturated oxygen, higher age, lower ejection fraction, short period of cardiac center stays after surgery, prolonged waiting time to surgery, and creating value were statistically significant predictors of death outcome for post-cardiac surgery patients' survival in Ethiopia. CONCLUSION: Some of the risk factors for the death of post-cardiac surgery patients are identified in the current investigation. Particular attention should be given to patients with prolonged waiting times and aged patients. Since there were only two fully active cardiac centers in Ethiopia it is far from an adequate number of centers for more than 120 million population, therefore, the study highly recommended to increase the number of cardiac centers that serve as cardiac surgery in Ethiopia.

Obstetrical and neonatal outcomes in patients with surgically repaired heart disease.

BACKGROUND: Congenital and acquired heart disease complicate 1% to 4% of pregnancies in the United States. Beyond the risks of the underlying maternal congenital heart disease, cardiac surgery and its sequelae, such as surgical scarring resulting in higher rates of arrhythmias and implanted valves altering anticoagulation status, have potential implications that could affect gestation and delivery. OBJECTIVE: This study aimed to investigate whether history of maternal cardiac surgery is associated with adverse obstetrical or neonatal outcomes compared with patients without a history of cardiac disease or surgery, considered "healthy controls." STUDY DESIGN: This is a secondary analysis of retrospective cohort studies performed at a tertiary care facility in the United States comparing obstetrical outcomes in patients with a history of open cardiac surgery who delivered from January 2007 to December 2018 with healthy controls, who delivered from April 2020 to July 2020. There were 74 pregnancies in 61 patients with a history of open cardiac surgery that were compared with pregnancies in healthy controls. Of the 74 pregnancies, 65 were successfully matched based on gestational age to controls at a 1:3 (case-to-control) ratio. The remainder of cases were matched at a 1:2 or 1:1 ratio; therefore, a total of 219 control pregnancies were included in the analysis. Our primary outcome was the incidence of hypertensive disorders of pregnancy, as well as cesarean delivery, in patients with a history of open cardiac surgery compared with healthy controls. Our secondary outcome was the incidence of low-birthweight neonates in patients with a history of open cardiac surgery compared with healthy controls. RESULTS: Patients with a history of cardiac surgery were not more likely to have any hypertensive disorder diagnosed than healthy controls. Patients with a history of cardiac surgery were more likely to have an operative delivery (P<.0001) but equally likely to have a cesarean delivery (P=.528) compared with healthy controls. Birthweight was not statistically different of 2655±808 g in neonates born to patients with a history of cardiac surgery vs 2844±830 g born to healthy controls (P=.092). CONCLUSION: Patients with a history of cardiac surgery may not be at higher risk of hypertensive disorder diagnosis during pregnancy. Similarly, most patients with a history of cardiac surgery are also likely not at higher risk of cesarean delivery or low-birthweight neonates.

Breastfeeding Practices in Patients with Heart Disease Stratified by Area Deprivation Index.

Objective: We sought to evaluate breastfeeding (BF) practices in patients with maternal cardiac disease (MCD) stratified by area deprivation index (ADI) to identity communities at risk. Study Design: Retrospective cohort of patients managed by the University of Alabama at Birmingham (UAB) Cardio-Obstetrics Program. Patients were included if they had ≥1 prenatal visit with the Cardio-Obstetrics team, delivered at UAB, and had a street address on file. The primary outcome was BF rate at hospital discharge. Secondary outcomes included BF intent on admission and BF at the postpartum (PP) visit. ADI reports socioeconomic disadvantage at the census tract level; 1 = least deprived and 100 = most deprived. Baseline characteristics and BF rates were compared by ADI categories: Low (ADI 1-33), medium (ADI 34-66), and high (ADI 67-100). Results: One hundred and forty-eight patients were included: 14 (10%) low, 42 (28%) medium, and 92 (62%) high ADI. Patients in the high ADI category were younger relative to those in the medium or low ADI (26 versus 28 versus 32 years; p < 0.01) and less likely to be married or living with a partner (30.4% versus 58.5% versus 71.4%; p < 0.01), There was no difference in BF intent between the lowest, medium, and highest ADI categories (85.7% versus 85.4% versus 81.6%; p = 0.38) or BF rates at hospital discharge (100% versus 92.7% versus 85.6%, p = 0.23). However, there was a significant difference in BF rates at the PP visit (90% versus 63.0% versus 38.6%; p < 0.01) even after controlling for differences in baseline characteristics (odds ratio = 0.11 (95% confidence interval [0.01-0.93]), p = 0.043). Conclusions: There was an association between living in a resource-poor community and early cessation of BF in our population of patients with MCD. Community-based interventions targeting mothers with heart disease living in high ADI communities may help these individuals achieve higher BF rates.

Myxomatous mitral valve disease and associated pulmonary hypertension might increase serum angiopoietin-2 in dogs.

OBJECTIVE: To evaluate the relationships between the severity of myxomatous mitral valve disease (MMVD) and pulmonary hypertension (PH) and serum angiopoietin (Ang)-1 and Ang-2 concentrations in dogs with MMVD. ANIMALS: 74 dogs (control, n = 12; MMVD, n = 62) were included. METHODS: Serum Ang-1 and Ang-2 concentrations were estimated using the canine-specific ELISA kit. The concentrations were compared between dogs with MMVD and healthy dogs, and they were analyzed according to the severity of MMVD and PH. RESULTS: The median serum Ang-1 concentration did not differ among the study groups. The median serum Ang-2 concentration was higher in dogs with stage B2 MMVD (P = .041) and acute congestive heart failure (P = .002) than in control dogs. In addition, the median serum Ang-2 concentration was higher in MMVD dogs with PH than in those without PH (P = .031). Serum Ang-2 concentration was correlated with vertebral heart score (rs = 0.36, P = .004) and vertebral left atrial score (r = 0.50, P < .001) in dogs with MMVD, and correlated with vertebral heart score (r = 0.63, P = .01), maximum E wave amplitude of the diastolic transmitral flow (rs = 0.61, P = .018), ejection fraction (rs = -0.77, P < .001) and fractional shortening (rs = -0.56, P = .032) in dogs with acute congestive heart failure. CLINICAL RELEVANCE: Circulating Ang-2 levels increase in dogs with the severity of MMVD and the presence of PH.

Development and implementation of a pregnancy heart team at a Southeastern United States tertiary hospital: a qualitative study.

BACKGROUND: The United States has seen a significant rise in maternal mortality and morbidity associated with cardiovascular disease over the past 4 decades. Contributing factors may include an increasing number of parturients with comorbid conditions, a higher rate of pregnancy among women of advanced maternal age, and more patients with congenital heart disease who survive into childbearing age and experiencing pregnancy. In response, national medical organizations have recommended the creation of multidisciplinary obstetric-cardiac teams, also known as pregnancy heart teams, to provide comprehensive preconception counseling and coordinated pregnancy management that extend through the postpartum period. OBJECTIVE: We sought to describe the development and implementation of a pregnancy heart team for parturients with cardiac disease at a southeastern United States tertiary hospital. STUDY DESIGN: This was a qualitative study that was conducted among healthcare team members involved during the pregnancy heart team formation. Semi-structured interviews were conducted between April and May 2022, professionally transcribed, and the responses were thematically coded for categories and themes using constructs from The Consolidated Framework for Implementation Research. RESULTS: Themes identified included intentional collaboration to improve outpatient and inpatient coordination through earlier awareness of patients who meet the criteria and via documented care planning. The pregnancy heart team united clinicians around best practices and coordination to promote the success and safety of pregnancies and not only to minimize maternal health risks. Developing longitudinal care plans was critical among the pathway team to build on collective expertise and to provide clarity for those on shift to reduce hesitancy and achieve timely, vetted practices without additional consults. Establishing a proactive approach of specialists offering their perspectives was viewed as positively contributing to a culture of speaking up. Barriers to the successful development and sustainability of the pregnancy heart team included unmet administrative needs and clinician turnover within a context of shortages in staffing and high workload. CONCLUSION: This study described the process of developing and implementing a pregnancy heart team at 1 institution, thereby offering insights for future multidisciplinary care for maternal cardiac patients. Establishing pregnancy heart teams can enhance quality care for high-risk patients, foster learning and collaboration among physician and nursing specialties, and improve coordination to manage complex maternal cardiac cases.

Perioperative sildenafil therapy in pulmonary hypertension associated with congenital cardiac disease: An updated meta-analysis.

To provide an updated meta-analysis to evaluate the efficacy and safety of sildenafil on pediatric patients with pulmonary hypertension (PH) associated with congenital heart disease (CHD). To assess the efficacy and safety of sildenafil, five outcomes, time duration of post-operative need for mechanical ventilation, time duration of post-operative ICU stay, length of hospitalization (LOH), the incidence of mortalities and pulmonary arterial pressure to aortic pressure ratio (PAP/AoP) were regarded as primary efficacy outcomes. Standardized mean difference (SMD) was calculated for continuous data. In comparison to the control group (CG), there was a significant decrease in the time duration of ICU stay in the sildenafil group (SG) (SMD = -0.61 [95% CI -1.17, 0.04]; P < 0.01, I2 = 85%). Length of hospitalization was assessed in the sildenafil and control groups (SMD = -0.18 [95% CI -0.67, 0.31] P = 0.05, I2 = 62%). However, there was no significant difference seen in mortality rates between the SG and CG (SMD = 0.53 [ 95% CI 0.13, 2.17] p = 0.61, I2 = 0%), in the time duration of postoperative mechanical ventilation between the SG and CG (SMD = -0.23 [95% CI -0.49, 0.03] p = 0.29, I2 = 19%), or PAP/AoP ratio between the SG and CG (SMD = -0.42 [95% CI -1.35, 0.51] P < 0.01, I2 = 90%). Based on our analysis, sildenafil has little to no effect in reducing postoperative morbidity and mortality due to PH in infants and children with CHD.

The role of deubiquitinases in cardiac disease.

Deubiquitinases are a group of proteins that identify and digest monoubiquitin chains or polyubiquitin chains attached to substrate proteins, preventing the substrate protein from being degraded by the ubiquitin-proteasome system. Deubiquitinases regulate cellular autophagy, metabolism and oxidative stress by acting on different substrate proteins. Recent studies have revealed that deubiquitinases act as a critical regulator in various cardiac diseases, and control the onset and progression of cardiac disease through a board range of mechanism. This review summarizes the function of different deubiquitinases in cardiac disease, including cardiac hypertrophy, myocardial infarction and diabetes mellitus-related cardiac disease. Besides, this review briefly recapitulates the role of deubiquitinases modulators in cardiac disease, providing the potential therapeutic targets in the future.

Mitochondrial Dysfunction in Heart Failure: From Pathophysiological Mechanisms to Therapeutic Opportunities.

Mitochondrial dysfunction, a feature of heart failure, leads to a progressive decline in bioenergetic reserve capacity, consisting in a shift of energy production from mitochondrial fatty acid oxidation to glycolytic pathways. This adaptive process of cardiomyocytes does not represent an effective strategy to increase the energy supply and to restore the energy homeostasis in heart failure, thus contributing to a vicious circle and to disease progression. The increased oxidative stress causes cardiomyocyte apoptosis, dysregulation of calcium homeostasis, damage of proteins and lipids, leakage of mitochondrial DNA, and inflammatory responses, finally stimulating different signaling pathways which lead to cardiac remodeling and failure. Furthermore, the parallel neurohormonal dysregulation with angiotensin II, endothelin-1, and sympatho-adrenergic overactivation, which occurs in heart failure, stimulates ventricular cardiomyocyte hypertrophy and aggravates the cellular damage. In this review, we will discuss the pathophysiological mechanisms related to mitochondrial dysfunction, which are mainly dependent on increased oxidative stress and perturbation of the dynamics of membrane potential and are associated with heart failure development and progression. We will also provide an overview of the potential implication of mitochondria as an attractive therapeutic target in the management and recovery process in heart failure.

So close, yet so far away: the relationship between MAM and cardiac disease.

Mitochondria-associated membrane (MAM) serve as crucial contact sites between mitochondria and the endoplasmic reticulum (ER). Recent research has highlighted the significance of MAM, which serve as a platform for various protein molecules, in processes such as calcium signaling, ATP production, mitochondrial structure and function, and autophagy. Cardiac diseases caused by any reason can lead to changes in myocardial structure and function, significantly impacting human health. Notably, MAM exhibits various regulatory effects to maintain cellular balance in several cardiac diseases conditions, such as obesity, diabetes mellitus, and cardiotoxicity. MAM proteins independently or interact with their counterparts, forming essential tethers between the ER and mitochondria in cardiomyocytes. This review provides an overview of key MAM regulators, detailing their structure and functions. Additionally, it explores the connection between MAM and various cardiac injuries, suggesting that precise genetic, pharmacological, and physical regulation of MAM may be a promising strategy for preventing and treating heart failure.

Pregnancy reference intervals and exertion and breathlessness ratings for the six minute walk test in healthy nulliparous people.

Background: The Six Minute Walk Test (6MWT) is a simple, non-invasive, well-validated test that assesses cardiorespiratory fitness however is rarely used in pregnant people. It may have clinical utilization to assess fitness, breathing and exertion in pregnancy however no reference intervals exist for people 14+0 to 35+6 weeks gestation. We determined the reference intervals for distance walked for the 6MWT, including exertional and breathlessness ratings for this group. Method: We conducted a prospective observational cohort study of 196 healthy nulliparous pregnant people in earlier pregnancy (EP) 14+0 to 23+6 weeks, and middle pregnancy (MP) 24+0 to 35+6 gestation, who performed a standardized 6MWT protocol including rating exertion and breathlessness (Rating Perceived Exertion (RPE) scale (1 none -15 maximal) and Modified Borg Dyspnea (MBD) scale (0 none - 10 maximal)). Results: The mean ± SD distance walked was 548 ± 80.9 (EP) versus 547 ± 87.3 (MP) meters (m) P = 0.928. 6MWT reference intervals for the distance walked for the 6MWT were 392-704 m (EP) and 376-718 m (MP). Median (IQR) exertion and breathlessness ratings with exercise for the EP and MP group were 6 (4,7) and 0.5 (0,1) and 6 (4,8) and 0.5 (0,1) respectively. There were no adverse events. Conclusion: The 6MWT is safe, feasible and acceptable in pregnant people. The reference intervals for the 6MWT are 392-704 m in people 14+0 to 23+6 weeks gestation and 376-718 m for people 24+0 to 35+6 weeks gestation. Exertion was light and breathlessness was just noticeable with the 6MWT.

Feasibility and Safety of Concomitant Laparoscopic Cholecystectomy With Open-Heart Surgery: A Systematic Review and Our Early Clinical Experience.

Significant valvular or coronary artery disease may co-exist in patients presenting with symptomatic cholelithiasis. Isolated laparoscopic cholecystectomy in these cases is often associated with cardiac complications. Addressing the cardiac condition first may result in flaring up of cholecystitis during postoperative recovery and is associated with adverse outcomes. Open-heart surgery followed by laparoscopic cholecystectomy during a single operative setting is an option in these situations. The aim of our study is to review the published articles for this strategy and to share our initial experience with two such patients. PubMed, OVID Medline, and Cochrane library database were used, and we searched these databases using Medical Subject Headings (MeSH) terms and keywords from the inception date until August 1, 2023, and did not restrict our search to any language, study type, sample size, or publication date. All the publications reporting concomitant laparoscopic cholecystectomy and open-heart surgery were identified and a systematic review was carried out. Our first case underwent coronary artery bypass grafting and laparoscopic cholecystectomy. The second patient underwent a double valve replacement and laparoscopic cholecystectomy. Both the patients made an uneventful recovery, and are alive and doing well. Concomitant open-heart surgery and laparoscopic cholecystectomy in certain situations may be necessary and can be performed safely.

Erratum: The impact of COVID-19 on pulmonary, neurological, and cardiac outcomes: evidence from a Mendelian randomization study.

[This corrects the article DOI: 10.3389/fpubh.2023.1303183.].