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Medicina (Kaunas, Lithuania) Jun 2024This study aimed to assess the prevalence, predictors, and outcomes of pulmonary hypertension (PH) in patients with lupus nephritis (LN). Baseline characteristics and...
This study aimed to assess the prevalence, predictors, and outcomes of pulmonary hypertension (PH) in patients with lupus nephritis (LN). Baseline characteristics and clinical outcomes of 387 patients with LN were retrospectively collected from 2007 to 2017. PH was defined as pulmonary artery systolic pressure ≥40 mmHg assessed by resting transthoracic echocardiography. The primary endpoint was all-cause mortality. The secondary endpoint was renal events, defined as the doubling of baseline serum creatinine or end-stage renal disease. Associations between PH and outcomes were analyzed by Cox regression models. A total of 15.3% (59/387) of patients with LN were diagnosed with PH, and the prevalence of PH was higher for patients with an estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m compared to those with an eGFR ≥ 30 mL/min/1.73 m (31.5% vs. 12.6%). Higher mean arterial pressure, lower hemoglobin, and lower triglyceride levels were associated with greater odds of having PH. After adjusting for relevant confounding variables, PH was independently associated with a higher risk for death (HR: 2.01; 95% CI: 1.01-4.00; = 0.047) and renal events (HR: 2.07; 95% CI: 1.04-4.12; = 0.039). PH is an independent risk factor for all-cause mortality and adverse renal outcomes in patients with LN.
Topics: Humans; Female; Male; Hypertension, Pulmonary; Lupus Nephritis; Adult; Retrospective Studies; Prevalence; Middle Aged; Glomerular Filtration Rate; Risk Factors; Proportional Hazards Models
PubMed: 38929605
DOI: 10.3390/medicina60060988 -
Animals : An Open Access Journal From... Jun 2024Ventricular septal defects (VSDs) can lead to congestive heart failure and pulmonary hypertension, particularly in patients with large shunts. However, no surgical...
Ventricular septal defects (VSDs) can lead to congestive heart failure and pulmonary hypertension, particularly in patients with large shunts. However, no surgical treatment for feline VSD has been reported. Here, we elucidated the first surgical correction of an infundibular muscular VSD in a one-year-old Ragdoll cat, atypically located and classified under the Soto classification rather than the standard Kirklin classification, through cardiac arrest using cardiopulmonary bypass-a method rarely used in feline cardiac surgery. Detailed echocardiography revealed that the defect required intervention owing to left heart and main pulmonary artery enlargement. Despite the VSD being located on the contralateral side, as anticipated in the preoperative examinations, the choice of median sternotomy allowed for the successful closure of the defect. Conversely, the insertion of two cannulas into the ascending aorta resulted in damage to the adjacent thoracic duct, causing transient chylothorax, which was resolved with conservative treatment. Cardiac arrest induced by a cardioplegic solution facilitated the surgical procedure, although it leads to anemia in cats. However, on postoperative day 490, the patient exhibited only minor residual shunting, with normalized heart size, and remained healthy. This technique appears to be a viable treatment option for congenital heart disease in cats.
PubMed: 38929355
DOI: 10.3390/ani14121736 -
Antioxidants (Basel, Switzerland) May 2024The level of tumor necrosis factor-α (TNF-α) is upregulated during the development of pulmonary vascular remodeling and pulmonary hypertension. A hallmark of...
The level of tumor necrosis factor-α (TNF-α) is upregulated during the development of pulmonary vascular remodeling and pulmonary hypertension. A hallmark of pulmonary arterial (PA) remodeling is the excessive proliferation of PA smooth muscle cells (PASMCs). The purpose of this study is to investigate whether TNF-α induces PASMC proliferation and explore the potential mechanisms. PASMCs were isolated from 8-week-old male Sprague-Dawley rats and treated with 0, 20, or 200 ng/mL TNF-α for 24 or 48 h. After treatment, cell number, superoxide production, histone acetylation, DNA methylation, and histone methylation were assessed. TNF-α treatment increased NADPH oxidase activity, superoxide production, and cell numbers compared to untreated controls. TNF-α-induced PASMC proliferation was rescued by a superoxide dismutase mimetic tempol. TNF-α treatment did not affect histone acetylation at either dose but did significantly decrease DNA methylation. DNA methyltransferase 1 activity was unchanged by TNF-α treatment. Further investigation using QRT-RT-PCR revealed that GADD45-α, a potential mediator of DNA demethylation, was increased after TNF-α treatment. RNAi inhibition of GADD45-α alone increased DNA methylation. TNF-α impaired the epigenetic mechanism leading to DNA hypomethylation, which can be abolished by a superoxide scavenger tempol. TNF-α treatment also decreased H3-K4 methylation. TNF-α-induced PASMC proliferation may involve the H3-K4 demethylase enzyme, lysine-specific demethylase 1 (LSD1). TNF-α-induced PASMC proliferation may be partly associated with excessive superoxide formation and histone and DNA methylation.
PubMed: 38929115
DOI: 10.3390/antiox13060677 -
International Journal of Molecular... Jun 2024Treatment of critically ill patients with venovenous (V-V) extracorporeal membrane oxygenation (ECMO) has gained wide acceptance in the last few decades. However, the...
New Insights into Hepatic and Intestinal Microcirculation and Pulmonary Inflammation in a Model of Septic Shock and Venovenous Extracorporeal Membrane Oxygenation in the Rat.
Treatment of critically ill patients with venovenous (V-V) extracorporeal membrane oxygenation (ECMO) has gained wide acceptance in the last few decades. However, the use of V-V ECMO in septic shock remains controversial. The effect of ECMO-induced inflammation on the microcirculation of the intestine, liver, and critically damaged lungs is unknown. Therefore, the aim of this study was to measure the hepatic and intestinal microcirculation and pulmonary inflammatory response in a model of V-V ECMO and septic shock in the rat. Twenty male Lewis rats were randomly assigned to receive V-V ECMO therapy or a sham procedure. Hemodynamic data were measured by a pressure-volume catheter in the left ventricle and a catheter in the lateral tail artery. Septic shock was induced by the intravenous infusion of lipopolysaccharide (1 mg/kg). During V-V ECMO therapy, rats received lung-protective ventilation. The hepatic and intestinal microcirculation was assessed by micro-lightguide spectrophotometry after median laparotomy for 2 h. Systemic and pulmonary inflammation was measured by enzyme-linked immunosorbent assays of plasma and bronchoalveolar lavage (BAL), respectively, which included tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), IL-10, C-X-C motif ligand 2 (CXCL2), and CXCL5. Reduced oxygen saturation and relative hemoglobin concentration were measured in the hepatic and intestinal microcirculation during treatment with V-V ECMO. These animals also showed increased systolic, mean, and diastolic blood pressures. While no differences in left ventricular ejection fraction were observed, animals in the V-V ECMO group presented an increased heart rate, stroke volume, and cardiac output. Blood gas analysis showed dilutional anemia during V-V ECMO, whereas plasma analysis revealed a decreased concentration of IL-10 during V-V ECMO therapy, and BAL measurements showed increased concentrations of TNF-α, CXCL2, and CXCL5. Rats treated with V-V ECMO showed impaired microcirculation of the intestine and liver during septic shock despite increased blood pressure and cardiac output. Despite lung-protective ventilation, increased pulmonary inflammation was recognized during V-V ECMO therapy in septic shock.
Topics: Animals; Microcirculation; Extracorporeal Membrane Oxygenation; Male; Rats; Shock, Septic; Rats, Inbred Lew; Intestines; Liver; Disease Models, Animal; Pneumonia; Hemodynamics; Tumor Necrosis Factor-alpha
PubMed: 38928327
DOI: 10.3390/ijms25126621 -
Bioengineering (Basel, Switzerland) Jun 2024Right-sided mechanical support of the Fontan circulation by existing devices has been compounded by the cross-sectional design of vena cava anastomosis to both pulmonary...
Right-sided mechanical support of the Fontan circulation by existing devices has been compounded by the cross-sectional design of vena cava anastomosis to both pulmonary arteries. Our purpose was to investigate whether increasing inferior vena cava (IVC) flow with a rotary blood pump in the IVC only in an ovine animal model of Fontan would lead to acceptable superior vena cava (SVC) pressure. To achieve this, a Fontan circulation was established in four female sheep by anastomosing the SVC to the main pulmonary artery (MPA) and by interposing a Dacron graft between the IVC and the MPA. A rotary blood pump was then introduced in the graft, and the effect of incremental flows was observed at increasing flow regimen. Additionally, to stimulate increased pulmonary resistance, the experience was repeated in each animal with the placement of a restrictive band on the MPA distally to the SVC and Dacron graft anastomosis. Circulatory support of IVC flow alone increased the systemic cardiac output significantly, both with and without banding, indicating the feasibility of mechanical support of the Fontan circulation by increasing the flow only in the inferior vena cava. The increase in SVC pressure remained within acceptable limits, indicating the potential effectiveness of this mode of support. The findings suggest that increasing the flow only in the inferior vena cava is a feasible method for mechanical support of the Fontan circulation, potentially leading to an increase in cardiac output with acceptable increases in superior vena cava pressure.
PubMed: 38927830
DOI: 10.3390/bioengineering11060594 -
Italian Journal of Pediatrics Jun 2024Arterial switch operation (ASO) is the standard surgical choice for D-transposition of great arteries (D-TGA). However, the implications of ASO on pulmonaries,...
Pulmonary, aorta, and coronary arteries post-arterial switch in transposition of great arteries: intermediate-term surveillance utilizing conventional echocardiography and cardiac multislice computed tomography.
BACKGROUND
Arterial switch operation (ASO) is the standard surgical choice for D-transposition of great arteries (D-TGA). However, the implications of ASO on pulmonaries, coronaries, and aorta have not been adequately investigated. The current study evaluates arterial morphologic changes post-ASO at intermediate-term surveillance.
METHODS
From May 2021 to May 2022, patients with D-TGA who underwent ASO for more than six months were recruited. Preoperative and operative data were collected. Patients were assessed using echocardiography (ECHO) and multislice CT angiography (MSCT) to evaluate pulmonary, coronary, and aortic arterial anatomy.
RESULTS
Twenty patients were included with median age of 11 (10-23.25) days at ASO and 14 (7.25-32.75) months on last follow-up. Neo-aortic regurgitation was detected in 12(60%) and neo-pulmonary regurgitation in 3 (15%). Using ECHO, complete evaluation of pulmonary arteries (PAs) was not achieved in 35% and incomplete coronaries assessment in 40% of cases. No stenosis was detected in coronaries using MSCT, although coronary anomalies were found in 9/20 (45%). Dilated Aortic annulus was detected in 16/20 (80%), dilated aortic root in 18/20 (90%), and dilated sinotubular junction in 70%. Right PA stenosis was diagnosed in 10/20 (50%) and left PA(LPA) stenosis in 7/20 (35%). Although Z-score of PAs did not correlate with aortic data, LPA bending angle was positively correlated to neo-aortic root diameter and Z-score (rho = 0.65,p = 0.016; rho = 0.69,p = 0.01), respectively.
CONCLUSION
Echocardiography alone is not a conclusive surveillance tool for detecting late post-ASO anatomic changes in D-TGA patients. Cardiac MSCT should be considered for comprehensive evaluation on the intermediate-term follow-up post-ASO to accurately track morphologic abnormalities in the aorta, pulmonary, and coronary arteries.
Topics: Humans; Male; Female; Transposition of Great Vessels; Echocardiography; Multidetector Computed Tomography; Infant; Infant, Newborn; Arterial Switch Operation; Pulmonary Artery; Child, Preschool; Coronary Vessels; Aorta; Retrospective Studies; Computed Tomography Angiography; Follow-Up Studies
PubMed: 38926831
DOI: 10.1186/s13052-024-01686-x -
Journal of Cardiothoracic Surgery Jun 2024As the pediatric patient with right pulmonary artery agenesis (PAA) matured, she progressively presented symptoms of pulmonary hypertension and hemoptysis. There is... (Review)
Review
Embolization treatment of right pulmonary artery agenisis with patent ductus arteriosus causing pulmonary hypertension and hemoptysis: a case report and literature review.
As the pediatric patient with right pulmonary artery agenesis (PAA) matured, she progressively presented symptoms of pulmonary hypertension and hemoptysis. There is limited clinical literature on this condition, and currently, there is no consensus regarding its diagnosis and treatment. This article presents a case study of a 16-year-old female patient with right pulmonary artery hypoplasia, providing a comprehensive summary and analysis of her developmental progression, pathology, diagnosis, and treatment.
Topics: Humans; Female; Hemoptysis; Pulmonary Artery; Adolescent; Embolization, Therapeutic; Hypertension, Pulmonary; Ductus Arteriosus, Patent
PubMed: 38926785
DOI: 10.1186/s13019-024-02883-9 -
Endocrine Journal Jun 2024Cushing's syndrome, a clinical condition characterized by hypercortisolemia, exhibits distinct clinical signs and is associated with cyclic cortisol secretion in some...
Cushing's syndrome, a clinical condition characterized by hypercortisolemia, exhibits distinct clinical signs and is associated with cyclic cortisol secretion in some patients. The clinical presentation of cyclic Cushing's syndrome can be ambiguous and its diagnosis is often challenging. We experienced a 72-year-old woman with cyclic ACTH-dependent Cushing's syndrome caused by a pulmonary carcinoid tumor. Diagnosis was challenging because of the extended trough periods, and the responsible lesion was initially unidentified. A subsequent follow-up computed tomography revealed a pulmonary lesion, and ectopic ACTH secretion from this lesion was confirmed by pulmonary artery sampling. Despite the short peak secretion period of ACTH (approximately one week), immunostaining of the surgically removed tumor confirmed ACTH positivity. Interestingly, stored plasma chromogranin A levels were elevated during both peak and trough periods. The experience in evaluating this patient prompted us to investigate the potential use of plasma chromogranin A as a diagnostic marker of ACTH-dependent Cushing's syndrome. A retrospective study was conducted to determine the efficacy of plasma chromogranin A in three patients with ectopic ACTH syndrome (EAS), including the present case, and six patients with Cushing's disease (CD) who visited our hospital between 2018 and 2021. Notably, plasma chromogranin A levels were higher in patients with EAS than in those with CD. Additionally, a chromogranin A level in the present case during the trough phase was lower than that in the peak phase, and was similar to those in CD patients. The measurement of plasma chromogranin A levels could aid in differentiating EAS from CD.
PubMed: 38925945
DOI: 10.1507/endocrj.EJ24-0128 -
BMJ (Clinical Research Ed.) Jun 2024To investigate the incidence of cardiovascular disease (CVD) overall and by age, sex, and socioeconomic status, and its variation over time, in the UK during 2000-19.
OBJECTIVE
To investigate the incidence of cardiovascular disease (CVD) overall and by age, sex, and socioeconomic status, and its variation over time, in the UK during 2000-19.
DESIGN
Population based study.
SETTING
UK.
PARTICIPANTS
1 650 052 individuals registered with a general practice contributing to Clinical Practice Research Datalink and newly diagnosed with at least one CVD from 1 January 2000 to 30 June 2019.
MAIN OUTCOME MEASURES
The primary outcome was incident diagnosis of CVD, comprising acute coronary syndrome, aortic aneurysm, aortic stenosis, atrial fibrillation or flutter, chronic ischaemic heart disease, heart failure, peripheral artery disease, second or third degree heart block, stroke (ischaemic, haemorrhagic, and unspecified), and venous thromboembolism (deep vein thrombosis or pulmonary embolism). Disease incidence rates were calculated individually and as a composite outcome of all 10 CVDs combined and were standardised for age and sex using the 2013 European standard population. Negative binomial regression models investigated temporal trends and variation by age, sex, and socioeconomic status.
RESULTS
The mean age of the population was 70.5 years and 47.6% (n=784 904) were women. The age and sex standardised incidence of all 10 prespecified CVDs declined by 19% during 2000-19 (incidence rate ratio 2017-19 2000-02: 0.80, 95% confidence interval 0.73 to 0.88). The incidence of coronary heart disease and stroke decreased by about 30% (incidence rate ratios for acute coronary syndrome, chronic ischaemic heart disease, and stroke were 0.70 (0.69 to 0.70), 0.67 (0.66 to 0.67), and 0.75 (0.67 to 0.83), respectively). In parallel, an increasing number of diagnoses of cardiac arrhythmias, valve disease, and thromboembolic diseases were observed. As a result, the overall incidence of CVDs across the 10 conditions remained relatively stable from the mid-2000s. Age stratified analyses further showed that the observed decline in coronary heart disease incidence was largely restricted to age groups older than 60 years, with little or no improvement in younger age groups. Trends were generally similar between men and women. A socioeconomic gradient was observed for almost every CVD investigated. The gradient did not decrease over time and was most noticeable for peripheral artery disease (incidence rate ratio most deprived least deprived: 1.98 (1.87 to 2.09)), acute coronary syndrome (1.55 (1.54 to 1.57)), and heart failure (1.50 (1.41 to 1.59)).
CONCLUSIONS
Despite substantial improvements in the prevention of atherosclerotic diseases in the UK, the overall burden of CVDs remained high during 2000-19. For CVDs to decrease further, future prevention strategies might need to consider a broader spectrum of conditions, including arrhythmias, valve diseases, and thromboembolism, and examine the specific needs of younger age groups and socioeconomically deprived populations.
Topics: Humans; Female; Male; United Kingdom; Incidence; Aged; Middle Aged; Cardiovascular Diseases; Adult; Aged, 80 and over; Social Class; Age Distribution; Sex Distribution; Young Adult
PubMed: 38925788
DOI: 10.1136/bmj-2023-078523 -
JACC. Cardiovascular Interventions Jun 2024Right ventricular impairment is common among patients undergoing transcatheter edge-to-edge repair for secondary mitral regurgitation (SMR). Adherence to... (Observational Study)
Observational Study
BACKGROUND
Right ventricular impairment is common among patients undergoing transcatheter edge-to-edge repair for secondary mitral regurgitation (SMR). Adherence to guideline-directed medical therapy (GDMT) for heart failure is poor in these patients.
OBJECTIVES
The aim of this study was to evaluate the impact of GDMT on long-term survival in this patient cohort.
METHODS
Within the EuroSMR (European Registry of Transcatheter Repair for Secondary Mitral Regurgitation) international registry, we selected patients with SMR and right ventricular impairment (tricuspid annular plane systolic excursion ≤17 mm and/or echocardiographic right ventricular-to-pulmonary artery coupling <0.40 mm/mm Hg). Titrated guideline-directed medical therapy (GDMT) was defined as a coprescription of 3 drug classes with at least one-half of the target dose at the latest follow-up. The primary outcome was all-cause mortality at 6 years.
RESULTS
Among 1,213 patients with SMR and right ventricular impairment, 852 had complete data on medical therapy. The 123 patients who were on GDMT showed a significantly higher long-term survival vs the 729 patients not on GDMT (61.8% vs 36.0%; P < 0.00001). Propensity score-matched analysis confirmed a significant association between GDMT and higher survival (61.0% vs 43.1%; P = 0.018). GDMT was an independent predictor of all-cause mortality (HR: 0.61; 95% CI: 0.39-0.93; P = 0.02 for patients on GDMT vs those not on GDMT). Its association with better outcomes was confirmed among all subgroups analyzed.
CONCLUSIONS
In patients with right ventricular impairment undergoing transcatheter edge-to-edge repair for SMR, titration of GDMT to at least one-half of the target dose is associated with a 40% lower risk of all-cause death up to 6 years and should be pursued independent of comorbidities.
Topics: Humans; Female; Male; Mitral Valve Insufficiency; Registries; Aged; Treatment Outcome; Time Factors; Ventricular Dysfunction, Right; Ventricular Function, Right; Risk Factors; Practice Guidelines as Topic; Guideline Adherence; Cardiac Catheterization; Cardiovascular Agents; Europe; Aged, 80 and over; Risk Assessment; Echocardiography, Transesophageal; Mitral Valve; Middle Aged; Recovery of Function
PubMed: 38925749
DOI: 10.1016/j.jcin.2024.04.025