Progressive Dilatation Research Articles

Assessing Right Ventricle Over Time in Patients on Veno-Venous Extracorporeal Membrane Oxygenation: Insights From Serial Echocardiography.

Extracorporeal membrane oxygenation (ECMO) is often used in acute respiratory distress syndrome (ARDS) with refractory hypoxemia. There is limited literature highlighting the development of right ventricular (RV) failure while on ECMO. We conducted a retrospective multicenter observational study including 70 patients who were placed on veno-venous (VV)-ECMO for respiratory failure at Mayo Clinic, Jacksonville, and Mayo Clinic, Rochester, between January 2018 and June 2022 and had at least two post-ECMO transthoracic echoes. The primary outcomes were the incidence and progression of RV dysfunction and dilatation. The secondary outcome was in-patient mortality. Among 70 patients in our cohort, 60.6% had a normal RV function at the time of ECMO placement, whereas only 42% had a normal RV function at the second post-ECMO echo. On multinomial regression, a moderate decrease in RV function was associated with ECMO flow (odds ratio [OR] = 2.32, p = 0.001) and ECMO duration (OR = 1.01, p = 0.01). A moderately dilated RV size was also associated with ECMO flow (OR = 2.62, p < 0.001) and ECMO duration (OR = 1.02, p = 0.02). An increasing degree of RV dysfunction was associated with worse outcomes. Our study showed that the increasing duration and flow of VV-ECMO correlated with progressive RV dilatation and dysfunction, which were associated with poor survival.

CHANGES IN LEFT ATRIAL VOLUME DURING ECHOSTRESS IN PATIENTS UNDERGOING MITRAL VALVE PLASTIC CARDIAC SURGERY

Abstract Mitral Regurgitation (MR) is characterized by a high morbidity and mortality that often finds a solution only in the reparative surgical treatment, in particular in presence of myxomatous degeneration that cause the prolapse of one or both leaflets. This results in an increase in diastolic pressure that leads to a progressive dilation of the left atrium. The increase in Left Atrium Volume Index (LAVI) during stress test represents a negative prognostic factor in the clinical evolution of many pathologies, such as ischemic heart disease, hypertrophic cardiomyopathy, heart failure. An increase in peak/rest LAVI &amp;gt;6.8 ml/m2 correlates with a higher incidence of heart failure decompensation, reduced left ventricular contractile reserve (LVCR), pulmonary congestion. We evaluate the effect of MR reparative surgery on the changes of LAVI during stress–echo. We enrolled 19 patients, 11 females and 8 males, affected by MR candidate to cardiac surgery. We performed a physical stress–echo test by using the ABCDE protocol suggested by the Italian Society of Echocardiography and Cardiovascular Imaging (SIECVI), before and after 12 weeks from surgery. During each test, the changes in LAVI (ΔLAVI) expressed as peak/rest difference in ml/m2 was measured. In addition, the prognostic score deriving from the sum of the ABCDE criteria was calculated, such as the LVCR (C parameter of the score) that represents a parameter of the force deriving from the hemodynamic changes during the test. In all patients we observed a significant reduction in ΔLAVI (8.4+0.5 mL/m2 vs 9.7+0.7 mL/m2; p&amp;lt;0.0001). In addition, there was a significant reduction in the ABCDE prognostic score (from 4.19+0.43 to 3.48+0.37; p=0.002), secondary to the increase in the LVCR observed approximately 3 months after surgery (from 1.77 mmHg/ml to 2.44 mmHg/ml, p&amp;lt;0.0001), as well as a significant reduction in pulmonary congestion during stress (B parameter). There were no significant changes in ejection fraction, wall motion score index–WMSI (A parameter), coronary reserve (D parameter) and heart rate reserve (E parameter). These data demonstrate for the first time that mitral valve plastic surgery is able to reduce the ΔLAVI during stress echocardiography in patients with severe MR. The surgical procedure also resulted in both an improvement in the LVCR and a reduction in the degree of pulmonary congestion, that ultimately led to an improvement in the ABCDE prognostic score.

Late Presentation of Pulmonary Hypertension Crisis Concurrent with Atrial Arrhythmia after Atrial Septal Defect Device Closure

Background: ASD occurs when there is a septal defect between the right and left atria, resulting in a left-to-right shunt that increases the volume of the right heart and pulmonary circulation. Increased pulmonary resistance can lead to pulmonary hypertension (PH), resulting in progressive deterioration of right ventricular function, leading to right heart failure and death. Prolonged elevation of atrial pressure induces progressive atrial dilatation and electrophysiological remodelling. Together with autonomic modulation, this leads to atrial arrhythmias (AAs). Patients with significant shunts leading to ventricular volume overload are considered for ASD closure. However, in some cases, PH occurs after ASD closure.  Case Presentation: We report a 21 yo man diagnosed with ASD Secundum Post Closure with Device (September 1th, 2023) and Pulmonary Hypertension Crisis. The left atria (LA), right atria (RA) and right ventricle (RV) were dilated. We also found moderate mitral regurgitation, severe tricuspid regurgitation, and mild to moderate pulmonary regurgitation. There was a decline in systolic function in the right ventricle, and grade III diastolic dysfunction in left ventricle. There was a well-seated device with no residual shunt on interatrial septal. The pulmonary arteries were confluence and dilated. From ECG we found atrial flutter with variable conduction. This patient was transferred to HCU. This patient treated with digoxin, furosemide, milrinon, ceftriaxone, miniaspi, sildenafil, electrophysiology, and 3D ablation.  Conclusion: Pulmonary hypertension can occur in cases of congenital heart defects, such as ASD. The operative management of ASD is closure of the ASD, but in some unique groups, this can lead to pulmonary hypertensive crisis after its closure.

Secondary infertility due to necrospermia in men with autosomal-dominant polycystic kidney disease: a report of two cases.

Autosomal-dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disease characterized by the formation of numerous cysts in organs other than the kidneys. Although female patients with ADPKD do not have direct fertility problems, infertility in male patients may arise following the formation of cystic lesions in the lower seminal tract, which impair the function of spermatozoa. Generally, the treatment strategy for necrospermia depends on the severity of sperm viability, and intracytoplasmic sperm injection may be offered to patients with necrospermia. We report two cases of secondary infertility in men with ADPKD. These men experienced an inability to reproduce naturally after the previous birth of a child, suggesting a progressive deterioration of semen quality. Semen analysis showed necrospermia in both patients, and transrectal ultrasound revealed marked dilatation of the seminal vesicles bilaterally. The main cause of secondary infertility in male patients with ADPKD is sperm death resulting from progressive dilatation of seminal vesicles. Further research is needed on the appropriate follow-up schedule for men with ADPKD who desire to reproduce naturally.

PROFILE OF INDUCED LABOUR IN UNCOMPLICATED PREGNANCIES WITH UNFAVOURABLE MODIFIEDS BISHOP SCORE IN A TERTIARY CARE CENTRE

Background: Induction of Labor is a non-spontaneous initiation of uterine contractions before onset of spontaneous labour that results in progressive dilatation with effacement of cervix and further descent of the presenting part of fetus, leading to safe vaginal delivery of the baby. ACOG has an extensive list of recommendations on delivery timing for various complicated and uncomplicated pregnancies. Pharmacological methods are most commonly deployed for induction in patients with poor bishopÂ’s score. The aim of this study is to determine maternal and perinatal outcome in induced labour in medically uncomplicated pregnancies. Methods: This is a hospital based retrospective observational study conducted for a duration of 11 months on 422 patients admitted in our labour room with unfavourable modified bishops score given induction of labour for various reasons after ruling out any contraindication for vaginal delivery. Results: In our study of 422 participants, majorities was term pregnancies (93.36%) and were induced by dinoprostone gel. Most common indication for IOL was postdated pregnancy (36.49%) and 67.3% patients underwent vaginal delivery. 27.7% of all vaginal deliveries required additional doses of dinoprostone. Most common indication for emergency caesarian section was FIOL (63.77%). All neonates were born alive and 32.46% neonates got admitted in NICU, most common indication being neonatal jaundice.42.42% cases developed complication of induction most common being MSL(17.54%). Conclusion: Induction of labor is beneficial and safe even in uncomplicated pregnancies. Although there is increased incidence of caesarian section, induction should be performed once risk of continuing pregnancy outweighs risk of termination.

Correlation of ECG and cardiac MRI for assessment of ventricular hypertrophy and dilatation in adults with repaired tetralogy of Fallot

BackgroundSurgically repaired Tetralogy of Fallot (rTOF) is associated with progressive right ventricular hypertrophy (RVH) and dilation (RVD). Accurate estimation of RVH/RVD is vital for the ongoing management of this patient population. The utility of the ECG in evaluating patients with rTOF with pre-existing right bundle branch block (RBBB) has not been studied. We aimed to determine the sensitivity/specificity of currently established ECG criteria in detecting RVH/RVD in this patient population. MethodsWe included consecutive patients diagnosed with rTOF who underwent CMR performed at our regional referral centre between January 2012 and December 2019. Each CMR was assessed for LVH, LVD, RVH and or RVD. The ECG corresponding to the CMR was then used to determine RVH/LVH for specificity and sensitivity analysis. ResultsOur study included 163 consecutive rTOF patients. The specificity for ECG-based criteria for LVH was 100.00% (95% C.I. (87.75, 100.00)), and the sensitivity was 7.19% (95% C.I. (3.15, 12.83)). When RBBB was present, specificity for RVH was 100.00% (95% C.I. (84.56, 100.00)), and sensitivity was 7.69% (95% C.I. (3.75, 13.69)). When RBBB was absent, specificity for RVH was 100.00% (95% C.I. (15.81, 100.00)), and sensitivity was 0.00% (95% C.I. (0.00, 33.63)). A regression model with the entire group of 163 ToF patients, based on the Sokolow-Lyon criterion (sum of R in V1 + S in V5/V6), produced a new suggested criterion for the diagnosis of RVH in patients with rTOF, which was a sum of R in V1 + S in V5/V6 greater than 13.25 mm. This model's sensitivity for RVH detection was 69.1%, and specificity was 36.8%. ConclusionsStandard ECG voltage criteria have poor sensitivity for detecting right and left ventricular chamber hypertrophy and dilatation in patients with rTOF, so current ECG criteria should not be used to monitor RVH/RVD in this patient population.

Comparison of open thoracoabdominal repair for chronic aortic dissections and aneurysms

ObjectiveAortic dissection is common in patients undergoing open surgical repair of thoracoabdominal aortic aneurysms (TAAAs). Most often, dissection is chronic and is associated with progressive aortic dilatation. Because contemporary outcomes in chronic dissection are not clearly understood, we compared patient characteristics and outcomes after open TAAA repair between patients with chronic dissection and those with non-dissection aneurysm. MethodsWe retrospectively analyzed data from 3470 open TAAA repairs performed in a single practice. Operations were for non-dissection aneurysm in 2351 (67.8%) and chronic dissection in 1119 (32.2%). Outcomes included operative mortality and adverse events, a composite variable comprising operative death and persistent (present at discharge) stroke, paraplegia, paraparesis, and renal failure necessitating dialysis. Logistic regression identified predictors of operative mortality and adverse events. Time-to-event analyses examined survival, death, repair failure, subsequent progressive repair, and survival free of failure or subsequent repair. ResultsCompared with patients with non-dissection aneurysm, those with chronic dissection were younger, had fewer atherosclerotic risk factors, and were more likely to have heritable thoracic aortic disease and undergo extent II repair. The operative mortality rate was 8.5% (n = 296) overall and was higher in non-dissection aneurysm patients (n = 217; 9.2%) than in chronic dissection patients (n = 79; 7.1%; P = .03). Adverse events were less frequent (P = .01) in patients with chronic dissection (n = 145; 13.0%), 22 (2.0%) of whom had persistent paraplegia. Chronic dissection was not predictive of operative mortality (P = .5) or adverse events (P = .6). Operative mortality and adverse events, respectively, were independently predicted by emergency repair (odds ratio [OR], 3.46 and 2.87), chronic kidney disease (OR, 1.74 and 1.81), extent II TAAA repair (OR, 1.44 and 1.73), increasing age (OR, 1.04/year and 1.04/year), and increasing aortic cross-clamp time (OR, 1.02/minutes and 1.02/minutes). Patients with chronic dissection had lower 10-year unadjusted mortality (42% vs 69%) but more frequent repair failure (5% vs 3%) and subsequent repair for progressive aortic disease (11% vs 5%) than patients with non-dissection aneurysm (P < .001); these differences were no longer statistically significant after adjustment. ConclusionsOutcomes of open TAAA repair vary by aortic disease type. Emergency repairs and atherosclerotic diseases most commonly occur in patients with non-dissection aneurysm and independently predict operative mortality. Repair of chronic dissection is associated with low rates of adverse events, including operative mortality and persistent paraplegia, along with reasonable late survival and good durability. However, patients with chronic dissection tend to more commonly undergo subsequent repair to treat progressive aortic disease, which emphasizes the need for robust long-term imaging surveillance protocols.

Configuration of the neoaortic root after chimney reconstruction in the Norwood procedure.

After staged reconstruction for hypoplastic left heart syndrome, the neoaortic root tends to dilate, and the incidence of significant neoaortic valve insufficiency increases with time. This study aimed to evaluate the mid-term outcomes of the neoaortic root geometries and valve function after chimney reconstruction in the Norwood procedure. Between 2013 and 2021, 20 consecutive patients who underwent chimney reconstruction during the Norwood procedure for hypoplastic left heart syndrome and its variants in our institution were enrolled. The actual diameters of the following points were measured, and Z-scores were calculated based on the normal aortic root geometries using the long axis view of echocardiography at the pre-Norwood stage and the lateral view of angiography at pre-Glenn, pre-Fontan, post-Fontan and follow-up (age 5-6 years) stages: neoaortic valve annulus; sinus of Valsalva; sinotubular junction; and ascending aorta just proximal to the anastomosis to the aortic arch. The degree of neoaortic valve regurgitation was evaluated by echocardiography at each stage. The median follow-up period was 3.9 years. Neoaortic roots after chimney reconstruction were spared from progressive dilation over time. With growth, the conical configuration of the neoaortic roots was preserved without geometrical distortion. The Z-scores of the annulus, sinus of Valsalva, sinotubular junction and ascending aorta ranged roughly from 4 to 6, 4 to 6, 2 to 4 and 0 to 2, respectively. All neoaortic valves at each stage had mild or no regurgitation. Chimney reconstruction prevented neoaortic root dilation and avoided significant neoaortic valve regurgitation in the mid-term. These neoaortic dimensions with smooth flow profiles in the neoaorta after chimney reconstruction may have contributed to the current results. Further studies are needed to clarify the long-term outcomes.

Predicting feature genes correlated with immune infiltration in patients with abdominal aortic aneurysm based on machine learning algorithms

Abdominal aortic aneurysm (AAA) is a condition characterized by a pathological and progressive dilatation of the infrarenal abdominal aorta. The exploration of AAA feature genes is crucial for enhancing the prognosis of AAA patients. Microarray datasets of AAA were downloaded from the Gene Expression Omnibus database. A total of 43 upregulated differentially expressed genes (DEGs) and 32 downregulated DEGs were obtained. Function, pathway, disease, and gene set enrichment analyses were performed, in which enrichments were related to inflammation and immune response. AHR, APLNR, ITGA10 and NR2F6 were defined as feature genes via machine learning algorithms and a validation cohort, which indicated high diagnostic abilities by the receiver operating characteristic curves. The cell-type identification by estimating relative subsets of RNA transcripts (CIBERSORT) method was used to quantify the proportions of immune infiltration in samples of AAA and normal tissues. We have predicted AHR, APLNR, ITGA10 and NR2F6 as feature genes of AAA. CD8 + T cells and M2 macrophages correlated with these genes may be involved in the development of AAA, which have the potential to be developed as risk predictors and immune interventions.

Aortic dilation in adults with repaired tetralogy of Fallot: a single-centre study.

Tetralogy of Fallot is the most prevalent cyanotic CHD. With the advent of advanced surgical methods, the majority of tetralogy of Fallot patients reach adulthood. However, many need re-intervention for the residual anomalies including residual right ventricular outflow obstruction, pulmonary regurgitation, residual ventricular septal defects, and progressive aortic dilatation. Aortic dilation could lead to aortic regurgitation or dissection requiring surgical correction. In the current study, we aimed to determine the prevalence and outcomes of aortic root dilatation in adults with repaired tetralogy of Fallot in our tertiary care centre. In this retrospective study, 730 consecutive patients with history of repaired tetralogy of Fallot were included. Aortic diameter at the level of annulus, the sinus of Valsalva, sinotubular junction, and the ascending aorta as measured by echocardiography were evaluated. Prevalence of outcomes necessitating re-intervention including aortic regurgitation and dissection were recorded. The mean size of annulus, sinus of Valsalva, sinotubular-junction, and ascending aorta in the latest available echocardiography of patients were 2.4+/-0.4 cm, 3.3+/-0.5 cm, 2.9+/-0.5cm, and 3.2+/-0.5cm, respectively. Prevalence of dilatation of sinus of Valsalva, dilation of Ascending aorta, sinotubular-junction, and aortic annulus was 28.7%, 21%, 8.3%, and 1 %, respectively. Five patients had severe aortic regurgitation (0.6%) and underwent surgical repair. One of these patients presented with acute aortic dissection. Aortic dilation is common in tetralogy of Fallot but prevalence of redo surgery for aortic dilation, regurgitation, and adverse events including acute dissection is low.

Novel Biomarkers in Early Detection of Heart Failure: A Narrative Review.

Heart failure (HF) represents a significant global health challenge, characterized by a variety of symptoms resulting from cardiac dysfunction. This dysfunction often leads to systemic and pulmonary congestion. The pathophysiology of HF is complex, involving stimulation of the sympathetic nervous system, which is insufficiently balanced by the release of natriuretic peptide. This imbalance leads to progressive hypertrophy and dilatation of the heart's chambers, impairing its pumping efficiency and increasing the risk of arrhythmias and conduction disorders. The prevalence of HF is exceptionally high in industrialized nations and is expected to increase owing to an aging population and advancements in diagnostic methods. This study emphasizes the critical role of early diagnosis in reducing morbidity and mortality associated with HF, focusing specifically on the evolving importance of biomarkers in managing this condition. Biomarkers have played a key role in transforming the diagnosis and treatment of HF. Traditional biomarkers such as b-type natriuretic peptide and N-terminal pro-b-type natriuretic peptide have been widely adopted for their cost-effectiveness and ease of access. However, the rise of novel biomarkers such as growth differentiation factor 15 and adrenomedullin has shown promising results, offering superior sensitivity and specificity. These new biomarkers enhance diagnostic accuracy, risk stratification, and prognostic evaluation in HF patients. Despite these advancements, challenges remain, such as limited availability, high costs, and the need for further validation in diverse patient populations. Through a comprehensive literature review across databases such as PubMed, Google Scholar, and the Cochrane Library, this study compiles and analyzes data from 18 relevant studies, offering a detailed understanding of the current state of HF biomarkers.The study examines both traditional and emerging biomarkers such as galectin-3 and soluble suppression of tumorigenicity 2 in HF, exploring their clinical roles and impact on patient outcomes.

Intermediate and long-term outcomes of transcatheter closure of congenital coronary cameral fistulas in 66 children

Objective: To evaluate the intermediate and long-term outcomes and technical aspects of transcatheter closure (TCC) of coronary cameral fistulas (CCF) in pediatric patients. Methods: This was a case-control study. All pediatric patients with CCF who underwent TCC between January 2005 and December 2019 were retrospectively reviewed. Data was collected from medical records, including demographic characteristics, procedural details, intraoperative and postoperative serious adverse events, follow-up results and prognosis. Patients with serious adverse events and without serious adverse events were compared regarding their clinical features and CCF characteristics. Comparisons between groups were performed with independent sample t test, chi-square test or Fisher exact test. Results: A total of 66 CCF patients (34 boys, 32 girls, 3.9 (1.9, 6.2) years old, 15 (11, 20) kg) underwent attempted TCC. All of the CCF were all medium or large fistulas including 55 proximal fistulas (83%) and 11 distal fistulas (17%). The CCF originated more frequently from the right coronary artery (38 cases (58%)), followed by the left coronary artery (28 cases (42%)). The incidence of coronary artery aneurysms (CAA) was 61% (40/66).Procedural treatment was achieved in 64 patients and procedural success was achieved in 59 patients (92%). Six (9%) serious adverse events occurred in 5 patients during the perioperative period. Acute complications included procedure-related death in one patient and acute myocardial infarction in one patient. Periprocedural complications occurred in 3 patients at one day postoperatively including acute myocardial infarction (2 cases), occluder detachment (1 case), and tricuspid chordae tendinae rupture (1 case). Clinical follow-up data were available in 58 of the 62 patients who underwent initial successful TCC with a follow-up period of 9.3 (6.5, 13.4) years. Ten adverse events occurred in 9 patients including 5 complications consisted of aortic valve perforation (1 case), coronary thrombosis (1 case), progressive aneurysmal dilation after reintervention (1 case), and new-onset tricuspid valve prolapse with significant regurgitation (2 cases) and large residual shunts due to fistula recanalization (5 cases). Therefore, the incidence of intermediate and long-term adverse events was 17% (10/58). During the periprocedural and follow-up period, 16 adverse events occurred in 13 patients, whereas no adverse events occurred in 51 patients. Patients with seriovs adverse events presented with larger proportion of large CCF (11/13 vs. 39% (20/51), P=0.005), giant CAA (10/13 vs.14% (7/51), P=0.030), and higher mean pulmonary artery pressure ((20±9) vs.(16±6) mmHg, 1 mmHg=0.133 kPa, t=2.02, P=0.048) compared to patients without serious adverse events. Conclusions: TCC in CCF children appears to be effective with favorable intermediate and long-term outcomes. Strict indication of TCC is mandatory.

Progressive Left Ventricular Remodeling for Predicting Mortality in Children With Dilated Cardiomyopathy: The Pediatric Cardiomyopathy Registry.

Pediatric dilated cardiomyopathy often leads to death or cardiac transplantation. We sought to determine whether changes in left ventricular (LV) end-diastolic dimension (LVEDD), LV end-diastolic posterior wall thickness, and LV fractional shortening (LVFS) over time may help predict adverse outcomes. We studied children up to 18 years old with dilated cardiomyopathy, enrolled between 1990 and 2009 in the Pediatric Cardiomyopathy Registry. Changes in LVFS, LVEDD, LV end-diastolic posterior wall thickness, and the LV end-diastolic posterior wall thickness:LVEDD ratio between baseline and follow-up echocardiograms acquired ≈1 year after diagnosis were determined for children who, at the 1-year follow-up had died, received a heart transplant, or were alive and transplant-free. Within 1 year after diagnosis, 40 (5.0%) of the 794 eligible children had died, 117 (14.7%) had undergone cardiac transplantation, and 585 (73.7%) had survived without transplantation. At diagnosis, survivors had higher median LVFS and lower median LVEDD Z scores. Median LVFS and LVEDD Z scores improved among survivors (Z score changes of +2.6 and -1.1, respectively) but remained stable or worsened in the other 2 groups. The LV end-diastolic posterior wall thickness:LVEDD ratio increased in survivors only, suggesting beneficial reverse LV remodeling. The risk for death or cardiac transplantation up to 7 years later was lower when LVFS was improved at 1 year (hazard ratio [HR], 0.83; P=0.004) but was higher in those with progressive LV dilation (HR, 1.45; P<0.001). Progressive deterioration in LV contractile function and increasing LV dilation are associated with both early and continuing mortality in children with dilated cardiomyopathy. Serial echocardiographic monitoring of these children is therefore indicated. URL: https://www.clinicaltrials.gov; Unique identifier: NCT00005391.

Assessing Nasal Epithelial Dynamics: Impact of the Natural Nasal Cycle on Intranasal Spray Deposition.

This study investigated the intricate dynamics of intranasal spray deposition within nasal models, considering variations in head orientation and stages of the nasal cycle. Employing controlled delivery conditions, we compared the deposition patterns of saline nasal sprays in models representing congestion (N1), normal (N0), and decongestion (P1, P2) during one nasal cycle. The results highlighted the impact of the nasal cycle on spray distribution, with congestion leading to confined deposition and decongestion allowing for broader dispersion of spray droplets and increased sedimentation towards the posterior turbinate. In particular, the progressive nasal dilation from N1 to P2 decreased the spray deposition in the middle turbinate. The head angle, in conjunction with the nasal cycle, significantly influenced the nasal spray deposition distribution, affecting targeted drug delivery within the nasal cavity. Despite controlled parameters, a notable variance in deposition was observed, emphasizing the complex interplay of gravity, flow shear, nasal cycle, and nasal morphology. The magnitude of variance increased as the head tilt angle increased backward from upright to 22.5° to 45° due to increasing gravity and liquid film destabilization, especially under decongestion conditions (P1, P2). This study's findings underscore the importance of considering both natural physiological variations and head orientation in optimizing intranasal drug delivery.

Dynamic changes in mitral valve extracellular matrix, tissue mechanics and function in a mouse model of Marfan syndrome

ObjectiveMouse models of Marfan syndrome (MFS) with Fibrillin 1 (Fbn1) variant C1041G exhibit cardiovascular abnormalities, including myxomatous valve disease (MVD) and aortic aneurism, with structural extracellular matrix (ECM) dysregulation. In this study, we examine the structure-function-mechanics relations of the mitral valve related to specific transitions in ECM composition and organization in progressive MVD in MFS mice from Postnatal day (P)7 to 1 year-of-age. Approach and resultsMechanistic links between mechanical forces and biological changes in MVD progression were examined in Fbn1C1041G/+ MFS mice. By echocardiography, mitral valve dysfunction is prevalent at 2 months with a decrease in cardiac function at 6 months, followed by a preserved cardiac function at 12 months. Mitral valve (MV) regurgitation occurs in a subset of mice at 2–6 months, while progressive dilatation of the aorta occurs from 2 to 12 months. Mitral valve tissue mechanical assessments using a uniaxial Permeabilizable Fiber System demonstrate decreased stiffness of MFS MVs at all stages. Histological and microscopic analysis of ECM content, structure, and fiber orientation demonstrate that alterations in ECM mechanics, composition, and organization precede functional abnormalities in Fbn1C1041G/+MFS MVs. At 2 months, ECM abnormalities are detected with an increase in proteoglycans and decreased stiffness of the mitral valve. By 6–12 months, collagen fiber remodeling is increased with abnormal fiber organization in MFS mitral valve leaflets. At the same time, matrifibrocyte gene expression characteristic of collagen-rich connective tissue is increased, as detected by RNA in situ hybridization and qPCR. Together, these studies demonstrate early prevalence of proteoglycans at 2 months followed by upregulation of collagen structure and organization with age in MVs of MFS mice. ConclusionsAltogether, our data indicate dynamic regulation of mitral valve structure, tissue mechanics, and function that reflect changes in ECM composition, organization, and gene expression in progressive MVD. Notably, increased collagen fiber organization and orientation, potentially dependent on increased matrifibrocyte cell activity, is apparent with altered mitral valve mechanics and function in aging MFS mice.

Interval changes in four-dimensional flow-derived in vivo hemodynamics stratify aortic growth in type B aortic dissection patients

BackgroundAortic diameter growth in type B aortic dissection (TBAD) is associated with progressive aortic dilation, resulting in increased mortality in patients with both de novo TBAD (dnTBAD) and residual dissection after type A dissection repair (rTAAD). Preemptive thoracic endovascular aortic repair may improve mortality in patients with TBAD, although it is unclear which patients may benefit most from early intervention. In vivo hemodynamic assessment using four-dimensional (4D) flow magnetic resonance imaging (MRI) has been used to characterize TBAD patients with growing aortas. In this longitudinal study, we investigated whether changes over time in 4D flow derived true and false lumen (TL, FL) hemodynamic parameters correlate with aortic growth rate which is a marker of increased risk. MethodsWe retrospectively identified TBAD patients with baseline and follow-up 4D flow MRI at least 120 days apart. Patients with TBAD intervention before baseline or between scans were excluded. 4D flow MRI data analysis included segmentation of the TL and FL, followed by voxel-wise calculation of TL and FL total kinetic energy (KE), maximum velocity (MV), mean forward flow (FF), and mean reverse flow (RF). Changes over time (Δ) were calculated for all hemodynamic parameters. Maximal diameter in the descending aorta was measured from MR angiogram images acquired at the time of 4D flow. Aortic growth rate was defined as the change in diameter divided by baseline diameter and standardized to scan interval. Results32 patients met inclusion criteria (age: 56.9±14.1 years, Female: 13, n=19 rTAAD, n=13 dnTBAD). Mean follow up time was 538 days (range: 135-1689). Baseline aortic diameter did not correlate with growth rate. In the entire cohort, Δ FL MV (rho=0.37, p=.04) and Δ FL RF (rho=0.45, p=0.01) correlated with growth rate. In rTAAD only, Δ FL MV (rho=0.48, p=.04) and Δ FL RF (rho=0.51, p=0.03) correlated with growth rate, while in dnTBAD only, Δ TL KE (rho=0.63, p=.02) and Δ TL MV (rho=0.69, p=.01) correlated with growth rate. Conclusions4D flow derived longitudinal hemodynamic changes correlate with aortic growth rate in TBAD and may provide additional prognostic value for risk stratification. 4D flow MRI could be integrated into existing imaging protocols to allow for identification of TBAD patients who would benefit from preemptive surgical or endovascular intervention.

Similar Distribution between EPA-containing Phosphatidylcholine and Mesenchymal Stem Marker Positive Cells in the Aortic Wall of Abdominal Aortic Aneurysm Model Rat Fed a Low-EPA Content Diet.

Abdominal aortic aneurysm (AAA) is a vascular disease characterized by progressive dilation of the abdominal aorta. Previous studies have suggested that dietary components are closely associated with AAA. Among those dietary components, eicosapentaenoic acid (EPA) is considered to have suppressive effects on AAA. In the AAA wall of AAA model animals bred under EPA-rich condition, the distribution of EPA-containing phosphatidylcholine (EPA-PC) has been reported to be similar to that of the markers of mesenchymal stem cells (MSCs) and M2 macrophages. These data suggest that the suppressive effects of EPA on AAA are related to preferential distribution of specific cells in the aortic wall. However, the distribution of EPA-PC in the AAA wall of AAA model animals fed a diet containing small amounts of EPA, which has not been reported to inhibit AAA, has not yet been explored. In the present study, we visualized the distribution of EPA-PCs in the AAA wall of AAA model animals fed a diet containing small amounts of EPA (1.5% EPA in the fatty acid composition) to elucidate the vasoprotective effects of EPA. Positive areas for markers of MSCs were significantly higher in the region where EPA-PC was abundant compared to the regions where EPA-PC was weakly detected, but not for markers of M2 macrophages, matrix metalloproteinase (MMP)-2, and MMP-9. The distribution of MSC markers was similar to that of EPA-PC but not that of M2 macrophages and MMPs. These data suggest preferential incorporation of EPA into MSCs under the conditions used in this study. The incorporation of EPA into certain cells may differ according to dietary conditions, which affect the development of AAA.

The application of 5E rehabilitation management mode in the nursing of patients with aortic dissection complicated by obstructive sleep apnea

ObjectiveThis study was designed to explore the effect of 5E rehabilitation mode (encouragement, education, exercise, employment, and evaluation) in patients with aortic dissection (AD) complicated by obstructive sleep apnea (OSA).MethodsPatients with Stanford type B AD (TBAD) complicated by OSA were admitted to Guangdong Provincial People’s Hospital from January 2019 to December 2020. They were randomly divided into an experimental group and a control group. After discharge, patients in the control group were given routine nursing and follow-up education, whereas patients in the experimental group were given 5E rehabilitation management mode–based nursing and follow-up education. Upon the nursing intervention, the differences in polysomnography (PSG) parameters, medication adherence, quality of life, blood pressure, and heart rate of patients between the two groups were compared. Logistic regression analysis was performed to evaluate the risk factors for the occurrence of adverse aortic events.ResultsA total of 89 patients were enrolled, 49 in the experimental group and 40 in the control group. After the intervention, the control of heart rate, systolic blood pressure, medication adherence, PSG parameters, and quality of life scores in the experimental group were significantly better than those in the control group (P<0.05). The incidence of adverse aortic events including aortic rupture and progressive aortic dilation in the experimental group was significantly lower than that in the control group (P < 0.05). Logistic regression analysis revealed that acute TBAD [odds ratio (OR) = 15.069; 95%confidence interval (CI), 1.738–130.652; P=0.014], history of chronic kidney disease (OR=10.342; 95%CI, 1.056–101.287; P=0.045), and apnea hypopnea index (AHI) ≥ 30 (OR=2.880; 95%CI, 1.081–9.51; P=0.036) were adverse factors affecting adverse aortic events; while 5E rehabilitation management mode (OR=0.063; 95%CI, 0.008–0.513; P=0.010) was a favorable factor for occurrence of adverse aortic events.ConclusionThe findings suggest that continuous nursing based on information carrier 5E rehabilitation management significantly enhanced medication adherence, improved patients’ overall quality of life, and decreased the incidence of adverse aortic events in patients TBAD patients and OSA.

Icariin improves cardiac function and remodeling via the TGF-β1/Smad signaling pathway in rats following myocardial infarction

BackgroundPostinfarction cardiac remodeling presents a compensatory mechanism aimed at mitigating congestive heart failure. It is distinguished by progressive dilatation and hypertrophy of the ventricular chambers, fibrotic alterations, and prolonged apoptosis of cardiomyocytes. The primary objective of this study was to assess the effects of icariin on myocardial fibrosis and ventricular remodeling in rats subjected to myocardial infarction (MI).MethodsMale Sprague‒Dawley (SD) rats were subjected to randomization and subsequently divided into distinct groups: the control group, the sham group (undergoing sham operation), the MI group (experiencing ligation of the left anterior descending artery), and the icariin group. Within the icariin group, rats were further categorized into three different dose groups based on the administered icariin dosage: the MI30 group (30 mg/kg/day), the MI60 group (60 mg/kg/day), and the MI120 group (120 mg/kg/day). Cardiac function evaluation was carried out using echocardiography. Histological examinations, including hematoxylin and eosin (HE) staining, Masson staining, and immunohistochemistry studies, were conducted 90 days after the occurrence of MI. Additionally, Western blotting was employed to assess TGF‐β1, p-Smad2, and p-Smad3 levels.ResultsThe administration of icariin revealed a noteworthy enhancement in cardiac function among rats afflicted with left anterior descending coronary artery (LAD) ligation. In comparison to the icariin groups, the MI group exhibited reduced EF and FS, along with elevated LVEDD and LVESD. Furthermore, the cardiac fibrosis levels in the MI group rats exhibited a considerable increase compared to those in the icariin group. Notably, the levels of Collagen I, Collagen III, MMP2, and MMP9 were significantly higher in the MI group than in the icariin group, with evident distinctions. Moreover, the expression levels of TGF-β, IL-13, p-Smad2, and p-Smad3 were notably upregulated in the MI group compared to the icariin group.ConclusionsIn an experimental rat model of MI, the administration of icariin resulted in the amelioration of both cardiac function and remodeling processes, operating through the intricate TGF-β1/Smad signaling pathway.

Veno-Venous Coiling as A Strategy to Wean Extracorporeal Membrane Oxygenator Post Adult Fontan Completion

We discuss a case of veno-venous collaterals in a patient with Fontan circulation post complex redo-surgery, which impeded veno-venous extracorporeal membrane oxygenation (VV-ECMO) weaning. A 31-year-old male, born with complex congenital heart disease (D-transposition of the great vessels, tricuspid atresia, aortic coarctation, ventricular septal defect, and hypoplastic right ventricle) with single ventricle physiology. The patient underwent multiple cardiac surgeries leading to Fontan completion. He subsequently developed significant aortic regurgitation with progressive left ventricular dilatation requiring multiple readmissions for congestive heart failure. Despite maximal medical optimisation he remained symptomatic and was offered further surgery. Complex 6th redo-operation with aortic valve replacement, modification to intracardiac fenestrated Fontan and insertion of intra-aortic balloon pump was performed. At 72 hours postoperative, VV-ECMO was required for refractory hypoxia. Right heart catheterisation was performed with coiling of two large fistulous venous connections. Post-coiling saturations improved from 92% to 98%. The patient was successfully weaned from VV-ECMO and decannulated the following day. This case demonstrates successful embolisation for veno-venous collaterals causing significant right to left shunt and hypoxia, in a patient with Fontan circulation.