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Circulation Research Sep 2023Cardiac valve disease is observed in 2.5% of the general population and 10% of the elderly people. Effective pharmacological treatments are currently not available, and...
BACKGROUND
Cardiac valve disease is observed in 2.5% of the general population and 10% of the elderly people. Effective pharmacological treatments are currently not available, and patients with severe cardiac valve disease require surgery. PROX1 (prospero-related homeobox transcription factor 1) and FOXC2 (Forkhead box C2 transcription factor) are transcription factors that are required for the development of lymphatic and venous valves. We found that PROX1 and FOXC2 are expressed in a subset of valvular endothelial cells (VECs) that are located on the downstream (fibrosa) side of cardiac valves. Whether PROX1 and FOXC2 regulate cardiac valve development and disease is not known.
METHODS
We used histology, electron microscopy, and echocardiography to investigate the structure and functioning of heart valves from mice in which was conditionally deleted from VECs. Isolated valve endothelial cells and valve interstitial cells were used to identify the molecular mechanisms in vitro, which were tested in vivo by RNAScope, additional mouse models, and pharmacological approaches. The significance of our findings was tested by evaluation of human samples of mitral valve prolapse and aortic valve insufficiency.
RESULTS
Histological analysis revealed that the aortic and mitral valves of mice become progressively thick and myxomatous. Echocardiography revealed that the aortic valves of mice are stenotic was downregulated and PDGF-B (platelet-derived growth factor-B) was upregulated in the VECs of mice. Conditional knockdown of FOXC2 and conditional overexpression of PDGF-B in VECs recapitulated the phenotype of mice. PDGF-B was also increased in mice lacking FOXC2 and in human mitral valve prolapse and insufficient aortic valve samples. Pharmacological inhibition of PDGF-B signaling with imatinib partially ameliorated the valve defects of mice.
CONCLUSIONS
PROX1 antagonizes PDGF-B signaling partially via FOXC2 to maintain the extracellular matrix composition and prevent myxomatous degeneration of cardiac valves.
Topics: Animals; Humans; Mice; Endothelial Cells; Heart Valve Diseases; Mitral Valve; Mitral Valve Prolapse; Transcription Factors; Proto-Oncogene Proteins c-sis
PubMed: 37555328
DOI: 10.1161/CIRCRESAHA.123.323027 -
Biology of Sex Differences Jul 2023Chronic kidney disease (CKD) is linked to an increased cardiovascular disease (CVD) burden. Albeit underappreciated, sex differences are evident in CKD with females...
BACKGROUND
Chronic kidney disease (CKD) is linked to an increased cardiovascular disease (CVD) burden. Albeit underappreciated, sex differences are evident in CKD with females being more prone to CKD development, but males progressing more rapidly to kidney failure (KF). Cardiovascular remodelling is a hallmark of CKD with increased arterial and valvular calcification contributing to CKD. However, little is known regarding sex differences in calcific cardiovascular remodelling in KF patients. Thus, we hypothesise that sex differences are present in coronary artery calcification (CAC) and aortic valve calcification (AVC) in patients with KF.
METHODS
KF patients, males (n = 214) and females (n = 107), that had undergone computer tomography (CT) assessment for CAC and AVC were selected from three CKD cohorts. All patients underwent non-contrast multi-detector cardiac CT scanning, with CAC and AVC scoring based on the Agatston method. Baseline biochemical measurements were retrieved from cohort databases, including plasma analyses for inflammation markers (IL-6, TNF, hsCRP) and oxidative stress by skin autofluorescence measuring advanced glycation end-products (AGE), amongst other variables.
RESULTS
Sex-disaggregated analyses revealed that CAC score was associated with age in both males and females (both p < 0.001). Age-adjusted analyses revealed that in males CAC was associated with diabetes mellitus (DM) (p = 0.018) and CVD (p = 0.011). Additionally, for females CAC associated with IL-6 (p = 0.005) and TNF (p = 0.004). In both females and males CAC associated with AGE (p = 0.042 and p = 0.05, respectively). CAC was associated with mortality for females (p = 0.015) independent of age. AVC in females was not reviewed due to low AVC-positive samples (n = 14). In males, in multivariable regression AVC was associated with age (p < 0.001) and inflammation, as measured by IL-6 (p = 0.010).
CONCLUSIONS
In female KF patients inflammatory burden and oxidative stress were associated with CAC. Whereas in male KF patients oxidative stress and inflammation were associated with CAC and AVC, respectively. Our findings suggest a sex-specific biomarker signature for cardiovascular calcification that may affect the development of cardiovascular complications in males and females with KF.
Topics: Humans; Female; Male; Aortic Valve; Heart Valve Diseases; Interleukin-6; Coronary Artery Disease; Renal Insufficiency, Chronic; Inflammation; Renal Insufficiency
PubMed: 37443048
DOI: 10.1186/s13293-023-00530-x -
Journal of the American College of... Sep 2023The usefulness of aortic valve sparing operations to treat aortic root aneurysm in patients with Marfan syndrome (MS) remains controversial.
BACKGROUND
The usefulness of aortic valve sparing operations to treat aortic root aneurysm in patients with Marfan syndrome (MS) remains controversial.
OBJECTIVES
The purpose of this study was to evaluate the occurrence of cardiovascular events in patients with MS who have undergone valve-preserving aortic root replacement.
METHODS
Patients with MS who had aortic valve sparing operations (reimplantation of the aortic valve or remodeling of the aortic root) from 1988 through 2019 were followed prospectively for a median of 14 years. Pertinent data from clinical, echocardiographic, computed tomography, and magnetic resonance images of the aorta were collected and analyzed.
RESULTS
There were 189 patients whose mean age was 36 years, and 67% were men. Ten patients presented with acute type A dissection and 29 had mitral regurgitation. There were 52 patients at risk at 20 years. Mortality rate at 20 years was 21.5% (95% CI: 14.7%-30.8%); advancing age and preoperative aortic dissections were associated with increased risk of death by multivariable analysis. At 20 years, the cumulative incidence of moderate or severe aortic insufficiency was 14.5% (95% CI: 9.5%-22.0%), reoperation on the aortic valve was 7.5% (95% CI: 3.9%-14.7%), and new distal aortic dissections was 19.9% (95% CI: 13.9%-28.5%). Remodeling of aortic root was associated with greater risk of developing aortic insufficiency and aortic valve reoperation than reimplantation of the aortic valve.
CONCLUSIONS
Aortic valve sparing operations provide stable aortic valve function and low rates of valve-related complications during the first 2 decades of follow-up but aortic dissections remain problematic in patients with MS.
Topics: Male; Humans; Adult; Female; Marfan Syndrome; Aorta, Thoracic; Aorta; Aortic Dissection; Aortic Valve Insufficiency
PubMed: 37673508
DOI: 10.1016/j.jacc.2023.06.032 -
Annals of Cardiothoracic Surgery Jul 2023
PubMed: 37554713
DOI: 10.21037/acs-2023-avs2-14 -
Brazilian Journal of Cardiovascular... Oct 2023Aortic stenosis (AS) is the most common valvular heart disease and the most common indication for aortic valve replacement in adults. Aortic valve neocuspidization...
INTRODUCTION
Aortic stenosis (AS) is the most common valvular heart disease and the most common indication for aortic valve replacement in adults. Aortic valve neocuspidization (AVNeo) with fixed autologous pericardium, also known as the Ozaki procedure, is a possible alternative treatment of AS. Autopericardial valves save the dynamics and physiological anatomy of the aortic root, however, the service life of autopericardial leaflets is limited. There is no data about factors that may influence the development of AVNeo insufficiency. Here, we assessed the effect of autopericardial leaflet symmetry on the development of aortic insufficiency after Ozaki procedure.
METHODS
This study included 381 patients with AS who underwent Ozaki procedure. Patients were divided into group 1 (171 patients with symmetric aortic root) and group 2 (210 patients with asymmetric aortic root).
RESULTS
The maximum observation period was up to 65 months. Sixteen cases of aortic insufficiency were detected in group 1, and 33 cases were detected in group 2. Based on the results of Cox regression, the predictors of aortic insufficiency in the late postoperative period are age and asymmetry of neocusps. According to results of Kaplan-Meier analysis, insufficiency of AVNeo in the maximum follow-up period after surgical correction of AS for group 1 patients was significantly lower than for group 2 patients (P=0.006).
CONCLUSION
Asymmetric neocusps increase the risk of aortic insufficiency in the mid-term period after Ozaki procedure. And the older the patients at the time of surgery, the less likely they develop AVNeo insufficiency.
Topics: Adult; Humans; Aortic Valve; Heart Valve Diseases; Aortic Valve Stenosis; Aortic Valve Insufficiency; Heart Valve Prosthesis; Pericardium; Treatment Outcome
PubMed: 37797236
DOI: 10.21470/1678-9741-2022-0370 -
Nature Genetics Feb 2024Cardiac blood flow is a critical determinant of human health. However, the definition of its genetic architecture is limited by the technical challenge of capturing...
Cardiac blood flow is a critical determinant of human health. However, the definition of its genetic architecture is limited by the technical challenge of capturing dynamic flow volumes from cardiac imaging at scale. We present DeepFlow, a deep-learning system to extract cardiac flow and volumes from phase-contrast cardiac magnetic resonance imaging. A mixed-linear model applied to 37,653 individuals from the UK Biobank reveals genome-wide significant associations across cardiac dynamic flow volumes spanning from aortic forward velocity to aortic regurgitation fraction. Mendelian randomization reveals a causal role for aortic root size in aortic valve regurgitation. Among the most significant contributing variants, localizing genes (near ELN, PRDM6 and ADAMTS7) are implicated in connective tissue and blood pressure pathways. Here we show that DeepFlow cardiac flow phenotyping at scale, combined with genotyping data, reinforces the contribution of connective tissue genes, blood pressure and root size to aortic valve function.
Topics: Humans; Blood Flow Velocity; Aorta; Magnetic Resonance Imaging; Aortic Valve Insufficiency; Aortic Valve
PubMed: 38082205
DOI: 10.1038/s41588-023-01587-5 -
JACC. Cardiovascular Interventions Aug 2023Patients with severe aortic regurgitation (AR) are often not considered for surgery because of increased surgical risk. Because of unique anatomical characteristics...
BACKGROUND
Patients with severe aortic regurgitation (AR) are often not considered for surgery because of increased surgical risk. Because of unique anatomical characteristics among patients with AR, interventional treatment options are limited, and implantation results are inconsistent compared with those among patients with aortic stenosis.
OBJECTIVES
The authors describe the initial commercial experience of the first Conformité Européenne-marked transfemoral transcatheter aortic valve replacement system (JenaValve Trilogy [JV]) for the treatment of patients with AR.
METHODS
This multicenter registry included 58 consecutive patients from 6 centers across Germany. Transcatheter aortic valve replacement was performed with the JV system for isolated severe and symptomatic AR. Patient characteristics, primary implantation outcomes, and valve performance up to 30 days were analyzed using Valve Academic Research Consortium 3 definitions.
RESULTS
The mean patient age was 76.5 ± 9 years, with a mean Society of Thoracic Surgeons score of 4.2% ± 4.3%. Device success was achieved in 98% of patients. The mean gradient was 4.3 ± 1.6 mm Hg, and no moderate or severe paravalvular regurgitation occurred. No conversion to open heart surgery or valve embolization was reported. There were no major vascular complications or bleeding events. The rate of new permanent pacemaker implantation was 19.6%. At 30 days, 92% of the patients were in NYHA functional class I or II, and the 30-day mortality rate was 1.7%.
CONCLUSIONS
Treatment of patients with severe symptomatic AR using the transfemoral JV system is safe and effective. Given its favorable hemodynamic performance and low complication rates, this system may offer a new treatment option for patients with AR not suitable for surgery.
Topics: Humans; Aged; Aged, 80 and over; Aortic Valve Insufficiency; Transcatheter Aortic Valve Replacement; Treatment Outcome; Heart; Aortic Valve Stenosis
PubMed: 37648344
DOI: 10.1016/j.jcin.2023.07.038 -
JACC. Cardiovascular Interventions Aug 2023
Topics: Humans; Transcatheter Aortic Valve Replacement; Aortic Valve Insufficiency; Treatment Outcome
PubMed: 37648343
DOI: 10.1016/j.jcin.2023.07.018 -
Medical Science Monitor : International... Feb 2024Aortic root aneurysms are one of the most common aortic root diseases, involving the aortic valve, aortic sinus, bilateral coronary arteries, and part of the ascending... (Review)
Review
Aortic root aneurysms are one of the most common aortic root diseases, involving the aortic valve, aortic sinus, bilateral coronary arteries, and part of the ascending aorta. It is a life-threatening aortic disease with a high mortality rate of approximately 90%, due to aortic aneurysm rupture. Aortic valve insufficiency is one of the most common complications of aortic root aneurysms that can lead to acute left heart failure. The etiology of aortic root aneurysms is not yet completely clear and is mainly related to genetic diseases, such as Marfan syndrome and atherosclerosis. It can also occur secondary to aortic valve stenosis or a bivalve deformity. Surgery is the primary treatment for aortic root aneurysms, and aortic root replacement is a classic surgical method. However, the incidences of perioperative complications and mortality are relatively high, particularly in high-risk patients. In recent years, the anatomical structure of the aortic root has been gradually refined, and an in-depth understanding of root aneurysms has led to individualized treatment methods. Conservative drug therapy (ß-receptor blockers, angiotensin-converting enzyme inhibitors, or angiotensin receptor blockers), Bentall and modified Bentall surgeries (Button technology, Cabrol surgery, and modified Cabrol surgery), valve-sparing aortic root replacement (David and Yacoub), personalized external aortic root support, and endovascular intervention therapy have significantly improved the perioperative and long-term survival rates of patients with aortic root aneurysms. However, different treatment methods have their own advantages and disadvantages. This review aimed to summarize the current research progress and treatment of aortic root aneurysms.
Topics: Humans; Aortic Root Aneurysm; Aorta; Aortic Aneurysm, Thoracic; Marfan Syndrome; Aortic Valve Insufficiency; Aortic Valve; Aortic Diseases; Treatment Outcome
PubMed: 38332569
DOI: 10.12659/MSM.943216 -
The Journal of Veterinary Medical... Sep 2023A 1-month-old crossbred calf was referred for examination due to marked systolic heart murmurs and poor growth. The heart murmur was most audible on the right side of...
A 1-month-old crossbred calf was referred for examination due to marked systolic heart murmurs and poor growth. The heart murmur was most audible on the right side of the cranial thorax. Cardiomegaly was evident on chest radiography, and echocardiography demonstrated aortic regurgitation and decreased fractional shortening. Cardiomegaly, aortic root dilation and cardiac displacement were confirmed by computed tomography. At necropsy, the heart was enlarged, and all three aortic valve leaflets were irregularly shaped. In calves with chronic aortic insufficiency, remodeling displacement of the heart and aorta causes changes in the location and timing of heart murmurs. Therefore, aortic insufficiency cannot be ruled out when a systolic heart murmur can be observed in the right chest wall.
Topics: Animals; Cattle; Aortic Valve Insufficiency; Aortic Valve; Heart Murmurs; Echocardiography; Cardiomegaly; Cattle Diseases
PubMed: 37532587
DOI: 10.1292/jvms.23-0139