Progressive Aortic Root Dilatation Research Articles

NON- DISSECTING LARGE AORTIC ARCH ANEURYSM LEADING TO CHRONIC AORTIC INSUFFICIENCY PRESENTING AS ACUTE HEART FAILURE REVEALING MARFAN SYNDROME

Introduction: Marfan syndrome is an autosomal dominant disorder of connective tissue which has many clinical symptoms and whose prognosis depends on associated cardiovascular complications, dominated by progressive aortic root dilation, which may lead to aortic dissection, rupture or aortic regurgitation. Prevention of these life threatening complications is of major importance. Case presentation: We report here a case of a 42-year-old man, with a history of two retinal detachments in 2015 and 2018, who presented with severe aortic valve regurgitation and severe heart failure secondary to significant aortic root dilatation revealing Marfan syndrome. Unfortunately, before referring the patient to the surgeon, the patient ended up dying from an unrecovered cardiac arrest. Conclusion: It is very important to recognize Marfan syndrome on time and the preventive actions should be undertaken in order to avoid life-threatening consequences of this disorder. Echocardiography and especially the angioscanner represent the main tools used for the diagnosis of gravity and the follow-up of this condition.

Smooth Muscle Cell Klf4 Expression Is Not Required for Phenotype Modulation or Aneurysm Formation in Marfan Syndrome Mice-Brief Report.

Smooth muscle cell (SMC) phenotypic reprogramming toward a mixed synthetic-proteolytic state is a central feature of aortic root aneurysm in Marfan syndrome (MFS). Previous work identified Klf4 as a potential mediator of SMC plasticity in MFS. MFS (Fbn1C1041G/+) mouse strains with an inducible vascular SMC fluorescent reporter (MFSSMC) with or without SMC-specific deletion of Klf4 exons 2 to 3 (MFSSMC-Klf4Δ) were generated. Simultaneous SMC tracing and Klf4 loss-of-function (Klf4Δ mice) was induced at 6 weeks of age. Aneurysm growth was assessed via serial echocardiography (4-24 weeks). Twenty-four-week-old mice were assessed via histology, RNA in situ hybridization, and aortic single-cell RNA sequencing. MFS mice demonstrated progressive aortic root dilatation compared with control (WTSMC) mice regardless of Klf4 genotype (P<0.001), but there was no difference in aneurysm growth in MFSSMC-Klf4Δ versus MFSSMC (P=0.884). Efficient SMC Klf4 deletion was confirmed via lineage-stratified genotyping, RNA in situ hybridization, and immunohistochemistry. Single-cell RNA sequencing of traced SMCs revealed a highly similar pattern of phenotype modulation marked by loss of contractile markers (eg, Myh11, Cnn1) and heightened expression of matrix genes (eg, Col1a1, Fn1) between Klf4 genotypes. Pseudotemporal quantitation of SMC dedifferentiation confirmed that Klf4 deletion did not alter the global extent of phenotype modulation, but reduced expression of 23 genes during this phenotype transition in MFSSMC-Klf4Δmice, including multiple chondrogenic genes expressed by only the most severely dedifferentiated SMCs (eg, Cytl1, Tnfrsf11b). Klf4 is not required to initiate SMC phenotype modulation in MFS aneurysm but may exert regulatory control over chondrogenic genes expressed in highly dedifferentiated SMCs.

Cardiac function in adolescents and young adults with 22q11.2 deletion syndrome without congenital heart disease

BackgroundDiagnosis and treatment of 22q11.2 deletion syndrome (22q11.2DS) have led to improved life expectancy and achievement of adulthood. Limited data on long-term outcomes reported an increased risk of premature death for cardiovascular causes, even without congenital heart disease (CHD). The aim of this study was to assess the cardiac function in adolescents and young adults with 22q11.2DS without CHDs. MethodsA total of 32 patients (20M, 12F; mean age 26.00 ± 8.08 years) and a healthy control group underwent transthoracic echocardiography, including Tissue Doppler Imaging (TDI) and 2-dimensional Speckle Tracking Echocardiography (2D-STE). ResultsCompared to controls, 22q11.2DS patients showed a significant increase of the left ventricle (LV) diastolic and systolic diameters (p = 0.029 and p = 0.035 respectively), interventricular septum thickness (p = 0.005), LV mass index (p < 0.001) and aortic root size (p < 0.001). 2D-STE analysis revealed a significant reduction of LV global longitudinal strain (p < 0.001) in 22q11.2DS than controls. Moreover, several LV diastolic parameters were significantly different between groups. ConclusionsOur results suggest that an echocardiographic follow-up in 22q11.2DS patients without CHDs can help to identify subclinical impairment of the LV and evaluate a potential progression of aortic root dilation over time, improving outcomes, reducing long-term complications and allowing for a better prognosis.

The Surgical Strategy for Progressive Dilatation of Aortic Root and Aortic Regurgitation After Repaired Tetralogy of Fallot: A Case Report

It has been found that postoperative progressive dilatation of aortic root is not rare for adult patients with repaired Tetralogy of Fallot (TOF), which leads to severe aortic regurgitation or even fatal dissection. Therefore, clinically, surgical treatment for both regurgitated aortic valve and dilated root is needed based on preoperative assessments and individual treatment strategies.

Effect of the General Inhibitor of Nitric Oxide Synthase (L‐NAME) On Cardiac and Aortic Function and Structure in A Mouse Model of Marfan Syndrome‐Associated Aortic Aneurysm

Marfan Syndrome (MFS) is an autosomal‐dominant connective tissue disorder caused by missense mutations in the gene that encodes for Fibrillin‐1 (FBN1). FBN1 is an extracellular matrix glycoprotein that functions as a scaffolding protein during the formation and maturation of elastic fibers. The mechanism underlying MFS pathogenesis stems from a crosstalk between the Angiotensin‐II pathway and over activation of transforming growth factor‐beta signaling. There are several clinical manifestations seen in MFS, but the most serious and life‐threatening is the aortic aneurysm due to degradation and fragmentation of aortic wall elastin fibers. If left untreated, aortic aneurysm progression may lead to dissection and rupture.Previous studies in the MFS mouse model have shown that the progression of aortic aneurysm is associated with a significant decline in endothelial function and nitric oxide (NO) production in the aortic wall, and that overexpression of endothelial nitric oxide synthase (eNOS) could delay the progression of aortic root aneurysm in MFS mice. A recent study in our lab has also shown that mild aerobic exercise can block aortic aneurysm in MFS mice. It is well established that exercise can improve endothelial function mainly through an increase in eNOS‐mediated NO production. Therefore, we tested the hypothesis that mild aerobic exercise prevents aortic aneurysm progression in the mouse model of MFS mainly through increasing the production of NO within the aortic wall.To test this hypothesis, C57BL/6 WT and MFS mice were subjected to daily treadmill exercise (at 55% of VO2max, starting at 4 weeks of age) in the absence or presence of the general inhibitor of NO production, N(G)‐Nitro‐L‐arginine methyl ester (L‐NAME) at 0.05 g per 100 mL of drinking water. At 6‐months of age, in vivo imaging of the aortic root diameter and pulse wave velocity (PWV) as an index of wall stiffness, was performed using a high‐resolution Vevo2100 ultrasound system. The aortic root diameter at the sinus of Valsalva, and pulse wave velocity were both increased in MFS mice compared to WT, however MFS mice subjected to treadmill exercise had significantly decreased aortic root diameter and pulse wave velocity compared to sedentary MFS mice. In situ analysis of aortic wall integrity was analyzed at 6 months by Van Geison staining. Our results revealed that MFS mice had an increase in elastin fragment count and a decrease in elastin fiber length compared to WT. Interestingly, MFS mice subjected to exercise had fewer elastin fragment count and an increase in elastin fiber length compared to sedentary MFS mice. Interestingly, L‐NAME treatment reversed the protective effects of exercise on aortic root diameter and pulse wave velocity in MFS mice to a level that was not different than MFS sedentary groups. This study provides preliminary evidence that mild aerobic exercise blocks the progression of aortic root dilation in MFS mice through increasing the production of NO within the aortic wall, and further emphasizes the value of increased physical activity in aneurysm population.

Is there a role for angiotensin II–receptor blockers for ascending aorta dilatation in pediatric patients with normally functioning bicuspid aortic valve?

BackgroundCurrently there are no data regarding medical therapy of aortic dilatation in pediatric patients with normally functioning bicuspid aortic valve (BAV). Aim of the study was to describe the rates of change of aortic root diameters in untreated pediatric patients with normally functioning BAV and in patients with documented progressive dilatation treated with medical therapy. MethodsRetrospective analysis performed on 191 pediatric patients with normally functioning BAV followed from 2005 to 2021 with serial examinations. ResultsAortic root dilatation was observed in 46.3% of patients, was mainly localized at the proximal ascending aorta and judged mild. After a mean follow-up of 3.7 ± 2.7 years among 175 untreated patients 52.6% presented a new onset or progressive aortic root dilatation (“progressive”) while 47.4% presented normal and stable aortic diameters. Eight percent of untreated patients with a mild aortic dilatation at baseline presented a normalization of aortic diameters. “Progressive” patients presented more frequently a BAV with a raphe (73.9% vs 57.8%, p = .037) and a mild aortic regurgitation (76% vs 45.8%, p = .00007). Thirty “progressive” patients were treated with medical therapy. After a mean follow-up of 3.3 ± 2.3 years no significant differences were observed between aortic root z score progression in “stable”, “progressive” and “treated” patients. ConclusionsIn a small cohort of patients with normally functioning BAV a raphe and a mild regurgitation are common in progressive aortic dilatation. Medical therapy didn't affect aortic dilatation in patients with progressive and mild dilatation. A randomized controlled trial is needed.

Magnetic resonance angiography derived predictors of progressive dilatation and surgery of the aortic root in Marfan syndrome.

BackgroundTo identify magnetic resonance (MR) angiography derived predictors of progressive dilatation and surgery of the aortic root in Marfan syndrome.Material and methodsWe retrospectively included 111 patients (32.7±16.5 years, range: 7–75 years) with a total of 446 MR angiographies. Aortic diameter growth rates of the entire thoracic aorta and Z-scores were estimated from annual diameter measurements. Aortic root shape was subdivided into three different types: (T0) normal; (T1) localized dilatation; (T2) generalized aortic root dilatation. Aortic diameter, Z-score, age, and aortic root shape at baseline were tested as predictors of aortic root dilatation using a multivariate logistic regression model.ResultsThe highest aortic growth rate was observed at the level of the sinuses of Valsalva. Higher aortic root diameters and Z-scores at baseline predicted an increased growth of the aortic root (p = 0.003 and p<0.001). Young age (<30 years) was a predictor for the increase of Z-scores when compared to patients ≥30 years (p = 0.019). 25/111 patients (22.5%) had a T0 aortic root shape, 59/111 patients (53.2%) had a T1 aortic root shape, and 27/111 patients (24.3%) had a T2 aortic root shape. Aortic root shape did not predict further aortic growth (p>0.05). However, significantly more patients undergoing surgery had a generalized aortic dilatation (19/28, 76.9%) than a localized aortic root dilatation (9/28, 32.1%) (p = 0.001).ConclusionLarger baseline aortic root diameter and Z-score as well as young age predict solely progressive aortic root dilatation in Marfan patients. MR angiography derived type of aortic root shape does not predict aortic growth, but patients with generalized aortic root dilatation are referred more frequently for aortic surgery.

Concomitant valve-sparing aortic root replacement with tetralogy of Fallot repair in a 30-year-old patient: A case report.

Introduction and importanceAortic regurgitation and aortic root dilatation are common features in adults with both repaired and unrepaired tetralogy of Fallot (TOF). Valve-sparing aortic root replacement (VSARR) is an effective repair for aortic regurgitation due to progressive aortic root dilatation with TOF after repair. However, the effectiveness of this technique for unrepaired patients has rarely been reported.Case presentationWe reported a case of a 30-year-old man with cyanosis and exertional dyspnea. Echocardiography and computed tomography showed unrepaired TOF with significant aortic regurgitation and massively dilated aortic root. Aortic root replacement was mandatory. He underwent successful concomitant VSARR with TOF repair. At 6-month follow-up, he remains stable with trivial aortic regurgitation on echocardiogram.Clinical discussionIn unrepaired TOF, the absence of sub-annular muscular rim and the unbalance of aortic sinuses make VSARR utmost challenging. If can be done successfully, VSARR preserves the native aortic valve and avoids lifelong anticoagulation therapy.ConclusionConcomitant VSARR with TOF repair can be safely and effectively applied for unrepaired patients presenting with progressive aortic root dilatation and significant aortic regurgitation.

Long-term follow-up of a patient with JAG1-associated retinopathy

To report the long-term structural and functional changes in the posterior segments of an adult with an unusual retinal dystrophy caused by a novel mutation in JAG1. A 33-year-old female underwent comprehensive ophthalmic examination, including best corrected visual acuity (BCVA) measurement, dilated fundus imaging (wide-angle fundus colour and short wavelength autofluorescence imaging), macular and peripheral spectral-domain optical coherence tomography (SD-OCT) and electroretinography (ERG) at baseline and 10years later at the age of 43. The patient also underwent systemic review with detailed cardiac, brain and renal investigations. During follow-up, genetic analysis using whole-exome sequencing was performed on the patient and her parents to identify disease-causing variants. The patient's main complaint was of a recent onset of bilateral photophobia and blurred vision in the left eye. On examination, the most striking retinal finding was of bilateral well-demarcated, anterior circumferential chorioretinal atrophy with scattered pigment clumping from the mid periphery to the ora. In addition, she had posterior pole RPE hypopigmentation, peripapillary chorioretinal atrophy, left macular choroidal folds and retinal vasculature tortuosity with atypical branching. Her retinal electrophysiology was consistent with a cone rod photoreceptor dystrophy and left macular dysfunction. Ten years later, her BCVA, the anterior circumferential chorioretinal atrophy and her visual field constriction all remained stable. Her retinal electrophysiology demonstrated deterioration of left rod function, while cone dysfunction remained stable. Macular function deteriorated in both eyes. During follow-up, she was also noted to have progressive aortic root dilatation, posterior embryotoxon and an x ray diagnosis of butterfly vertebrae. Whole-exome sequencing revealed a novel c.2412C > A p.(Tyr804Ter) truncating mutation in JAG1 that was predicted to be pathogenic and suggested a diagnosis of Alagille syndrome. This is the first report of the long-term detailed follow-up of a patient with Alagille syndrome whose most striking ophthalmic finding was bilateral well-demarcated, anterior circumferential chorioretinal atrophy. During follow-up, this finding remained stable, suggesting that this may be developmental in origin. This is in contrast with the progressive deterioration in the posterior pole retinal and macular function.

In silico study of the ageing effect upon aortic valves

A fluid–structure interaction (FSI) numerical model of the aortic valve was used to simulate and compare young and physiological aged operating conditions. The effect of normal ageing was considered by introducing alterations typically associated with senility: namely mild stiffening of the tissues and progressive dilation of the aortic chamber. The aim of this study is to provide a haemodynamic baseline which allows to assess the typical physiological variations associated with advancing age. Results were analysed in terms of leaflets kinematics, flow dynamics, pressure and valve performance parameters. The study indicates that the normal changes occurring with ageing, such as stiffening and progressive aortic root dilation, can result in substantial alterations in the haemodynamics and mechanical efficiency of the aortic valve. In particular, mild tissue stiffening and aortic root dilation reduce the valve efficiency over the cardiac cycle. The concomitant presence of both phenomena can lead to some mitigation of the impairment. The observed changes, which can be associated with normal and healthy ageing, need to be taken into consideration when evaluating the real pathological contribution of aortic valve diseases occurring in aged patients.

Aortic root longitudinal strain by speckle-tracking echocardiography predicts progressive aortic root dilation in Marfan syndrome patients

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Spanish Ministry of Science, Innovation and Universities; Instituto de Salud Carlos III Introduction In Marfan syndrome (MFS) patients reduced longitudinal strain of the ascending aorta (AAo) as measured by applying feature-tracking on cine cardiac magnetic resonance (CMR) images predicts aortic root dilation and aortic events during the follow-up. Speckle-tracking is well established for cardiac deformation assessment but proximal aorta applications are challenging due to limited wall thickness and substantial cardiac motion. Moreover, echocardiography is widely used in the clinical assessment aortic diseases. Purpose We aimed to test a speckle-tracking tool for root longitudinal strain analysis in terms of comparison with CMR-derived AAo longitudinal strain and reproducibility and as predictor of dilation in MFS patients. Methods Thirty-five MFS patients diagnosed by original GHENT criteria, with maximum aortic root diameter of 45 mm and free from previous aortic dissection or cardiac/aortic surgery and non-severe aortic regurgitation were consecutive enrolled and followed-up. CMR and echocardiography were performed less than 2 months apart. Baseline and final aortic root diameter were measured on CMR images. To quantify aortic root cyclic elongation by echocardiography, two regions of interests were manually created covering both walls in a parasternal long-axis view and tracked along the cardiac cycle (Figure 1). Longitudinal strain was computed as the average of maximum increase in relative distance of several sub-regions covering both walls. CMR-derived AAo longitudinal strain was available in 29 patients. Intra-observer reproducibility was tested in 15 patients via intraclass correlation coefficient (ICC) for single-rater absolute agreement. Results Aortic root longitudinal strain by echocardiography was mildly related to CMR-derived AAo longitudinal strain (R = 0.27) and was larger compared to CMR-derived values (16.2 ± 6.0 vs 11.3 ± 4.3). Reproducibility was high, with ICC of 0.811, R = 0.802, p &amp;lt; 0.001. After a mean follow up of 76 ± 13 months, aortic root diameter grew in 20 patients with a rate of 0.29± 0.24 mm/year. Overall mean growth-rate was 0.87 ± 0.33 mm/year. In multivariable analysis corrected for age and baseline aortic root diameter, baseline longitudinal strain by echocardiography was independently and inversely related to progressive dilation (p = 0.033). Conclusions The measurement of aortic root longitudinal strain by speckle-tracking echocardiography is feasible. Aortic root longitudinal strain is an independent predictor of progressive dilation in MFS patients. This may permit the improvement of risk-stratification in aortic diseases in large scale studies. Abstract Figure 1

Aortic Root Dilatation in Taiwanese Patients with Mucopolysaccharidoses and the Long-Term Effects of Enzyme Replacement Therapy.

Background: Cardiovascular abnormalities have been observed in patients with mucopolysaccharidosis (MPS) of any type, with the most documented abnormalities being valvular regurgitation and stenosis and cardiac hypertrophy. Only a few studies have focused on aortic root dilatation and the long-term effects of enzyme replacement therapy (ERT) in these patients. Methods: We reviewed echocardiograms of 125 Taiwanese MPS patients (age range, 0.1 to 19.1 years; 11 with MPS I, 49 with MPS II, 25 with MPS III, 29 with MPS IVA, and 11 with MPS VI). The aortic root diameter was measured at the sinus of Valsalva. Results: Aortic root dilatation (z score >2) was observed in 47% of the MPS patients, including 66% of MPS IV, 51% of MPS II, 45% of MPS VI, 28% of MPS III, and 27% of MPS I patients. The mean aortic root diameter z score was 2.14 (n = 125). The patients with MPS IV had the most severe aortic root dilatation with a mean aortic root diameter z score of 3.03, followed by MPS II (2.12), MPS VI (2.06), MPS III (1.68), and MPS I (1.03). The aortic root diameter z score was positively correlated with increasing age (n = 125, p < 0.01). For the patients with MPS II, III, and IV, aortic root diameter z score was also positively correlated with increasing age (p < 0.01). For 16 patients who had received ERT and had follow-up echocardiographic data (range 2.0–16.2 years), the mean aortic root diameter z score change was −0.46 compared to baseline (baseline 2.49 versus follow-up 2.03, p = 0.490). Conclusions: Aortic root dilatation was common in the patients with all types of MPS, with the most severe aortic root dilatation observed in those with MPS IV. The severity of aortic root dilatation worsened with increasing age, reinforcing the concept of the progressive nature of this disease. ERT for MPS appears to stabilize the progression of aortic root dilatation.

Postoperatif Fallot Tetralojili Çocuklarda Aort Kökü Dilatasyonu, Kısa ve Orta Dönem Sonuçlarımız

Amaç: Tam düzeltme ameliyatı yapılmış Fallot tetralojili hastalarımızın klinik durumlarının değerlendirilmesi, ritim bozukluklarının araştırılması, ekokardiyografi ile ventrikül fonksiyonlarının ve aort kökü dilatasyonunun değerlendirilmesidir. Gereç ve Yöntemler: İstanbul Üniversitesi, İstanbul Tıp Fakültesi Çocuk Kardiyoloji bölümünde izlenen, düzeltme operasyonu uygulanmış Fallot tetralojili 50 çocuk çalışmaya dahil edildi. Düzeltilmiş Fallot tetralojili olgular aort kökü dilate olanlar ve dilate olmayanlar diye iki guruba ayrıldı. Her iki gurup arasında cinsiyet, tam düzeltme operasyonu yaşı, aort yetersizliği, triküspit yetersizliği, pulmoner yetersizlik, palyatif tedavi ve transanüler yama kullanımı açısından farklar değerlendirildi. Pulmoner kapak yetmezliği, tam düzeltme ameliyatı sırasında uygulanan transanüler yama yapılanlar ve yapılmayanlar olarak karşılaştırıldı. Düzeltilmiş Fallot tetralojili olguların ekokardiyografik olarak ölçülen aort kökü ve asendan aort çapları yaş, cinsiyet ve vücut yüzey alanlarına göre normal dağılımları ile değerlendirildi. Bulgular: Çalışmaya 24 Ocak-15 Mayıs 2014 tarihleri arasında 50 olgu alındı. Çalışmaya katılan olguların yaşları 2-21 yıl arasında değişmekte olup, ortalama 9.9 ±4.5 yıldır. Çalışmaya katılanların %52’si (n=26) erkek, %48’i (n=24) kızdır. Olguların total düzeltme yaşları 6 (0.5 yıl) ile 190 (15.8 yıl) ay arasında değişmekte olup, ortalama 28.3 ± 28.3 (2.3 ± 2.3 yıl) aydır. Postoperatif süreleri 1.3-17.8 yıl arasında değişmekte olup, ortalama 8.0 ± 4.1 yıldır. Olguların %28’ine (n=14) palyatif tedavi uygulanmıştır. Olguların aort kök ölçümleri 18.0 ile 42.5 mm arasında değişmekte olup, ortalama 27.9 ±5.3 mm’dir. Olguların %12’sinin (n=6) aort kökü dilatasyonu yok iken, %88’inin (n=44) aort kökü dilatasyonu vardır. Olguların tamamında (%100) sağ ventrikül dilatasyonu ve asendan aort dilatasyonu vardır. Transanüler yama uygulananlarda, orta ve ağır pulmoner yetmezlik daha az saptandı (p: 0.02). Sonuç: Olguların %88’inde (n: 44) aort kökü dilatasyonu saptandı. Yıllık aort kökü çapı ölçümlerinin verilmesi, Fallot tetralojili hastalarda ilerleyici aort kökü dilatasyonunun tedavisinde daha etkili bir stratejisinin planlanmasına yardımcı olacaktır.

Children’s use of value information is characterized by differential autonomic reactivity during learning

The Marfan syndrome (MFS) patients are highly predisposed to thoracic aortic aneurysm and/or dissection, with virtually every patient having evidence of aortic disease at some point during their lifetime. We conducted a meta-analysis to investigate the efficacy of angiotensin receptor blockers (ARBs) in slowing down the progression of aortic dilatation in MFS patients. PUBMED, EMBASE, and COCHRANE databases were searched for relevant articles published from inception to February 1, 2020. We included randomized clinical trials evaluating the effect of ARBs on aortic root size in patients with MFS with a follow-up period of at least 2.5 years. Seven studies were included with a total of 1,510 patients. Our analysis demonstrated a significantly smaller change in aortic root and ascending aorta dilation in the ARBs treated group when compared with placebo (mean difference 0.68; 95% confidence interval [CI] −1.31 to −0.04; p = 0.04, I2 = 94%, and mean difference −0.13, 95% CI −0.17 to −0.09; p < 0.00001, I2 = 0%, respectively). ARBs as an add-on therapy to beta-blockers resulted in a significantly smaller change in aortic root dilation when compared with the arm without ARBs (mean difference −2.06, 95% CI −2.54 to −1.58; p < 0.00001, I2 = 91%). However, there was no statistically significant difference in the number of clinical events (aortic complications/surgery) observed in the ARBs arm when compared with placebo (Risk ratio of 1.01, 95% CI 0.74 to 1.38; p = 0.94, I2 = 0%). In conclusion, ARBs therapy is associated with a slower progression of aortic root dilation when compared with placebo and as an addition to beta-blocker therapy.

Tele-Clinic Visits in Pediatric Marfan Patients using Parental Echo - Study Design, Methodology, and Parent Training

Purpose: Patients with Marfan syndrome are at risk for progressive aortic root dilation, which can lead to aortic dissection and death. These patients are monitored closely by echocardiography every 6-12 months. Since many Marfan patients live far away from specialized centers, these clinic visits represent a significant burden. We report the design, methodology, and training phase of a pilot intervention to evaluate the feasibility and reliability of tele-clinic visits using parental echocardiograms. Methods: Patients who met the following criteria are enrolled: Inclusion: 1) Marfan Syndrome by revised Ghent criteria; 2) …

Tetralogy of Fallot With Pulmonary Atresia: Anatomy, Physiology, Imaging, and Perioperative Management.

Tetralogy of Fallot (ToF) with pulmonary atresia (ToF-PA) is a complex congenital heart defect at the extreme end of the spectrum of ToF, with no antegrade flow into the pulmonary arteries. Patients differ with regard to the sources of pulmonary blood flow. In the milder spectrum of disease, there are confluent branch pulmonary arteries fed by ductus arteriosus. In more severe cases, however, the ductus arteriosus is absent, and the sole source of pulmonary blood flow is via major aortopulmonary collateral arteries (MAPCAs). The variability in the origin, size, number, and clinical course of these MAPCAs adds to the complexity of these patients. Currently, the goal of management is to establish pulmonary blood flow from the right ventricle (RV) with RV pressures that are ideally less than half of the systemic pressure to allow for closure of the ventricular septal defect. In the long term, patients with ToF-PA are at higher risk for reinterventions to address pulmonary arterial or RV-pulmonary artery conduit stenosis, progressive aortic root dilation and aortic insufficiency, and late mortality than those with less severe forms of ToF.

Comparison of Evolution of Aortic Root Dilation and Ghent Criteria in Preadolescents and Adolescents with and without Marfan Syndrome

To determine whether the Ghent Criteria (2010) can be reliably used in evaluating preadolescents and adolescents for Marfan syndrome by comparing aortic growth, systemic scores, and anthropometric features in individuals with and without Marfan syndrome. A retrospective chart review was completed for patients less than 15years of age referred for Marfan syndrome. Comparisons were made between the first and last visit. Paired t tests were used to compare Ghent systemic scores. Wilcoxon rank-sum test were used to compare age, aortic root z scores, height z scores, and body mass index z scores. Recursive partitioning was used to identify combinations of factors to distinguish Marfan syndrome. In total, 53 individuals met inclusion criteria (29 Marfan syndrome and 24 non-Marfan syndrome). Ghent systemic score increased in the Marfan syndrome group and declined in the non-Marfan syndrome. The non-Marfan syndrome group did not develop progressive aortic root dilation with age. Individuals with Marfan syndrome had higher median height z scores than non-Marfan syndrome, with no difference in median body mass index z score between groups. A combination of aortic root z score above 0.95 and Ghent systemic score above 3 was highly indicative of a Marfan syndrome diagnosis in children less than 15years of age. The Ghent criteria (2010) can be used to reliably exclude a diagnosis of Marfan syndrome in individuals less than 15years of age. Genetic testing should be used as an aide in confirming or excluding the diagnosis of Marfan syndrome in individuals with an aortic root z score above 0.95 in combination with a Ghent systemic score above 3 at initial visit.

Meta-analysis Examining the Usefulness of Angiotensin Receptor blockers for the Prevention of Aortic Root Dilation in Patients With the Marfan Syndrome

The Marfan syndrome (MFS) patients are highly predisposed to thoracic aortic aneurysm and/or dissection, with virtually every patient having evidence of aortic disease at some point during their lifetime. We conducted a meta-analysis to investigate the efficacy of angiotensin receptor blockers (ARBs) in slowing down the progression of aortic dilatation in MFS patients. PUBMED, EMBASE, and COCHRANE databases were searched for relevant articles published from inception to February 1, 2020. We included randomized clinical trials evaluating the effect of ARBs on aortic root size in patients with MFS with a follow-up period of at least 2.5 years. Seven studies were included with a total of 1,510 patients. Our analysis demonstrated a significantly smaller change in aortic root and ascending aorta dilation in the ARBs treated group when compared with placebo (mean difference 0.68; 95% confidence interval [CI] -1.31 to -0.04; p = 0.04, I2 = 94%, and mean difference -0.13, 95% CI -0.17 to -0.09; p < 0.00001, I2 = 0%, respectively). ARBs as an add-on therapy to beta-blockers resulted in a significantly smaller change in aortic root dilation when compared with the arm without ARBs (mean difference -2.06, 95% CI -2.54 to -1.58; p < 0.00001, I2 = 91%). However, there was no statistically significant difference in the number of clinical events (aortic complications/surgery) observed in the ARBs arm when compared with placebo (Risk ratio of 1.01, 95% CI 0.74 to 1.38; p = 0.94, I2 = 0%). In conclusion, ARBs therapy is associated with a slower progression of aortic root dilation when compared with placebo and as an addition to beta-blocker therapy.

Thoracic Aortic Aneurysm Surgery in Marfan Patients: a Perspective from the UK.

ObjectiveCardiovascular complications in Marfan patients include progressive aortic root dilation which can precipitate acute aortic dissection, ruptured aorta, severe aortic regurgitation, or all the aforementioned. Such complications can be fatal and the cause of death prior to any surgical intervention. We set out to identify the Marfan population in England and Wales and present their surgical outcomes.MethodsA total of 306 patients with Marfan syndrome who underwent aortic root surgery were identified between April 2007 and March 2013 from NICOR database. We examined the perioperative characteristics of such cohort along with in-hospital outcomes and survival.ResultsRoot and ascending segment procedures on Marfan patients performed in 3.3% of the total cohort by NICOR root surgery patients. The median reported age was 40 years (IQR = 29-49 years) and 100 (32.7%) were female. Of the patients analysed, 17.3% were treated non-electively and 68.6% of them received concomitant valve procedure. The in-hospital mortality was 2.0%. Reoperation for bleeding was required in 8.2% of patients and 1.3% of them suffered a cerebrovascular accident (CVA). Mortality at 1 year was reported as 5.5%.ConclusionThe outcomes of surgery on the root and ascending aorta in Marfan patients in the United Kingdom are satisfactory; however, the overall complexities of this patient population are not well understood and would benefit from further investigations.

Valve-Sparing Neoaortic Root Replacement Post Norwood

Progressive aortic root dilatation following palliation for hypoplastic left heart syndrome has become increasingly recognized and constitutes a significant issue with potential morbidity. Although little is known about the natural history and the optimal management strategy, currently the indications and optimal timing for surgical intervention are undefined and largely due to significant associated issues, most commonly important semilunar valve regurgitation and/or compromise of the Fontan circulation due to central pulmonary artery obstruction secondary to extrinsic compression by the aneurysm. A description of the technical aspect of this procedure is provided.