Background Familial thoracic aortic aneurysm and dissection is a genetic condition frequently presenting without syndromic features or early symptoms, and it often warrants restrictive sports advice. Case Summary A masters dressage rider presented with palpitations and atypical thoracic discomfort. Cardiac magnetic imaging revealed an aortic root of 47 mm. Genetic testing confirmed a pathogenic class V LTBP3 variant consistent with familial thoracic aortic aneurysm and dissection. Although prophylactic surgery was considered given subsequent growth to 49 mm, continued surveillance was chosen after shared decision-making, as the aortic root diameter did not reach the surgical threshold and remained stable during 5 years of follow-up. The patient competed in multiple international competitions, without evidence of accelerated root growth. Discussion Dressage is unlikely to contribute to aortic root progression in genetically predisposed athletes. Take-Home Message In athletes, decisions about timing of intervention should consider sport-specific hemodynamic demands and force distribution, aortic dimensions and growth, symptom burden, and athlete ambitions and goals.

BACKGROUND:Aortic root surgery in patients with Marfan syndrome (MFS) has significantly improved survival, allowing time for distal aortic complications such as type B aortic dissection (TBAD) to emerge. The implantation of a non-compliant synthetic graft may alter aortic biomechanics and hemodynamics, potentially contributing to these late complications. This proof-of-concept study aimed to assess changes in aortic motion and flow characteristics following aortic root surgery using advanced cardiovascular magnetic resonance (CMR) techniques. METHODS:Three MFS patients (aged 26-37 years), two males, one female, undergoing valve-sparing aortic root surgery, were prospectively studied before and 6 months after surgery. All participants underwent non-contrast-enhanced four-dimensional (4D) balanced steady-state free precession and 4D flow CMR at 3T. A deep learning-based segmentation pipeline (nnU-Net) provided segmentations utilized for calculation of aortic displacement, distensibility, regional wall shear stress (WSS) and velocity, and global pulse wave velocity (PWV). RESULTS:Postoperatively, all patients exhibited markedly decreased ascending aorta (AAo) volume. Three-dimensional distensibility (10⁻³ mmHg⁻¹) also decreased: patient 1, from 4.1 to 1.7; patient 2, from 3.4 to 1.2; and patient 3, from 2.9 to 1.5. Displacement in the AAo, especially at the sinotubular junction, was substantially reduced, consistent with the rigidity of the implanted graft. In the descending aorta (DAo), distensibility and displacement showed increases in two patients and a decrease in one. Peak systolic velocity and WSS increased in the AAo for all patients, whereas DAo values remained largely unchanged. PWV change varied between patients: decreasing slightly in patient 1, from 8.4 to 7.9 m/s, but increased in patients 2 and 3 (8.0 to 8.9 m/s and 6.2 to 9.8 m/s, respectively. CONCLUSION:This study demonstrated that AAo biomechanics and hemodynamics change predictably following valve-sparing aortic root surgery in MFS, while changes in the DAo were not consistent between patients. Further research with larger sample sizes is required to identify which of these changes are linked to specific disease profiles and whether parameter combinations can indicate a predisposition to TBAD.

AIMS:Patients suffering from Marfan syndrome (MFS), the most prevalent inherited connective tissue disorder, face premature mortality due to dissection and rupture of thoracic aortic aneurysms. Here, we questioned whether myeloperoxidase (MPO), a leucocyte-derived enzyme with high affinity to the vessel wall, contributes to aortic remodelling in MFS. METHODS AND RESULTS:Plasma MPO levels were evaluated in MFS patients and healthy controls. Thoracic aortic aneurysm formation was determined in heterozygous transgenic Fbn1C1041G/+ (MFS) mice, MPO-deficient MFS mice (MFSxMpo-/-), and MFS mice treated with an MPO inhibitor by ultrasound and histology.MFS patients exhibited increased circulating MPO levels and marked aortic MPO deposition. In MFS mice, MPO-deficiency reduced aortic elastin fragmentation and aneurysm formation. RNA sequencing revealed an inflammatory gene program in aortic endothelial cells isolated from MFS mice in comparison to WT and MFSxMpo-/- mice. This was accompanied by enhanced endothelial expression of the leucocyte adhesion molecule ICAM-1, increased leucocyte adhesion, and, consequently, leucocyte infiltration in MFS aortae. Moreover, MPO directly contributed to adverse extracellular matrix remodelling through overproduction of reactive oxygen species and subsequent vascular protein modifications leading to enhanced matrix metalloproteinase 2/9 activity. Lastly, treatment of MFS mice with the orally available MPO inhibitor AZM198 attenuated TAA formation. CONCLUSION:MPO is increased in MFS and contributes to thoracic aortic dilatation by inducing inflammatory endothelial activation, oxidative stress, and adverse extracellular matrix remodelling. Pharmacological and genetic inhibition of MPO reduced MFS-related aortic dilation in mice, highlighting MPO as a promising therapeutic target in MFS.

BACKGROUND:Marfan syndrome (MFS) patients with a history of aortic root surgery (ARS) are at increased risk of type B aortic dissection, possibly because the noncompliant graft fails to absorb systolic forces, leading to undampened flow in the proximal descending aorta (pDAo). In this study, we investigated the magnitude and location of abnormal aortic displacement and wall shear stress (WSS) using cardiac magnetic resonance (CMR) imaging. METHODS:We examined 82 MFS patients (32 with ARS, 34 ± 8 years, 36 women) and 45 age- and sex-matched controls, all undergoing four-dimensional high-resolution balanced steady-state free precession and flow CMR. Peak displacement and WSS were calculated using automated aortic segmentations. Heatmaps were created to identify and quantify regions with abnormal displacement and WSS. The surface areas of abnormal displacement and WSS were quantified in four aortic regions. The Wilcoxon signed-rank test was used for comparison of abnormal CMR parameter quantification, and Pearson correlation was used to assess correlations between displacement and WSS. RESULTS:WSS was higher in the proximal (p < 0.001) and distal ascending aorta (Aao) (p = 0.031) of ARS MFS patients compared to native MFS patients. ARS MFS patients had significantly larger surface areas of decreased displacement (p < 0.001; present in 97% (31/32) of ARS MFS patients) and increased WSS (p < 0.001; present in 100% (32/32) of patients) in the proximal Aao. There was a trend toward a larger surface area of increased displacement in the pDAo of ARS MFS patients (p = 0.062; present in 72% (23/32) of patients), mainly located in the outer pDAo. pDAo displacement was positively correlated with pDAo WSS (Pearson r = 0.46 [95% confidence interval: 0.13, 0.70], p = 0.008). CONCLUSION:Aortic displacement and flow characteristics are abnormal in MFS patients, both with and without a history of ARS. ARS MFS patients exhibit distinct features in both the AAo and descending aorta (DAo), particularly in the proximal DAo, which is the region susceptible to type B aortic dissections.

Marfan syndrome is a heritable connective tissue disorder associated with cardiovascular complications, including progressive aortic aneurysm and dissection, caused by mutations in the fibrillin-1 (FBN1) gene. We generated human induced pluripotent stem cells (hiPSCs) from skin fibroblasts of 3 patients carrying FBN1 mutations (FBN1 c.6554 T > C, FBN1 c.4425-4426delinsC, FBN1 c.6806 T > C) using an episomal vector reprogramming system. These hiPSC lines exhibit pluripotent stem cell morphology, express established markers of undifferentiated hPSC state, maintain a normal karyotype, and differentiation potential into the 3 germ layers. These hiPSC lines provide a cellular model to investigate Marfan syndrome and its associated cardiovascular pathology in vitro.

AIMS:Limited data indicates that athletes' hearts demonstrate decreased native T1, but this assertion has not been replicated in large cohorts of extreme phenotypes of elite athletes. Therefore, we investigated differences in native T1 between elite athletes and healthy non-athletic controls. METHODS AND RESULTS:Cross-sectional analysis comparing native T1 between elite athletes (≥16 years; ≥10 h of exercise/week) and age-matched healthy non-athletic controls. All participants underwent cardiovascular magnetic resonance imaging on a 1.5 tesla MRI machine. We included 240 elite athletes [50% women; age 28 years (25-32)] and 80 non-athlete healthy controls [50% women; age 28 years (23-39)]. Elite athletes demonstrated lower native T1 than non-athlete healthy controls (960 ± 21 ms vs. 983 ± 26 ms, P < 0.001), also when stratified by sex (male athletes vs. controls 953 ms ±19 vs. 968 ms ±16, P < 0.001; female athletes vs. controls 968 ms ±20 vs. 999 ms ±25, P < 0.001). Multivariate linear regression identified elite athlete status (β = -13.34, P < 0.001), heart rate (β = 0.6, P < 0.001), average left-ventricular wall thickness (β = -8.28, P < 0.001) and native blood pool T1 (β = 0.09, P < 0.001) as independent determinants of native T1 (adjusted R2 = 51.4%, P < 0.001). CONCLUSION:Elite athletes have lower native T1 compared with non-athletes, both in women and men. Athlete- and sex-specific reference ranges should be applied when interpreting native T1 in athlete populations, especially in female athletes.

INTRODUCTION:Patients with connective tissue disease and aortic root aneurysm are at risk of dissection and progression of the dilatation. Standard treatment of aortic root aneurysm is either a total root replacement or valve-sparing root replacement. Both procedures have drawbacks, such as the need for anticoagulation and long-term exposure to the chance of reoperation or endocarditis. The ExoVasc personalized external aortic root support (PEARS) is a perivascular stent that has been introduced to reduce these risks while aiming for a similar beneficial outcome on late aortic complications. We sought to report the safety and efficacy of PEARS in the first 90 patients with connective tissue disease and aortic root aneurysm in the Netherlands. METHODS:From January 2018 to February 2023, in 2 affiliated centers 90 patients underwent surgery with the intention of either an isolated PEARS procedure, or PEARS as a concomitant procedure or a Ross-PEARS procedure. Isolated PEARS was generally performed off-pump under sustained induced hypotension. Patient characteristics, preoperative and postoperative echocardiography, and computed tomography or magnetic resonance imaging findings were assessed. RESULTS:Median age was 37 (±15 standard deviation) years, and 62 (69%) patients were male. Among all patients, 37% had Marfan syndrome, 8% Loeys-Dietz syndrome, and 32% had a bicuspid aortic valve. Sixty (67%) patients were planned for isolated PEARS, 21 (23%) underwent Ross-PEARS, and 9 (10%) patients underwent PEARS as a concomitant procedure. Mean aortic root diameter at the level of the sinus of Valsalva was 44.6 ± 7.0 mm before surgery and 38.6 ± 5.6 mm at the follow-up (P < .001). Two patients in the isolated PEARS group were converted to conventional surgery, resulting in a procedural success rate of 96.6%. One Ross PEARS patient had to be reoperated on the first postoperative day because of compression of the RCA by the PEARS prosthesis. Median follow-up duration was 6 months (interquartile range, 3-18; range, 0-45). No death, endocarditis, or dissection occurred during follow-up. One patient had a transient ischemic attack 1 year after surgery (mitral valve plasty and PEARS as concomitant procedure). Three patients were reoperated in the follow-up period. At follow-up aortic root and ascending aortic diameters were all significantly reduced. CONCLUSIONS:The PEARS procedure can be performed with acceptable operative risk and no dissections were observed during follow-up. PEARS has been adapted as a valid alternative treatment strategy in our centers. Complications related to coronary artery origin are an important issue.

BACKGROUND:Myocardial late gadolinium enhancement (LGE) using cardiac magnetic resonance imaging has been described in older endurance athletes, particularly at the ventricular hinge point. However, data on young, elite athletes are lacking. We therefore quantified the prevalence of hinge point LGE (HP-LGE) in young elite-level athletes. METHODS:We investigated 309 (40% women; median age 25.1 [21.9-29.5] years) asymptomatic athletes included in the ELITE prospective cohort (Evaluation of Lifetime Participation in Intensive Top-level Sports and Exercise cohort), investigating cardiovascular screenings of elite (national-, international-, Olympic-, or Paralympic-) level athletes, including cardiac magnetic resonance imaging with short-axis cine imaging, LGE, and T1-mapping. RESULTS:A total of 124 (40%) athletes had HP-LGE, with a higher prevalence in men compared with women (47% versus 30%; P=0.004). When indexed for body surface area, athletes with HP-LGE had greater left ventricle end-systolic volumes (53±11 mL/m² versus 51±11 mL/m²; P=0.037), right ventricle end-systolic volumes (56±12 mL/m² versus 53±11 mL/m²; P=0.020), lower left ventricle ejection fraction (55.5±5.0% versus 56.7±4.6%; P=0.035), lower right ventricle ejection fraction (53.9±5.0% versus 55.2±4.4%; P=0.021), and smaller estimated global left ventricle extracellular volumes (24.45±2.52% versus 25.27±2.59%; P=0.015). In multivariable regression analyses, male sex was strongly associated with HP-LGE (odds ratio, 3.07 [95% CI, 1.32-7.32]; P=0.010). CONCLUSIONS:HP-LGE is a common finding in asymptomatic, elite athletes and is strongly associated with sex. Lower left ventricle ejection fraction is moderately associated with HP-LGE. Our study's HP-LGE prevalence indicates that HP-LGE should be interpreted as a feature of the athlete's heart.

BACKGROUND:Acute aortic syndromes in Marfan syndrome (MFS) often occur before reaching the surgical diameter threshold, highlighting the need for new imaging biomarkers. OBJECTIVES:Aim was to compare cardiovascular magnetic resonance (CMR)-derived aortic three-dimensional (3D) distensibility and displacement in MFS patients with or without a history of aortic root surgery (RR or native) and healthy volunteers. METHODS:The participants underwent 3T CMR of the thoracic aorta using an accelerated non-contrast-enhanced, free breathing, 3D cine balanced steady state free precession sequence, with spatiotemporal resolution: (1.0 mm)3/∼33ms. A deep learning-based algorithm was used to obtain aorta segmentations. Non-rigid registration of these segmentations was subsequently used to calculate 3D distensibility and its separate components: 2-dimensional distensibility, longitudinal strain, and displacement in the ascending (AAo) and descending aorta (DAo). RESULTS:Forty-seven volunteers, 51 native, and 33 RR MFS patients were included. AAo and DAo distensibility (10-3*mmHg-1) were different for healthy volunteers vs native vs RR patients (AAo: 5.1±1.4 vs 3.6±1.4 vs. 1.4±0.7, p<0.001, DAo: 3.2±1.1 vs. 2.5±0.9 vs 2.4±1.0, p=0.001). Sinotubular junction displacement (mm) was significantly higher for healthy volunteers vs native MFS vs RR MFS patients (10.3±1.3 vs 8.7±2.1 vs 5.7±1.6, p<0.001). In native patients, age (β=-0.06 (95% CI:-0.10 to -0.01), p=0.014) and root diameter (β=-0.1 (95% CI: -0.19 to -0.02), p=0.018) were negatively associated with AAo 3D distensibility, independent of male sex, body surface area, and aortic tortuosity index. CONCLUSION:Aortic 3D distensibility and displacement, derived from 4-dimensional CMR, were significantly diminished in MFS compared to volunteers and should be investigated longitudinally to assess their potential value in predicting aortic events and guiding therapy.

AIMS:Differentiating physiological exercise-induced cardiac remodelling (EICR) from pathology is challenging, especially in female athletes, where studies using state-of-the-art imaging techniques are lacking. We aimed to investigate extreme phenotypes of EICR in female elite athletes using magnetic resonance imaging (MRI). METHODS AND RESULTS:Cross-sectional, multicentre study in female elite athletes using contrast-enhanced cardiac MRI. Left and right ventricle (LV, RV) indices and LV mass (LVM)-to-LV end-diastolic volume (EDV) ratios were investigated, indexed by body surface area (BSA). Cardiac remodelling was determined comparing cardiac MRI metrics to female reference values, stratified by ESC sports classification (endurance, mixed, power/skill). In 173 female elite athletes (median age 25 years, median 18 h training/week, 97% Caucasian), mean LV EDV/BSA and LVM/BSA were 108 ± 13 mL/m2 and 50 ± 10 g/m2, with lower LVM/LV EDV ratios (0.5 ± 0.1) than the general population (0.7 ± 0.1 g/mL; P < 0.001). Most athletes (71%) had isolated LV EDV increases; LVM increases (18%) commonly coincided with LV EDV increases. Compared with the general population (45 ± 7 g/m2), only mixed (48 ± 9 g/m2; P = 0.021) and endurance athletes (53 ± 11 g/m2; P < 0.001) exhibited greater mean LVM with endurance athletes surpassing mixed athletes (P = 0.004). Mixed and endurance showed comparably greater median biventricular EDV compared with power/skill athletes [LV: 109 (103-119) and 111 (101-118) vs. 99 (92-105); RV: 110 (103-118) and 112 (105-124) vs. 101 (95-104) mL/m2; P < 0.001]. Maximum wall thickness > 11 mm was rare (2%). Global T1 time was 968 ± 22 ms; extracellular volume was 25 ± 4%. CONCLUSION:Female elite athletes, particularly endurance-trained athletes, display EICR marked by increased ventricular volumes, without prominent increases in LVM or wall thickness. TRIAL REGISTRATION NUMBER:NL9328.

BACKGROUND:New treatment strategies are required to reduce aortic events in Marfan syndrome (MFS). Resveratrol is a dietary supplement that intervenes in aortic wall cellular metabolism and may benefit MFS patients. PURPOSE:To evaluate whether treatment with Resveratrol affects aorta hemodynamics derived from 4D flow MRI in MFS. STUDY TYPE:Prospective single-arm open-label multicenter trial. POPULATION:46 MFS patients (mean age 36 ± 9 years, 23 female), 20 with and 26 without a history of aortic root surgery (RR and native MFS), and 25 age- and sex-matched healthy controls. FIELD STRENGTH/SEQUENCE:3T, temporally resolved 3D phase contrast (4D flow MRI) and 3D mDixon sequences. ASSESSMENT:MFS patients underwent 4D flow MRI before (baseline) and after 1 year of 500 mg daily Resveratrol treatment (follow-up). Velocity magnitude and wall shear stress (WSS) in six regions in the thoracic aorta were evaluated. Incidence maps showing abnormal hemodynamics compared to healthy controls were generated. Pulse wave velocity (PWV) was assessed in 45 subjects. The relationships between MRI parameters and annual aortic growth from the 3D mDixon scans and age were investigated. STATISTICAL TESTS:Student's paired and unpaired t-tests, Fisher's exact tests, McNemar's exact test, and Pearson correlation coefficients (r). Statistical significance was defined as p < 0.05. RESULTS:No significant changes in any of the hemodynamic parameters were observed: inner descending aorta WSS (Pa), native: from 1.08 ± 0.21 to 1.08 ± 0.17, p = 0.818, RR: from 1.02 ± 0.29 to 0.98 ± 0.21, p = 0.270; velocity (m/s), native: from 0.64 ± 0.10 to 0.65 ± 0.10, p = 0.359, RR: 0.68 ± 0.15, to 0.67 ± 0.12, p = 0.629; abnormally directed WSS incidence: native: from 17 (65%) to 14 (54%), p = 0.453, RR: 13 (65%) to 13 (65%), p = 1.000; PWV (m/s) native: from 7.7 ± 1.9 to 7.9 ± 1.8, p = 0.582, RR: 9.2 ± 1.6 to 8.2 ± 3.2, p = 0.184. PWV correlated with age in RR MFS patients (r = 0.59, n = 19). DATA CONCLUSION:No significant changes in aortic hemodynamics derived from 4D flow MRI were observed after 1 year of Resveratrol treatment. EVIDENCE LEVEL:1. TECHNICAL EFFICACY:Stage 4.

Abstract Background Marfan syndrome (MFS) is a genetic connective tissue disease with an increased risk for aortic root dilatation and aortic dissection. Current guidelines, based on expert consensus, recommend exercise restrictions due to concerns that exercise-induced hemodynamic stress may accelerate aortopathy. Studies examining exercise characteristics and their association with aortopathy in MFS patients are lacking. Purpose To assess the association of lifelong exercise characteristics (volume, intensity and type) with the presence of aortic dilatation in MFS patients. Methods An international multi-centre study was conducted in MFS adults. Patients were classified as sedentary (<500 metabolic equivalent of task minutes per week [MET-min/wk]), active (500-1000 MET-min/wk), or highly active (≥1000 MET-min/wk) based on lifelong exercise volumes assessed by a validated questionnaire. Patient’s dominant exercise intensity was classified as moderate (3-6 MET) or vigorous (≥6 MET), and sport type as skill, power, mixed, or endurance. Echocardiography was used to assess diameters at the sinuses of Valsalva (SoV) and ascending aorta (AA), and Campens Z-scores were calculated. Aortic dilatation was evaluated as a diameter ≥40, ≥45 mm, a Z-score ≥2 or ≥3 respectively. Results 315 patients (36[27-49] years, 53% male) were included of which 104 were sedentary, 77 active and 134 highly active (Fig. 1). 42 patients did not perform sport-related exercise, whereas 147 and 121 patients predominantly participated in moderate or vigorous intensity sports. Patients performing sports were allocated to the skill (n=13), power (n=27), mixed (n=158), endurance (n=66) or non-dominant (n=9) exercise type group. Mean SoV and AA diameters were 42.9±7.7 mm and 33.9±7.3 mm. SoV or AA diameters of ≥40 mm were present in 200 (64%) and 41 (13%) patients, whereas 223 (71%) and 81 (26%) patients had a Z-score ≥2 for the SoV or AA. Exercise volume was not associated with SoV dilatation (Fig. 2). Moderate and vigorous intensity sports were associated with a lower prevalence of SoV Z-score ≥3. Power sport was associated with a lower prevalence of all definitions of SoV dilatation, whereas mixed and endurance sports were associated with a lower prevalence of SoV Z-score ≥3. No associations were found with AA dilatation. Of the 17 (5%) patients who suffered from an aortic dissection, 1 case occurred during walking (type A dissection) whereas all other cases were not exercise-related. Conclusions Lifelong exercise volumes were not associated with aortic dilatation in MFS patients. Power sports and vigorous intensity exercise were inversely related to SoV dilatation. Further investigation is warranted to clarify whether this association reflects that patients engaging in these activities have a less severe cardiovascular phenotype, or that they are protected from exercise-related aortic complications, and if patients may miss health benefits due to too exercise restrictions.

A 62-year-old recreational cyclist presented with transient loss of consciousness and common electrocardiographic findings. Despite absence of left ventricular hypertrophy, multidisciplinary evaluation and a positive family history led to the diagnosis of non-classical Fabry disease. This case emphasizes the added value of multidisciplinary analysis of nonspecific findings to diagnose a rare disease.

OBJECTIVE:Longitudinal consequences and potential interactions of COVID-19 and elite-level sports and exercise are unclear. Therefore, we determined the long-term detrimental cardiac effects of the interaction between SARS-CoV-2 infection and the highest level of sports and exercise. METHODS:This prospective controlled study included elite athletes from the Evaluation of Lifetime participation in Intensive Top-level sports and Exercise cohort. Athletes infected with SARS-CoV-2were offered structured, additional cardiovascular screenings, including cardiovascular MRI (CMR). We compared ventricular volumes and function, late gadolinium enhancement (LGE) and T1 relaxation times, between infected and non-infected elite athletes, and collected follow-up data on cardiac adverse events, ventricular arrhythmia burden and the cessation of sports careers. RESULTS:We included 259 elite athletes (mean age 26±5 years; 40% women), of whom 123 were infected (9% cardiovascular symptoms) and 136 were controls. We found no differences in function and volumetric CMR parameters. Four infected athletes (3%) demonstrated LGE (one reversible), compared with none of the controls. During the 26.7 (±5.8) months follow-up, all four athletes resumed elite-level sports, without an increase in ventricular arrhythmias or adverse cardiac remodelling. None of the infected athletes reported new cardiac symptoms or events. The majority (n=118; 96%) still participated in elite-level sports; no sports careers were terminated due to SARS-CoV-2. CONCLUSIONS:This prospective study demonstrates the safety of resuming elite-level sports after SARS-CoV-2 infection. The medium-term risks associated with SARS-CoV-2 infection and elite-level sports appear low, as the resumption of elite sports did not lead to detrimental cardiac effects or increases in clinical events, even in the four elite athletes with SARS-CoV-2 associated myocardial involvement.

Background: Systemic right ventricular (sRV) physiology occurs in patients with congenitally corrected transposition of the great arteries (ccTGA) and D-TGA post atrial switch repair, and the natural history is of progressive sRV dysfunction. No study has assessed longitudinal changes in sRV remodeling by serial cardiovascular magnetic resonance (CMR). Methods: Patients evaluated at two adult congenital heart disease centers and who underwent >= 2 CMR exams were studied. Indexed sRV end-diastolic volume (sRVEDVi), end-systolic volume (sRVESVi), and ejection fraction (sRVEF) were determined by a core laboratory. Concurrent echocardiograms were assessed for degree of systemic tricuspid regurgitation (sTR). Tricuspid valve events were defined as >= moderate sTR, or interval tricuspid valve replacement (TVR). Generally, the earliest and most recent studies were compared. A subset of patients were followed with >= moderate sTR, and then subsequently underwent interval TVR. For these patients, two study time intervals were defined to analyze the impact of each event independently. Results: Sixty-seven patients were studied (33 +/- 11 years, 48% [32/67] male, 33% [22/67] ccTGA), with 72 total time intervals studied (median interval 9.0 years [interquartile range 4.6-13.3]). There was a small increase in sRVEDVi over time (AsRVEDVi 5.5 +/- 15.8 mL/m2, p < 0.001), but mean change in sRVEF was not significant (AsRVEF 0.1 +/- 6.9%, p = 0.86); notably, confidence intervals (CI) were wide for both. ccTGA patients had a trend toward greater decrement in sRVEF (AsRVEF -1.7 +/- 6.8 vs 1.3 +/- 6.7%, p = 0.06). For each 25 mL/m2 increase in baseline sRVEDVi, there was a 1.8% decrease in sRVEF (95% CI -3.2% to -0.5%, p = 0.01). Patients without significant sTR had lesser deterioration in sRVEF compared to those with >= moderate sTR or with interval TR intervention (AsRVEF 1.8 +/- 6.9% vs -2.1 +/- 6.6% and -2.6 +/- 4.5, p < 0.05). Interval sRV conduction delay was associated with a trend toward greater decrements in sRVEF (AsRVEF -3.9 +/- 6.3 vs 0.9 +/- 6.8%, p = 0.07). Overall, underlying congenital anatomy, baseline sRVEDVi, advanced sTR or interval TVR, and sRV conduction delay explained only 16% of the variability in AsRVEF over time. Conclusion: Longitudinal changes in sRV remodeling were small, with great heterogeneity. Apparent risk factors in our study, namely underlying congenital anatomy, baseline sRVEDVi, TR events, and sRV conduction disease accounted for only 16% of the variability seen in the longitudinal change of sRVEF.

BACKGROUND:Resveratrol, a dietary supplement that intervenes in cellular metabolism, has been shown to reduce aortic growth rate in a mouse model of Marfan syndrome (MFS), a condition associated in humans with life-threatening aortic complications, often preceded by aortic dilatation. The primary objective of this study was to investigate the effects of resveratrol on aortic growth rate in patients with MFS . METHODS:In this investigator-initiated, single-arm open-label multicentre trial, we analysed resveratrol treatment in adults aged 18-50 years with MFS. The primary endpoint was the change in estimated annual aortic growth at five predefined levels in the thoracic aorta after 1 year of resveratrol treatment, evaluated using a linear mixed model. Aortic diameters were measured by cardiac MRI at three time points to analyse the annual aortic expansion rate before and after initiation of treatment. Additionally, annual aortic growth was compared with growth in a previously conducted losartan randomised clinical trial. RESULTS:898 patients were screened of which 19% (168/898) patients met the inclusion criteria.36% (61/168) patients signed informed consent and 93% (57/61) aged 37±9 years, of which 28 males (49%) were included in the final analysis of the study. 46% (26/57) had undergone aortic root replacement prior to the study. Aortic root diameters remained stable after 1.2±0.3 years of resveratrol administration. A trend towards a decrease in estimated growth rate (mm/year) was observed in the aortic root (from 0.39±0.06 to -0.13±0.23, p=0.072), ascending aorta (from 0.40±0.05 to -0.01±0.18, p=0.072) and distal descending aorta (from 0.32±0.04 to 0.01±0.14, p=0.072). CONCLUSION:Resveratrol treatment for 1 year may stabilise the aortic growth rate in adult patients with MFS. However, a subsequent randomised clinical trial with a longer follow-up duration and a larger study cohort is needed to establish an actual long-term beneficial effect of this dietary supplement in patients with MFS. TRIAL REGISTRATION NUMBER:NL66127.018.18.