The effect of
mutation type on the severity of cardiovascular manifestations in patients with Marfan syndrome (MFS) has been reported with disparity results.
This study aims to determine the impact ...of the
mutation type on aortic diameters, aortic dilation rates and on cardiovascular events (ie, aortic dissection and cardiovascular mortality).
MFS patients with a pathogenic
mutation followed at two specialised units were included.
mutations were classified as being dominant negative (DN; incorporation of non-mutated and mutated fibrillin-1 in the extracellular matrix) or having haploinsufficiency (HI; only incorporation of non-mutated fibrillin-1, thus a decreased amount of fibrillin-1 protein). Aortic diameters and the aortic dilation rate at the level of the aortic root, ascending aorta, arch, descending thoracic aorta and abdominal aorta by echocardiography and clinical endpoints comprising dissection and death were compared between HI and DN patients.
Two hundred and ninety patients with MFS were included: 113 (39%) with an HI-
mutation and 177 (61%) with a DN-
. At baseline, patients with HI-
had a larger aortic root diameter than patients with DN-
(HI: 39.3±7.2 mm vs DN: 37.3±6.8 mm, p=0.022), with no differences in age or body surface area. After a mean follow-up of 4.9±2.0 years, aortic root and ascending dilation rates were increased in patients with HI-
(HI: 0.57±0.8 vs DN: 0.28±0.5 mm/year, p=0.004 and HI: 0.59±0.9 vs DN: 0.30±0.7 mm/year, p=0.032, respectively). Furthermore, patients with HI-
tended to be at increased risk for the combined endpoint of dissection and death compared with patients with DN-
(HR: 3.3, 95% CI 1.0 to 11.4, p=0.060).
Patients with an HI mutation had a more severely affected aortic phenotype, with larger aortic root diameters and a more rapid dilation rate, and tended to have an increased risk of death and dissections compared with patients with a DN mutation.
Life expectancy in Marfan syndrome patients has improved thanks to the early detection of aortic dilation and prophylactic aortic root surgery. Current international clinical guidelines support the ...use of aortic root diameter as a predictor of complications. However, other imaging markers are needed to improve risk stratification. This study aim to ascertain whether proximal aorta longitudinal and circumferential strain and distensibility assessed by cardiac magnetic resonance (CMR) predict the aortic root dilation rate and aortic events in Marfan syndrome.
One hundred and seventeen Marfan patients with no previous aortic dissection, cardiac/aortic surgery, or moderate/severe aortic regurgitation were prospectively included in a multicentre protocol of clinical and imaging follow-up. At baseline, CMR was performed and proximal aorta longitudinal strain and ascending aorta circumferential strain and distensibility were obtained. During follow-up (85.7 75.0-93.2 months), the annual growth rate of aortic root diameter was 0.62 ± 0.65 mm/year. Fifteen patients underwent elective surgical aortic root replacement and four presented aortic dissection. Once corrected for baseline clinical and demographic characteristics and aortic root diameter, proximal aorta longitudinal strain, but not circumferential strain and distensibility, was an independent predictor of the aortic root diameter growth rate (P = 0.001, P = 0.823, and P = 0.997, respectively), z-score growth rate (P = 0.013, P = 0.672, and P = 0.680, respectively), and aortic events (P = 0.023, P = 0.096, and P = 0.237, respectively).
Proximal aorta longitudinal strain is independently related to the aortic root dilation rate and aortic events in addition to aortic root diameter, clinical risk factors, and demographic characteristics in Marfan syndrome patients.
Liver cirrhosis induces cardiac alterations. We aimed to define these alterations and assess their reversibility after transplantation.
Cirrhotic patients (
n=40) and controls (
n=15) underwent ...echocardiography and stress ventriculography. Fifteen cirrhotics were reevaluated 6–12 months after transplantation.
Cirrhotics had higher left ventricular wall thickness (9.6±1.2 vs. 8.8±1.2
mm;
P<0.05) and ejection fraction (73±6 vs. 65±4%,
P<0.001) than controls. Basal diastolic function was similar. During stress, cirrhotics presented lower increases of heart rate, left ventricular ejection fraction, stroke volume and cardiac index (
P<0.05 for all), and diastolic dysfunction with lower ventricular peak filling rate (
P=0.001). Exercise capacity was reduced (48±21 vs. 76±24
W;
P<0.001). Ascitic patients exhibited more diastolic dysfunction at rest and during stress compared to non-ascitic patients. Liver transplantation caused regression of ventricular wall thickness (10.2±1.3 vs. 9.5±1.2
mm;
P<0.05), improvement of diastolic function, and normalization of systolic response and exercise capacity during stress (significant increases in heart rate, ventricular ejection fraction, stroke volume and cardiac index;
P<0.05 for all).
Cardiac alterations in cirrhosis present with mild increases in ventricular wall thickness, diastolic dysfunction that worsens with ascites and physical stress, and abnormal systolic response to stress limiting exercise capacity. Liver transplantation reverses these alterations.
Abstract Background Previous studies demonstrated the usefulness of MRI in the evaluation of aortic biomechanics in Marfan patients with aortic dilatation. However, these parameters have not been ...well studied in earlier stages of aortic disease. The present work aimed to study aortic biomechanics: aortic distensibility (AD) and pulse wave velocity (PWV), by MRI in Marfan patients without advanced aortic disease. Methods Eighty consecutive Marfan patients were compared with 36 age- and sex-matched controls. MRI images at the level of ascending, descending and abdominal aorta were used to determine AD and PWV. Results Marfan patients (27 men; age: 32.0 ± 10.5 years; mean aortic root diameter: 37.2 ± 4.6 mm) had lower AD at all levels (ascending 2.6 ± 2.1 vs. 6.2 ± 3.7 mm Hg − 1 · 10 − 3 , p < 0.001; descending 3.1 ± 2.0 vs. 8.3 ± 4.2, p < 0.001; and abdominal 4.5 ± 2.2 vs. 14.0 ± 5.2, p < 0.001), higher aortic arch PWV (8.1 ± 6.5 vs. 4.3 ± 1.8 m/s, p < 0.01) and ascending-to-abdominal PWV (6.1 ± 3.0 vs. 4.7 ± 1.5 m/s, p < 0.01) compared with controls. Thirty-five Marfan patients had a non-dilated aortic root (mean aortic root diameter: 34.5 ± 3.8 mm). In multivariable analyses, after adjustment for age, pulse pressure and aortic dimensions, AD remained lower and PWV higher in Marfan patients; even Marfan patients with non-dilated aortic root showed impaired aortic biomechanics compared with controls. Z -score for ascending AD < − 3.5 distinguished Marfan patients from controls with 82.5% sensitivity and 86.1% specificity. Conclusions Aortic biomechanics by MRI were abnormal in the entire aorta in Marfan patients. Moreover, Marfan patients without dilated aortic root showed clear impairment of aortic biomechanics, which suggests that they may be used as early markers of aortic involvement in these patients.
Bicuspid aortic valve (BAV) disease is associated with faster aortic valve degeneration and a high incidence of aortic stenosis (AS). In this study, we aimed to identify differences in the ...pathophysiology of AS between BAV and tricuspid aortic valve (TAV) patients in a multiomics study integrating metabolomics and transcriptomics as well as clinical data.
Eighteen patients underwent aortic valve replacement due to severe aortic stenosis: 8 of them had a TAV, while 10 of them had a BAV. RNA sequencing (RNA-seq) and proton nuclear magnetic resonance spectroscopy (1H-NMR) were performed on these tissue samples to obtain the RNA profile and lipid and low-molecular-weight metabolites. These results combined with clinical data were posteriorly compared, and a multiomic profile specific to AS in BAV disease was obtained.
H-NMR results showed that BAV patients with AS had different metabolic profiles than TAV patients. RNA-seq also showed differential RNA expression between the groups. Functional analysis helped connect this RNA pattern to mitochondrial dysfunction. Integration of RNA-seq, 1H-NMR and clinical data helped create a multiomic profile that suggested that mitochondrial dysfunction and oxidative stress are key players in the pathophysiology of AS in BAV disease.
The pathophysiology of AS in BAV disease differs from patients with a TAV and has a specific RNA and metabolic profile. This profile was associated with mitochondrial dysfunction and increased oxidative stress.
Aims To investigate the clinical features, echocardiographic characteristics, management, and prognostic factors of mortality of aorto-cavitary fistulization (ACF) in infective endocarditis (IE). ...Extension of infection in aortic valve IE beyond valvular structures may result in peri-annular complications with resulting necrosis and rupture, and subsequent development of ACF. Aorto-cavitary communications create intra-cardiac shunts, which may result in further clinical deterioration and haemodynamic instability. Methods and results In a retrospective multi-centre study over 4681 episodes of IE, a total of 76 patients with ACF 1.6%, confidence interval (CI) 95%: 1.2–2.0% diagnosed by echocardiography or during surgery were identified. Fistulae were found in 1.8% of cases of native valve IE and in 3.5% of cases of prosthetic valve IE from the general population and in 0.4% of drug abusers. PVE was present in 31 (41%) cases of ACF. Transthoracic and transoesophageal echocardiography detected the fistulous tracts in 53 and 97% of cases, respectively. Peri-annular abscesses were detected in 78% of cases, fistulae originated in similar rates from the three sinuses of Valsalva, and the four cardiac chambers were equally involved in the fistulous tracts. Heart failure (HF) developed in 62% of cases and surgery was performed in 66 (87% CI 95% 77–93%) patients with a mortality of 41% (95% CI 30–53%) in the overall population. Multivariate analysis identified HF (OR 3.4, CI 95% 1.0–11.5), prosthetic IE (OR 4.6, CI 95% 1.4–15.4) and urgent or emergency surgical treatment (OR 4.3, CI 95% 1.3–16.6) as variables significantly associated with an increased risk of death. Major complications during follow-up (death, re-operation, or re-admission for HF) among the five operative survivors with residual fistulae occurred in 20 and 100% of patients at 1 and 2 years, respectively. Conclusion Aorto-cavitary fistulous tract formation is an uncommon but extremely serious complication of IE. In-hospital mortality was exceptionally high despite aggressive management with surgical intervention in the majority of patients. Prosthetic IE, urgent surgery, and the development of HF identify the subgroup of patients with IE and ACF that have significantly increased risk of in-hospital death.
Abstract Bicuspid aortic valve (BAV) is the most common adult congenital heart defect and is found in 0.5% to 2.0% of the general population. The term “BAV” refers to a heterogeneous group of ...disorders characterized by diverse aortic valve malformations with associated aortopathy, congenital heart defects, and genetic syndromes. Even after decades of investigation, the genetic determinants of BAV and its complications remain largely undefined. Just as BAV phenotypes are highly variable, the genetic etiologies of BAV are equally diverse and vary from complex inheritance in families to sporadic cases without any evidence of inheritance. In this paper, the authors discuss current concepts in BAV genetics and propose a roadmap for unraveling unanswered questions about BAV through the integrated analysis of genetic and clinical data.
Non-syndromic aortic disease (NSAD) is a frequently asymptomatic but potentially lethal disease characterised by familial cases of thoracic aortic aneurysms and dissections. This monogenic but ...genetically heterogeneous condition is primarily inherited as an autosomal dominant disorder with low penetrance and variable expression. Mutations in ACTA2, TGFBR1, TGFBR2, MYH11, SMAD3, MYLK, and FBN1 genes have been described but still, there are many unresolved familial cases.
The whole exome of two distantly related and affected members of a Spanish family with multiple cases of NSAD was analysed through 5500 SOLiD™ System for the identification of shared and putative pathogenic variants.
A new mutation termed c.C1042T:p.R348C (NM_001135599.2) was identified in TGFB2, a gene located in an evolutionary highly conserved region (Chr1: 218,519,577-218,617,961) that has been recently connected to this disease. The analysis of other family members using capillary sequencing confirmed cosegregation of the mutation with the disease and its incomplete penetrance.
The repeated implication of TGFB2 in the development of thoracic aortic aneurysms and dissections suggests that this gene should be considered during genetic diagnosis of this disease. An accurate diagnosis of affected individuals and additional family members at risk allows for a personalised and more efficient gene-based follow-up and treatment. Finally, the reiterative presence of common musculoskeletal and craniofacial additional features in patients with TGFB2 mutations suggests the existence of a new yet undefined connective tissue syndrome responsible for not only aortic dilation, but also for the other extracardiac alterations present in the affected patients.
•Genetic diagnosis of a non-syndromic aortic disease familial case was conducted.•The whole exome of two distant and affected relatives was sequenced.•One shared and putative pathogenic variant was identified in TGFB2.•TGFB2 should be regarded during genetic diagnosis of patients with aortic disease.•Non-syndromic diagnosis of these patients should be reconsidered.
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