Vertebral artery dissection caused by atlantoaxial dislocation in a patient with Marfan syndrome.

A small number of case reports have documented a link between atlantoaxial dislocation (AAD) and vertebral artery dissection (VAD), but this association has never been described in patients with hereditary connective tissue disorders. We present a case of an 18-year-old female patient, diagnosed with Marfan syndrome since the age of one, who underwent brain MRA for intracranial aneurysm screening revealing tortuosity of the internal carotid and vertebral arteries as well as atlantoaxial dislocation. Since the patient was asymptomatic, a wait-and-see approach was chosen, but a follow-up MRA after 18 months showed the appearance of a dissecting pseudoaneurysm of the V3 segment of the left vertebral artery. Despite the patient being still asymptomatic, it was decided to proceed with C1-C2 stabilization to prevent further vascular complications. Follow-up imaging showed realignment of the atlantoaxial joint and reduction of the dissecting pseudoaneurysm of the left vertebral artery. In our patient, screening MRA has led to the discovery of asymptomatic arterial and skeletal abnormalities which, if left untreated, might have led to severe cerebrovascular complications. Therefore, AAD correction or close monitoring with MRA should be provided to MFS patients with this craniovertebral junction anomaly, even if asymptomatic.

Neurological abnormalities in individuals with Marfan syndrome: results from a genetically confirmed Italian cohort.

BACKGROUND AND AIMS: Neurological abnormalities have been frequently reported in individuals with Marfan Syndrome (MFS). However, available data relies solely on retrospective studies predating current diagnostic criteria. METHODS: Cross-sectional study comprehensively investigating neurological abnormalities within a prospective cohort of adults (≥ 18 years) with genetically confirmed MFS referred to an Italian hub center for heritable connective tissue diseases (Jan. 1st - Nov. 15th, 2021). RESULTS: We included a total of 38 individuals (53% female). The commonest neurological symptom was migraine (58%), usually without aura (73%). Neuropsychological testing was generally unremarkable, whilst anxiety and depression were highly prevalent within our cohort (42% and 34%, respectively). The most frequent brain parenchymal abnormality was the presence of cortico-subcortical hypointense spots on brain MRI T2* Gradient-Echo sequences (39%), which were found only in patients with a prior history of aortic surgery. Migraineurs had a higher frequency of brain vessels tortuosity vs. individuals without migraine (73% vs. 31%; p = 0.027) and showed higher average and maximum tortuosity indexes in both anterior and posterior circulation brain vessels (all p < 0.05). At univariate regression analysis, the presence of brain vessels tortuosity was significantly associated with a higher risk of migraine (OR 5.87, CI 95% 1.42-24.11; p = 0.014). CONCLUSIONS: Our study confirms that neurological abnormalities are frequent in individuals with MFS. While migraine appears to be associated with brain vessels tortuosity, brain parenchymal abnormalities are typical of individuals with a prior history of aortic surgery. Larger prospective studies are needed to understand the relationship between parenchymal abnormalities and long-term cognitive outcomes.

Quantitative measurement of dural ectasia: associations with clinical and genetic characteristics in Marfan syndrome.

PURPOSE: Dural ectasia (DE) may significantly impact Marfan syndrome (MFS) patients' quality of life due to chronic lower back pain, postural headache and urinary disorders. We aimed to evaluate the association of quantitative measurements of DE, and their evolution over time, with demographic, clinical and genetic characteristics in a cohort of MFS patients. METHODS: We retrospectively included 88 consecutive patients (39% females, mean age 37.1 ± 14.2 years) with genetically confirmed MFS who underwent at least one MRI or CT examination of the lumbosacral spine. Vertebral scalloping (VS) and dural sac ratio (DSR) were calculated from L3 to S3. Likely pathogenic or pathogenic FBN1 variants were categorized as either protein-truncating or in-frame. The latter were further classified according to their impact on the cysteine content of fibrillin-1. RESULTS: Higher values of the systemic score (revised Ghent criteria) were associated with greater DSR at lumbar (p < 0.001) and sacral (p = 0.021) levels. Patients with protein-truncating variants exhibited a greater annual increase in lumbar (p = 0.039) and sacral (p = 0.048) DSR. Mutations affecting fibrillin-1 cysteine content were linked to higher VS (p = 0.009) and DSR (p = 0.038) at S1, along with a faster increase in VS (p = 0.032) and DSR (p = 0.001) in the lumbar region. CONCLUSION: Our study shed further light on the relationship between genotype, dural pathology, and the overall clinical spectrum of MFS. The identification of protein-truncating variants and those impacting cysteine content may therefore suggest closer patient monitoring, in order to address potential complications associated with DE.

Staged approach for correction of anomalous venous return to the azygos vein.

Partial anomalous pulmonary venous return into the azygous vein is a rare pathological finding. We describe the case of a 28-year-old girl who had a successful staged approach to treat this rare congenital heart disease. To avoid potential connection of a systemic venous return to the left atrium, the proximal part of the azygous vein was occluded with a percutaneous approach, then the azygous vein flow was redirected into the left atrium with a surgical procedure.

Aortic arch geometry predicts outcome in patients with Loeys-Dietz syndrome independent of the causative gene.

This study aimed to investigate the potential association between imaging features and cardiovascular outcomes in patients with Loeys­Dietz syndrome (LDS). We performed a retrospective cohort study of 36 patients with LDS and described cardiovascular events and imaging data. We observed different clinical courses in patients with LDS, irrespective of the causative gene. Angular or elongated aortic arch geometry correlated with aortic dissection (R = .39, p = .02), occurrence of the first cardiovascular event before 45 years of age (R = .36, p = .03), and the number of operations (R = 0.47, p = .004), but not with age (R = −.05, p = .79) or the causative gene (R = −0.04, p = .79). Relative absences of cardiovascular events at ages 20, 40, and 60 were 100, 75, and 56%, respectively, in patients with "romanesque" aortic arches, and 74, 39, and 21%, respectively, in patients with "gothic" and "elongated" aortic arches (p = .03). Angular or elongated aortic arch geometry is associated with early­onset of disease and a worse cardiovascular outcome in LDS patients. Large multicenter studies are warranted to elucidate the impact of aortic arch morphology evaluation in clinical practice.

Dacron Conduit for Extracardiac Total Cavopulmonary Anastomosis: A Word of Caution.

BACKGROUND: The extracardiac conduit technique is a valid option for completing total cavopulmonary anastomosis (TCPC) in patients with a single ventricle. The technique allows for beating heart surgery, optimal flow dynamics, and reduced postoperative atrial arrhythmia. Different types of conduit have been proposed. This study reported a single-centre experience with two different types of conduit. METHODS: Consecutive patients referred for TCPC at the current institution between January 2001 and September 2013 were included. Retrospective extraction of pertinent variables was accomplished through electronic patient chart review. Patients were stratified based on the type of conduit used to perform the TCPC: polytetrafluoroethylene (PTFE) conduit (Group A) and polyethylene-terephthalate (Dacron) conduit (Group B). RESULTS: The patient population included 105 patients: Group A had 80 patients, and Group B had 25 patients. The two groups were similar in major clinical and procedural variables, including conduit size and Nakata index. Eighteen patients (Group A: one [1.25%]; Group B: 17 [68%]) had conduit occlusion or severe stenosis requiring intervention after a mean 46.9±35months after the operation. The percentage of patients in Group A who were free of conduit obstruction at 3, 5, and 10 years was 100%, 100%, and 96%, respectively, whereas these figures were 68%, 52%, and 35% in Group B (log-rank <0.000). Conduit re-intervention was associated with an increased risk of overall mortality after primary intervention (p<0.004). Dacron tube was found to be an independent risk factor for mid-term stenosis or obstruction (hazard ratio, 62.9; 95% CI, 8.2-482.2; p=0.000). CONCLUSION: Dacron conduit for TCPC surgery was associated with a higher risk of obstruction and need for early re-intervention compared with PTFE conduit. Surgical or percutaneous re-interventions for conduit obstruction increased the risk of late mortality.

Marfan and Loeys-Dietz aortic phenotype: A potential tool for diagnosis and management.

Objective: In heritable aortic diseases, different vascular involvement may occur with potential variable implications in aortic dilation/dissection risk. This study aimed to analyze the aortic anatomy of individuals with Marfan syndrome and Loeys-Dietz syndrome to identify possible morphological differences. Methods: Computed tomography and magnetic resonance imaging of the thoracoabdominal aorta from the proximal supra-aortic vessels to the femoral bifurcation level of 114 patients with Marfan and Loeys-Dietz syndromes and 20 matched control subjects were examined. Aortic diameters, areas, length, and tortuosity were measured in different aortic segments using specific vessel analysis software. Results: Patients with Marfan syndrome showed a higher prevalence of ascending aorta and aortic root dilation (P = .011), larger and longer aortic roots (P = .013) with pear-shaped phenotype, larger isthmus/descending aorta diameter ratio (P = .015), and larger suprarenal aorta and iliac arteries. Patients with Loeys-Dietz syndrome showed longer indexed segments and a significantly longer arch (P = .006) with type 2/3 arch prevalence (P = .097). Measurement ratios analysis provided cut-off values (aortic root to ascending aorta length/aortic root diameter, aortic root/sinotubular junction, aortic root/ascending aorta diameter) differentiating patients with Marfan syndrome from patients with Loeys-Dietz syndrome, even in the early stage of the disease. Conclusions: Both syndromes show peculiar anatomic patterns at different aortic levels irrespective of aortic dilation and disease severity. These features may represent the expression of different genetic mutations on aortic development, with a potential impact on prognosis and possibly contributing to better management of the diseases. The systematic adoption of whole body imaging with magnetic resonance or computed tomography should always be considered, because they allow a complete vascular assessment with practical indicators of differential diagnosis.

Performance and Failure of Right Ventricle to Pulmonary Artery Conduit in Congenital Heart Disease.

Surgical implantation of a right ventricle to pulmonary artery (RV-PA) conduit is an important component of congenital heart disease (CHD) surgery, but with limited durability, leading to re-intervention. The present single-center, retrospective, cohort study reports the results of surgically implanted RV-PA conduits in a consecutive series of children and adults with CHD. Patients with CHD referred for RV-PA conduit surgical implantation (from October 1997 to January 2022) were included. The primary outcome was conduit failure, defined as a peak gradient above 64 mm Hg, severe regurgitation, or the need for conduit-related interventions. Longitudinal echocardiographic studies were available for mixed-effects linear regression analysis. A total of 252 patients were initially included; 149 patients were eligible for follow-up data collection. After a median follow-up time of 49 months, the primary study end point occurred in 44 (29%) patients. A multivariable Cox regression model identified adult age (>18 years) at implantation and pulmonary homograft implantation as protective factors (hazard ratio 0.11, 95% confidence interval [CI] 0.02 to 0.47 and hazard ratio 0.34, 95% CI 0.16 to 0.74, respectively). Fever within 7 days of surgical conduit implantation was a risk factor for early (within 24 months) failure (odds ratio 4.29, 95% CI 1.41 to 13.01). Long-term use of oral anticoagulants was independently associated with slower progression of peak echocardiographic gradient across the conduits (mixed-effects linear regression p = 0.027). In patients with CHD, the rate of failure of surgically implanted RV-PA conduits is higher in children and after nonhomograft conduit implantation. Early fever after surgery is a strong risk factor for early failure. Long-term anticoagulation seems to exert a protective effect.

Thoracic aortic aneurysm in infancy in aneurysms-osteoarthritis syndrome due to a novel SMAD3 mutation: further delineation of the phenotype.

Recently, mutations in the SMAD3 gene were found to cause a new autosomal dominant aneurysm condition similar to Loeys-Dietz syndrome (LDS), mostly with osteoarthritis, called aneurysms-osteoarthritis syndrome (AOS). Our 3-year-old propositus underwent correction of an inguinal hernia at 3 months and substitution of the ascending aorta for pathologic dilation at 12 months of age. Family history reveals aortic dilation in his mother at 30 years, death due to aortic dissection of an 18-year-old maternal aunt, surgical replacement of the ascending aorta because of aneurysm in a maternal uncle at 19 years, postpartum death of the maternal grandmother at 24 years and surgical intervention because of thoracic aortic aneurysm in a brother of the propositus' grandmother at 54 years. The affected individuals present with several other signs of connective tissue disease, but the two adult patients evaluated revealed no radiologic evidence of osteoarthritis. Molecular testing of the TGFBR1 and TGFBR2 genes, involved in LDS, resulted negative, but analysis of SMAD3 disclosed the novel heterozygous loss-of-function mutation c.1170_1179del (p.Ser391AlafsX7) in exon 9 in all affected family members, confirming the diagnosis of AOS. SMAD3 mutations should be considered in patients of all ages with LDS-like phenotypes and negative TGFBR1/2 molecular tests, especially in the presence of aortic root or ascending aortic aneurysms, even though signs of early onset osteoarthritis are absent.

[Tachyarrhythmias in congenital heart disease patients: diagnosis, clinical presentation and treatment]. / Tachiaritmie nel paziente con cardiopatia congenita: diagnosi, presentazione clinica e trattamento.

Tachyarrhythmias are a major cause of morbidity and mortality in adult congenital heart disease patients. There is a strong association between tachyarrhythmias and the specific congenital heart disease and the patient's surgical history. Health care for adults with congenital heart disease and arrhythmias should be coordinated by adult congenital heart disease centers of excellence that serve as a resource for consultation and referral. A complete and multidisciplinary evaluation of patients with tachyarrhythmias, including a detailed hemodynamic and electrophysiological evaluation, is mandatory to define the best treatment strategy.

[Management of postoperative arrhythmias in the tetralogy of Fallot: a literature review]. / Gestione delle aritmie cardiache dopo correzione chirurgica della tetralogia di Fallot: revisione della letteratura.

Tetralogy of Fallot (ToF) occurs in about 4 births/1000/year and represents about one tenth of all congenital heart diseases. Nowadays 86% of patients reach adulthood with corrective surgery. Before the 1980s, these patients were treated only with "surgical palliation", which consisted in the creation of a systemic to pulmonary artery shunt or a pulmonary valvulotomy, whereas after the introduction of extracorporeal circulation, corrective surgery is performed electively between 3 and 6 months of life. After repair patients during their life may develop hemodynamic lesions, including right ventricular outflow tract dysfunction, and arrhythmias which can occur in over 30% of cases. It is estimated that these patients present a risk of sudden death of 0.2%/year. Therefore, for the prevention and treatment of arrhythmic events, a periodic follow-up in specialized centres for adult congenital heart disease is mandatory, because most often arrhythmias are triggered by the presence of hemodynamic lesions, first of all pulmonary regurgitation.

Complete Isolation of Left Innominate Artery in a Patient With CHARGE Syndrome: Case Presentation and Review of Reported Cases.

We report a rare case of complete isolation of the left innominate artery in a child with CHARGE (coloboma, heart defects, atresia choanae, growth retardation, genital abnormalities, and ear abnormalities) syndrome. This anatomical cluster had been undetected for a relatively large period of time and the patient was referred to us with an incomplete diagnosis even after multiple medical evaluations and a thoracic surgery during the neonatal period. In conclusion, to the best of our knowledge, this is the first case of a complete isolation of left innominate artery treated with a transcatheter approach.

Prevalence of unruptured intracranial aneurysms in patients with Marfan syndrome: A cross-sectional study and meta-analysis.

INTRODUCTION: Marfan syndrome (MFS) is the most common inherited connective tissue disorder and its association with intracranial aneurysms (ICAs) has been debated for more than two decades. Here, we report the prevalence of ICAs at screening neuroimaging in a population of genetically confirmed MFS patients and present the results of a meta-analysis including our cohort of patients and those of previous studies. PATIENTS AND METHODS: We enrolled 100 consecutive MFS patients, who underwent screening with brain magnetic resonance angiography at our tertiary center between August 2018 and May 2022. We did a PubMed and Web of Science search to retrieve all studies on the prevalence of ICAs in patients with MFS published before November, 2022. RESULTS: Of the 100 patients included in this study (94% Caucasians, 40% females, mean age 38.6 ± 14.6 years), three had an ICA. We pooled the current study with five previously published studies, including a total of 465 patients, 43 of which harbored at least one unruptured ICA, leading to an overall ICA prevalence of 8.9% (95% CI 5.8%-13.3%). DISCUSSION AND CONCLUSION: In our cohort of genetically confirmed MFS patients, the prevalence of ICAs was 3%, which is substantially lower compared to previous studies based on neuroimaging. The high frequency of ICA found in previous studies could be explained by selection bias and lack of genetic testing, which may have led to the inclusion of patients with different connective tissue disorders. Further studies, including several centers and a large number of patients with genetically confirmed MFS, are needed to confirm our results.

Long Term Follow-Up of Patients with Systemic Right Ventricle and Biventricular Physiology: A Single Centre Experience.

BACKGROUND: A progressively increasing prevalence of congenital heart disease (CHD) in adulthood has been noticed in recent decades; CHD cases with a systemic right ventricle have a poorer outcome. METHODS: Seventy-three patients with SRV evaluated in an outpatient clinic between 2014 and 2020 were enrolled in this study. Thirty-four patients had a transposition of the great arteries treated with an atrial switch operation; 39 patients had a congenitally corrected transposition of the great arteries (ccTGA). RESULTS: Mean age at the first evaluation was 29.6 ± 14.2 years; 48% of the patients were female. The NYHA class at the visit was III or IV in 14% of the cases. Thirteen patients had at least one previous pregnancy. In 25% of the cases, complications occurred during pregnancy. Survival free from adverse events was 98.6% at one year and 90% at 6-year follow-up without any difference between the two groups. Two patients died and one received heart transplantation during follow-up. The most common adverse event during follow-up was the presence of arrhythmia requiring hospitalization (27.1%), followed by heart failure (12.3%). The presence of LGE together with lower exercise capacity, higher NYHA class and more dilated and/or hypokinetic RV predicted a poorer outcome. Quality of life was similar to the QoL of the Italian population. CONCLUSIONS: Long-term follow-up of patients with a systemic right ventricle is characterized by a high incidence of clinical events, prevalently arrhythmias and heart failure, which cause most of the unscheduled hospitalizations.

Rationale and Design of the Multicenter Catheter Ablation of Ventricular Tachycardia Before Transcatheter Pulmonary Valve Replacement in Repaired Tetralogy of Fallot Study.

Patients with repaired tetralogy of Fallot are at elevated risk for ventricular arrhythmia and sudden cardiac death. Over the past decade, the pathogenesis and natural history of ventricular tachycardia has become increasingly understood, and catheter ablation has emerged as an effective treatment modality. Concurrently, there has been great progress in the development of a versatile array of transcatheter valves that can be placed in the native right ventricular outflow tract for the treatment of long-standing pulmonary regurgitation. Although such valve platforms may eliminate the need for repeat cardiac operations, they may also impede catheter access to the myocardial substrates responsible for sustained macro-reentrant ventricular tachycardia. This manuscript provides the rationale and design of a recently devised multicenter study that will examine the clinical outcomes of a uniform, preemptive strategy to eliminate ventricular tachycardia substrates before transcatheter pulmonary valve implantation in patients with tetralogy of Fallot.

Increased intracranial arterial tortuosity is associated with worse cardiovascular outcome in patients with Loeys-Dietz syndrome.

The aim of our study was to evaluate the association between intracranial arterial tortuosity and cardiovascular outcome in patients with Loeys-Dietz syndrome (LDS). We performed a retrospective analysis of all patients with genetically confirmed LDS who underwent at least one brain MRA at our institution (n = 32); demographic and clinical features were evaluated in relation to the tortuosity of intracranial arteries as measured by tortuosity index (TI), which was calculated using the formula: [(centerline length) / (straight-line length)-1] × 100. Receiver operating characteristic curve analysis for intracranial TI and the binary end point of aortic surgery showed vertebrobasilar TI (VBTI) to be the best classifier among the examined arterial segments (AUC = 0.822). Patients with higher VBTI showed a greater incidence of aortic surgery (p < 0.001) and underwent more surgical and endovascular procedures (p = 0.006), with a higher rate of operations (p = 0.002). Kaplan-Meier analysis showed a significantly longer surgery-free survival in patients with lower arterial tortuosity (p < 0.001). At multivariate analysis, higher VBTI was associated with an increased risk of surgery (p < 0.001), which was independent of gene mutation and patient age. Increased VBTI is a marker of adverse cardiovascular outcome in patients with LDS, which can be easily measured on brain MRA, and may be useful in the management of this heterogeneous patient population.