Prevalence and Complications of Aberrant Subclavian Artery in Patients With Heritable and Nonheritable Arteriopathies.

BACKGROUND: An aberrant subclavian artery (ASA) (or lusoria) is the most common congenital anomaly of the aortic arch (0.5%-2.2%; female-to-male ratio 2:1 to 3:1). ASA can become aneurysmal and result in dissection, involving Kommerell's diverticulum when present and the aorta. Data of its significance in genetic arteriopathies are not available. OBJECTIVES: The purpose of this study was to assess the prevalence and complications of ASA in gene-positive and -negative nonatherosclerotic arteriopathies. MATERIALS: The series includes 1,418 consecutive patients with gene-positive (n = 854) and gene-negative arteriopathies (n = 564) diagnosed as part of institutional work-up for nonatherosclerotic syndromic and nonsyndromic arteriopathies. Comprehensive evaluation includes genetic counseling, next-generation sequencing multigene testing, cardiovascular and multidisciplinary assessment, and whole-body computed tomography angiography. RESULTS: ASA was found in 34 of 1,418 cases (2.4%), with a similar prevalence in gene-positive (n = 21 of 854, 2.5%) and gene-negative (n = 13 of 564, 2.3%) arteriopathies. Of the former 21 patients, 14 had Marfan syndrome, 5 had Loeys-Dietz syndrome, 1 had type-IV Ehlers-Danlos syndrome, and 1 had periventricular heterotopia type 1. ASA did not segregate with genetic defects. Dissection occurred in 5 of 21 patients with genetic arteriopathies (23.8%; 2 Marfan syndrome and 3 Loeys-Dietz syndrome), all with associated Kommerell's diverticulum. No dissections occurred in gene-negative patients. At baseline, none of the 5 patients with ASA dissection fulfilled criteria for elective repair according to guidelines. CONCLUSIONS: The risk of complications of ASA is higher in patients with genetic arteriopathies and is difficult to predict. In these diseases, imaging of the supra-aortic trunks should enter baseline investigations. Determination of precise indications for repair can prevent unexpected acute events such as those described.

Genetics and clinics: together to diagnose cardiomyopathies.

The diagnostic paths of hereditary cardiomyopathies (CMPs) include both clinical and molecular genetics. The first step is the clinical diagnosis that guides the decisions about treatments, monitoring, prognostic stratification, and prevention of major events. The type of CMP [hypertrophic cardiomyopathy, dilated cardiomyopathy, restrictive cardiomyopathy, and arrhythmogenic right ventricular cardiomyopathy (ARVC)] is defined by the phenotype, and the genetic testing may identify the precise cause. Furthermore, genetic testing provides a pre-clinical diagnosis in unaffected family members and the basis for prenatal diagnosis. It can contribute to risk stratification (e.g. LMNA) and can be a major diagnostic criterion (e.g. ARVC). The test can be limited to a single gene when the pre-test diagnostic hypothesis is based on proven clinical evidence (e.g. GLA for Fabry disease). Alternatively, it can be expanded from a multigene panel to a whole exome or whole genome sequencing when the pre-test hypothesis is a genetically heterogeneous disease. In the last decade, the study of larger genomic targets led to the identification of numerous gene variants not only pathogenic (clinically actionable) but also of uncertain clinical significance (not actionable). For the latter, the pillar of the genetic diagnosis is the correct interpretation of the pathogenicity of genetic variants, which is evaluated using both bioinformatics and clinical-genetic criteria about the patient and family. In this context, cardiologists play a central role in the interpretation of genetic tests, performing the deep-phenotyping of variant carriers and establishing the co-segregation of the genotype with the phenotype in families.

Long COVID: long-term effects?

The term Long COVID (or Post COVID) describes a condition characterized by persistence of symptoms for at least 12 weeks after the onset of COVID-19. It may last several months but the duration is still matter of observation. The symptoms and the clinical manifestations are clinically heterogeneous and suggesting involvement of multi-organs/systems, including the cardiovascular system. The general recurrent symptoms include fatigue, breathlessness, myalgia, headache, loss of memory, and impaired concentration. Patients report loss of their previous psychophysical performance. Cardiovascular involvement manifests with common symptoms such as palpitations and chest pain, and, less commonly, with events such as late arterial and venous thromboembolisms, heart failure episodes, strokes or transient ischaemic attack, 'myo-pericarditis'. The diagnostic criteria are mainly based on the narrative of the patients. Measurable biomarkers or instrumental findings or clinical events are not yet framed in a shared diagnostic framework. The open question for clinicians and researchers is whether biomarkers, electrocardiogram, non-invasive imaging, and clinical monitoring should be included in a shared diagnostic protocol aimed at defining the diagnostic path and protecting patients at risk of unexpected events.

A case series of CHARGE syndrome: identification of key features for a neonatal diagnosis.

BACKGROUND: An early diagnosis of CHARGE syndrome is challenging, especially for the primary care physicians who often take care of neonates with multiple congenital anomalies. Here we report eight cases of CHARGE syndrome whose diagnosis was made early in life with the intent to identify the most helpful features allowing a prompt clinical diagnosis. METHODS: Medical records of patients with CHARGE syndrome whose diagnosis was made at the Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico in Milan, Italy were retrospectively reviewed. RESULTS: Taken together, these patients reflect the considerable phenotypic variability of the syndrome; in one patient, the diagnosis was made immediately after birth because all the major criteria were met. In six patients, presenting with relatively nonspecific defects, a temporal bone computerized tomography scan was essential to achieve the correct diagnosis. In one patient, the diagnosis was made later than the others were. A careful examination revealed the presence of outer, middle, and inner ear anomalies: these elements, in the absence of any additional major criteria, represented for us an important diagnostic clue. CONCLUSIONS: This article suggests that an accurate evaluation of the ear should be made every time CHARGE syndrome is considered as a likely diagnosis even when the standard criteria are not fulfilled.