Les myxomes cardiaques sont des tumeurs bénignes généralement sporadiques. Les formes familiales, plus rares, sont associées au complexe de Carney (CNC). Une mutation germinale de PRKAR1A, codant ...pour la sous-unité régulatrice R1a de la PKA, est retrouvée chez 62 % des patients CNC et 83 % si ces derniers ont un myxome cardiaque parmi leurs atteintes. Objectif Évaluer la prévalence des mutations germinales de PRKAR1A dans les myxomes cardiaques isolés sporadiques. Patients et méthodes Quarante-huit patients majeurs ayant été opérés de myxome cardiaque, ont participé à l’étude. Une consultation spécialisée s’assurait de la présentation sporadique et isolée, et du prélèvement sanguin. L’ensemble des séquences transcrites du gène PRKAR1A a été étudié par séquençage direct et la recherche de grandes délétions par MLPA. Résultats La population étudiée est similaire à une population de myxomes sporadiques : une prédominance féminine (29F, sexe ratio 1,5), un âge moyen de 61,5 ans (± 11,2, range 31–89) et les myxomes sont principalement de l’oreillette gauche (84 %). Une variation faux-sens est retrouvée chez un patient de 50 ans p.Arg74His (c.221G>A) ; cet acide aminé est porteur d’une mutation faux-sens pathogène publiée p.Arg74Cys (Veugelers PNAS 2004). Une variation intronique proche du site de splice non connue comme SNP, est découvert chez deux patients (c.552-18A > G). Discussion Les mutations classiques du CNC semblent absentes dans le myxome isolé de l’adulte, en l’absence de tout élément clinique évocateur de CNC. Cependant, des variants dont la pathogénicité reste à étudier sur le plan fonctionnel sont mis en évidence.
Churg-Strauss syndrome (CSS) cardiac involvement is associated with a poor prognosis. Recently cardiac MRI (CMRI) has emerged as a promising technique to detect early CSS cardiac involvement. ...However, CMRI-detected myocardial delayed enhancement (MDE) could correspond to fibrosis or inflammation. Fluoro-2-deoxyglucose PET (FDG-PET) was previously used in other systemic diseases to distinguish between them. To determine whether the CMRI-MDE detected in CSS patients reflected fibrosis or myocardial inflammation, patients in CSS remission underwent FDG-PET.
Twenty consecutive CSS patients in remission (BVAS = 0) were recruited. Fourteen patients eight men, six women; mean (S.D.) age 49 (9) years; mean disease duration 3.5 (2.9) years with CMRI-detected MDE, and six patients four men, two women; mean (S.D.) age 44 (15) years; mean disease duration 3.5 (5.3) years with normal CMRI underwent FDG-PET. Segments with MDE on CMRI were analysed on FDG-PET images, with myocardial FDG hypofixation defining fibrosis and hyperfixation corresponding inflammation.
Among the 14 patients with MDE on CMRI, FDG-PET showed 10 had hypofixation, 2 had hyperfixation and 2 had normal scans. CSS duration at the time of CMRI was shorter for patients with myocardial inflammation than in those with fibrosis. The six patients with normal CMRI had normal FDG-PET images.
For CSS patients in remission, CMRI detected subclinical active myocardial lesions and could be recommended to assess cardiac involvement. However, because CMRI-detected MDE can reflect fibrosis or inflammation, FDG-PET might help to distinguish between the two.
Background and purpose
Our aim was to determine the prognostic value of urine and blood heteroplasmy in patients with the m.3243A>G mutation.
Methods
Adults with the m.3243A>G mutation referred to ...our institution between January 2000 and May 2014 were retrospectively included. The relationship between their baseline clinical characteristics, their mutation load in urine and blood, and major adverse events (MAEs) during follow‐up, defined as medical complications requiring a hospitalization or complicated by death, was studied.
Results
Of the 43 patients (age 45.6 ± 13.3 years) included in the study, 36 patients were symptomatic, including nine with evidence of focal brain involvement, and seven were asymptomatic. Over a 5.5 ± 4.0 year mean follow‐up duration, 14 patients (33%) developed MAEs. Patients with MAEs had a higher mutation load than others in urine (60.1% ± 13.8% vs. 40.6% ± 26.2%, P = 0.01) and in blood (26.9% ± 18.4% vs. 16.0% ± 12.1%, P = 0.03). Optimal cutoff values for the prediction of MAEs were 45% for urine and 35% for blood. In multivariate analysis, mutation load in urine ≥45% odds ratio 25.3; 95% confidence interval (CI) 1.1–567.8; P = 0.04, left ventricular hypertrophy (odds ratio 16.7; 95% CI 1.3– 222.5; P = 0.03) and seizures (odds ratio 48.3; 95% CI 2.5–933; P = 0.01) were associated with MAEs.
Conclusions
Patients with the m.3243A>G mutation are at high risk of MAEs, which can be independently predicted by mutation load in urine ≥45%, a personal history of seizures, and left ventricular hypertrophy.
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Rationnel La maladie de Steinert (DM1) est une maladie systémique associée à un risque élevé de mort subite en rapport avec des troubles conductifs et des arythmies ventriculaires. Le mécanisme de ...ces morts subites n’est pas connu. Notre objectif était de déterminer si le syndrome de Brugada est impliqué dans ces complications. Méthode Nous avons analysé les électrocardiogrammes de 500 patients atteints de maladie de Steinert. Les patients ayant un tracé ECG avec un Brugada de type 1 ont bénéficié d’un séquençage du gène SCN5A et d’un bilan cardiaque comprenant un holter ECG, une échocardiographie et une exploration électrophysiologique. Résultats Un ECG avec un aspect de Brugada de type 1 a été identifié chez 7 patients, soit une prévalence 80 fois plus élevée que dans la population générale. Le séquençage de SCN5A était normal chez tous les patients. Un patient a fait une mort subite en rapport avec une fibrillation ventriculaire et la stimulation ventriculaire programmée a déclenché des tachycardies ventriculaires polymorphes chez 5 patients. Conlusion La prévalence du syndrome de Brugada est plus élevée chez les patients DM1 que dans la population générale. Les patients présentant l’association de ces deux anomalies semblent exposés à un risque élevé d’arythmies ventriculaires sévères.
Emery‐Dreifuss muscular dystrophy (EDMD) is characterized by early contractures of the elbows and Achilles tendons, slowly progressive muscle wasting and weakness, and life‐threatening cardiomyopathy ...with conduction blocks. We recently identified LMNA encoding two nuclear envelope proteins, lamins A and C, to be implicated in the autosomal dominant form of EDMD. Here, we report on the variability of the phenotype and spectrum of LMNA mutations in 53 autosomal dominant EDMD patients (36 members of 6 families and 17 sporadic cases). Twelve of the 53 patients showed cardiac involvement exclusively, although the remaining 41 all showed muscle weakness and contractures. We were able to identify a common phenotype among the patients with skeletal muscle involvement, consisting of humeroperoneal wasting and weakness, scapular winging, rigidity of the spine, and elbow and Achilles tendon contractures. The disease course was generally slow, but we observed either a milder phenotype characterized by late onset and a mild degree of weakness and contractures or a more severe phenotype with early presentation and a rapidly progressive course in a few cases. Mutation analysis identified 18 mutations in LMNA (ie, 1 nonsense mutation, 2 deletions of a codon, and 15 missense mutations). All the mutations were distributed between exons 1 and 9 in the region of LMNA that is common to lamins A and C. LMNA mutations arose de novo in 76% of the cases; 2 of these de novo mutations were typical hot spots, and 2 others were identified in 2 unrelated cases. There was no clear correlation between the phenotype and type or localization of the mutations within the gene. Moreover, a marked inter‐ and intra‐familial variability in the clinical expression of LMNA mutations exists, ranging from patients expressing the full clinical picture of EDMD to those characterized only by cardiac involvement, which points toward a significant role of possible modifier genes in the course of this disease. In conclusion, the high proportion of de novo mutations together with the large spectrum of both LMNA mutations and the expression of the disease should now prompt screening for LMNA in familial and sporadic cases of both EDMD and dilated cardiomyopathy associated with conduction system disease. Ann Neurol 2000;48:170–180
Abstract Background Homozygous mutations in ANO5 , a gene encoding anoctamin 5, a putative calcium-activated chloride channel, have recently been reported in patients with adult-onset myopathies or ...isolated high-CK levels. Cardiomyopathy has not previously been reported in these populations despite a proven expression of anoctamin 5 in the cardiac muscle. Methods Patients presenting for the management of high-CK levels or overt myopathy with proven ANO5 mutations were prospectively investigated between June 2010 and March 2012 in Pitié Salpêtrière Hospital, according to a standardised protocol. Neurological and cardiological clinical examinations, CK assessment, electrocardiogram (ECG), and echocardiography were performed, as well as cardiac MRI and coronary CT angiography in patients with left ventricular (LV) dysfunction. Results Our study included 19 consecutive patients (male = 15, age = 46.2 ± 12.7 years) from 16 families. Five had asymptomatic high-CK levels and 14 had overt myopathy. One patient had a personal history of stable coronary artery disease with normal ventricular function. ECG showed ventricular premature beats in one patient. Echocardiography displayed LV dilatation in two patients, LV dysfunction in one, and both abnormalities in two who fulfilled criteria for dilated cardiomyopathy which was confirmed by cardiac MRI and normal CT angiography. Conclusions Dilated cardiomyopathy is a potential complication in patients with myopathies due to mutations in the ANO5 gene whose screening requires specific procedures.
Abstract Peripartum cardiomyopathy (PPCM) is a rare disorder in which left ventricular systolic dysfunction and symptoms of heart failure occur in the peripartum period. Although cardiac magnetic ...resonance (CMR) is largely used for diagnosis and prognosis assessment in cardiomyopathies, its interest in PPCM is unknown. We reported two cases of patients with PPCM who underwent CMR. One patient had no CMR abnormality, while the second patient had several areas of myocardial delayed enhancement (MDE) on CMR images. During follow up, the patient with normal CMR was asymptomatic and had full recovery of cardiac function, whereas the patient with MDE was still symptomatic with persistence of a left ventricular dysfunction. CMR could have prognosis value in PPCM as demonstrated in other cardiomyopathies.
Background: Cardiac involvement in idiopathic inflammatory myopathy has been recognised as an important prognostic factor, but treatment remains empirical. Objective: To investigate the effects of ...corticosteroids and immunosuppressors on myocarditis in patients with inflammatory myopathies. Methods: Patients with inflammatory myositis of recent onset who had not received treatment were evaluated for associated myocarditis by magnetic resonance imaging (MRI) and reinvestigated after treatment with high dose corticosteroids and immunosuppressors. Results: Four patients with histologically proven myositis were included. Two patients with polymyositis had cardiac clinical symptoms. Two other patients with dermatomyositis and diffuse cutaneous systemic sclerosis-polymyositis overlap syndrome were asymptomatic. In three cases the usual conventional screening tests were normal. For all patients an area of contrast enhancement and hypokinesia detected by cardiac MRI was markedly reduced after treatment with corticosteroids and immunosuppressors for 6 months. Conclusion: Treatment with intravenous methylprednisolone followed by prednisone and immunosuppressive therapy seems to be effective for treating myocardial involvement in patients with idiopathic inflammatory myopathies, either alone or presenting as overlap syndromes. Cardiovascular MRI is a non-invasive technique that may be a powerful tool for diagnosis and monitoring of myocardial inflammation in this setting.
Cardiac complications, such as myocardial disease and arrhythmias, are frequent and may be severe in patients with mitochondrial disease. We sought to determine the prevalence and the prognostic ...value of cardiac abnormalities in a series of patients carrying the m.8344 A>G mutation.
We retrospectively collected data concerning a cohort of patients carrying the m.8344A>G mutation. Patients systematically underwent neurologic examination, muscular biopsy, measurement of forced vital capacity, and cardiac evaluation including electrocardiogram, echocardiography, and 24-hour ambulatory electrocardiogram at diagnosis. Neurologic and cardiac evaluations were repeated during follow-up at least every 2 years.
Eighteen patients (mean age 39.3 +/- 17.3 years, 10 women) from 8 families were investigated. Mean follow-up duration was 5.0 +/- 2.7 years. Cardiac abnormalities were identified at diagnosis in 8 patients (44.4%, age 39.1 +/- 17.7 years), including dilated cardiomyopathy in 4, Wolff-Parkinson-White syndrome in 3, incomplete left bundle branch block in 1, and ventricular premature beats in 1. Two additional patients developed left ventricular dysfunction during follow-up and 2 patients died due to heart failure. Subgroup analyses identified early age at disease onset as the only factor significantly associated with myocardial dysfunction.
We identified a high prevalence of ventricular dysfunction and Wolff-Parkinson-White syndrome. Myocardial involvement was associated with an increased risk of cardiac death due to heart failure, suggesting that cardiac investigations should be systematically considered in patients carrying the m.8344A>G mutation.
Background: Primary myocardial involvement due to microcirculation impairment is common in systemic sclerosis (SSc). Cardiovascular magnetic resonance imaging (MRI) and tissue Doppler ...echocardiography (TDE) were recently shown to be more sensitive than conventional methods for the respective assessment of myocardial perfusion and contractility. Previous studies have suggested that dihydropyridine-type calcium channel blockers mitigate both myocardial perfusion and function abnormalities. Objective: To investigate the effects of nifedipine on myocardial perfusion by MRI and on contractility by TDE, in patients with SSc. Patients and methods: 18 patients with SSc without clinical heart failure and with normal pulmonary arterial pressure (14 women, 4 men; mean (SD) age 59 (9) years; mean (SD) disease duration 7 (4) years, 10 with diffuse and 8 with limited cutaneous forms) were prospectively evaluated. The MRI perfusion index, determined from time-intensity curves, and systolic and diastolic strain rate determined by TDE were assessed at baseline, after a 72 hour vasodilator washout period, and after 14 days of oral treatment with nifedipine 60 mg/day. Results: Nifedipine treatment led to a significant increase in the MRI perfusion index (mean (SD) 0.26 (0.07) v 0.19 (0.05) at baseline, p = 0.0003) and in systolic and diastolic strain rate (2.3 (0.6) v 1.5 (0.4) s−1 at baseline, p = 0.0002, and 4.2 (1.6) v 3.0 (1.2) at baseline, p = 0.0003, respectively). Conclusion: Fourteen days of treatment with nifedipine simultaneously improves myocardial perfusion and function, as evaluated by highly sensitive and quantitative methods.
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