Mutations in PRKAG2, the gene encoding for the γ2 subunit of 5'-AMP-activated protein kinase (AMPK), are responsible for an autosomal dominant glycogenosis with a cardiac presentation, associating ...hypertrophic cardiomyopathy (HCM), ventricular pre-excitation (VPE), and progressive heart block. The aim of this study was to perform a retrospective time-to-event study of the clinical manifestations associated with PRKAG2 mutations.
A cohort of 34 patients from 9 families was recruited between 2001 and 2010. DNA were sequenced on all exons and flanking sequences of the PRKAG2 gene using Sanger sequencing. Overall, four families carried the recurrent p.Arg302Gln mutation, and the five others carried private mutations among which three had never been reported. In the total cohort, at 40 years of age, the risk of developing HCM was 61%, VPE 70%, conduction block 22%, and sudden cardiac death (SCD) 20%. The global survival at 60 years of age was 66%. Thirty-two per cent of patients (N = 10) required a device implantation (5 pacemakers and 5 defibrillators) at a median age of 66 years, and two patients required heart transplant. Only one patient presented with significant skeletal muscle symptoms. No significant differences regarding the occurrence of VPE, ablation complications, or death incidence were observed between different mutations.
This study of patients with PRKAG2 mutations provides a more comprehensive view of the natural history of this disease and demonstrates a high risk of cardiac complications. Early recognition of this disease appears important to allow an appropriate management.
The prevalence of arterial hypertension in mitochondrial diseases remains unknown. Between January 2000 and May 2014, we retrospectively included patients with genetically proven mitochondrial ...diseases. We recorded clinical, genetic and cardiac exploration data, including the measure of arterial pressure. Among the 260 patients included in the study (mean age = 44 ± 15 years, women = 158), 108 (41.5%) presented with arterial hypertension. The prevalence of hypertension by sex and age was higher than that observed in the general population for all groups. The prevalence of hypertension was significantly higher in patients with MELAS (mitochondrial encephalopathy, lactic acidosis, and stroke‐like episodes) mutations (66%) and MERRF (myoclonus, epilepsy, ataxia with ragged ref fibres) mutations (61%). In patients with MELAS mutation, the presence of hypertension was significantly associated with age and mutation rate in the blood (odds ratio = 1.12; P = .02) in multivariate analysis. The prevalence of hypertension was more important in patients having a mitochondrial disease. The increased risk was more important in patient with MELAS or MERRF and depended on the rate of heteroplasmy.
To assess the follow-up of patients with sarcoidosis and myocardial MRI abnormalities.
Twelve patients with histologically proven sarcoidosis and highly suspected cardiac involvement underwent ...initial and 12-month follow-up cardiac assessment including cardiac MRI (T2-weighted, functional gradient echo, and T1-weighted gadolinium-diethylenetriamine penta-acetic acid-enhanced sequences). MRI abnormalities and clinical and MRI progression were scored by two observers.
Six patients receiving corticosteroid therapy (including three patients with clinical cardiac involvement) were scored as having cleared or improved at MRI follow-up, while others were seen to have worsened or remained stable. The stability, improvement, or clearing of MRI findings were correlated with clinically stable, improved or cleared sarcoidosis, while a worsening at MRI follow-up was correlated with a worsening of sarcoidosis and, in one patient, was predictive of clinical cardiac involvement.
Cardiac MRI is a useful noninvasive method for the early diagnosis and follow-up of cardiac sarcoidosis.
Myoblast transplantation for heart failure Menasché, Philippe; Hagège, Albert A; Scorsin, Marcio ...
The Lancet (British edition),
01/2001, Letnik:
357, Številka:
9252
Journal Article
Recenzirano
Intramyocardial skeletal muscle transplantation has been shown experimentally to improve heart function after infarction. We report success with this procedure in a patient with severe ischaemic ...heart failure. We implanted autologous skeletal myoblasts into the postinfarction scar during coronary artery bypass grafting of remote myocardial areas. 5 months later, there was evidence of contraction and viability in the grafted scar on echocardiography and positron emission tomography. Although this result is encouraging, it requires validation by additional studies.
Skeletal myoblast (SM) transplantation (Tx) in a post-myocardial infarction (MI) scar experimentally improves left ventricular (LV) ejection fraction (EF). Short-term follow-up (FU) studies have ...suggested that a similar benefit could clinically occur despite an increased risk of LV arrhythmias.
We report the long-term FU of the first worldwide cohort of grafted patients (n = 9, 61.8+/-11.6 years, previous MI, EF < or = 35%) operated on (autologous SM Tx and bypass surgery) in 2000 to 2001 and evaluated before Tx, at 1 month (M1) and at a median FU of 52 (18 to 58) months after Tx (37 patient-years). NYHA class improved from 2.5+/-0.5 to 1.8+/-0.4 at M1 (P=0.004 versus baseline) and 1.7+/-0.5 at FU (P=not significant versus M1; P=0.0007 versus baseline). EF increased from 24.3+/-4% to 31+/-4.1% at M1 (+28%, P=0.001 versus baseline) and remained stable thereafter (28.7+/-8.1%, +18% versus baseline). There were 5 hospitalizations for heart failure in 3 patients at 28.6+/-9.9 months, allowing implant in 2 patients with a resynchronization pacemaker. An automatic cardiac defibrillator (ACD) was implanted in 5 patients for nonsustained (n =1) or sustained (n =4) ventricular tachycardia at 12.2+/-18.6 (1 to 45) months. Despite a beta-blocker/amiodarone combination therapy, there were 14 appropriate shocks for 3 arrhythmic storms in 3 patients at 6, 7, and 18 months after ACD implantation.
In this cohort of severe heart failure patients both clinical status and EF stably improve over time with a strikingly low incidence of hospitalizations for heart failure (0.13/patient-years) and the arrhythmic risk can be controlled by medical therapy and/or on-request ACD implantation.
In myotonic dystrophy type 1, the association between mutation size (CTG expansion) and the severity of cardiac involvement is controversial.
We selected 855 patients with myotonic dystrophy type 1 ...(women, 51%; median age, 37 years), with genetic testing performed at the moment of their initial cardiac evaluation, out of 1014 patients included in the Myotonic Dystrophy Type 1-Heart Registry between January 2000 and December 2015. We studied the association between CTG expansion size and other baseline characteristics and (1) cardiac involvement at baseline and (2) the incidence of death, sudden death, and other cardiac adverse events. At initial presentation, the median CTG expansion size was 530 (interquartile range, 300-830). In multivariate analysis, larger expansions were associated with the presence at baseline of conduction defects on the ECG and left ventricular systolic dysfunction. In a median 11.5 years of follow-up period, 210 patients died (25%), including 32 suddenly (4%). Supraventricular arrhythmias developed over lifetime in 166 patients (19%), sustained ventricular tachyarrhythmias in 17 (2%), and permanent pacemakers were implanted in 181 (21%). In Cox regression analyses, larger CTG expansions were significantly associated with (1) total death, sudden death, and pacemaker implantation in a model, including CTG expansion size, age, sex, diabetes mellitus, and (2) all end points except sudden death in a model including all baseline characteristics.
The size of the CTG expansion in the blood of myotonic dystrophy type 1 patients is associated with total and sudden deaths, conduction defects, left ventricular dysfunction, and supraventricular arrhythmias.
URL: https://www.clinicaltrials.gov. Unique Identifier: NCT01136330.
Highlights • We assessed management of respiratory involvement in the EU, US and Canada. • We agreed on a preliminary respiratory symptom check-list for patients with DM. • We agreed on a screening ...protocol for chronic respiratory insufficiency in DM. • We identified preliminary criteria for launching of non-invasive ventilation in DM. • We agreed and presented an initial protocol for secretion management in DM.
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