Autologous skeletal myoblast transplantation might improve postinfarction ventricular function, but graft viability and differentiation (ie, proof of concept) has not been shown. A 72-year-old man ...had autologous cultured myoblasts from his vastus lateralis injected to an area of transmural inferior myocardial infarction in non-reperfused scar tissue. He showed improvement in symptoms and left-ventricular ejection fraction. When he died 17·5 months after the procedure, the grafted post-infarction scar showed well developed skeletal myotubes with a preserved contractile apparatus. 65% of myotubes expressed the slow myosin isoform and 33% coexpressed the slow and fast isoforms (
vs 44% and 0·6%, respectively, in skeletal muscle). Myoblast grafts can survive and show a switch to slow-twitch fibres, which might allow sustained improvement in cardiac function.
Highlights • Flecainide unmasked conduction disorders in the DMSXL mouse model of DM1. • On action potential recording, the dV/dtmax , was lower in DMSXL mice. • Inactivation and recovery from ...inactivation of sodium current INa were faster in DMSXL myocytes. • The lower dV/dtmax was due to a 1.7 times faster rate of INa inactivation in DMSXL myocytes. • The study points the sodium current as a major component of the rhythmic phenotype in DM1.
We hypothesized that pacemaker (PM) implantation in patients with myotonic dystrophy (MD) with a prolonged HV interval, even asymptomatic, may protect them against sudden death related to ...atrioventricular (AV) block. We sought to prospectively document the true incidence of AV block episodes in this high-risk population and accurately trace, in the long term, by the PM, the occurrence of arrhythmias that may remain undetected during conventional follow-up.
Myotonic dystrophy is associated with a high risk of sudden death, commonly attributed to AV block or ventricular arrhythmias, but cardiac pacing is only recommended as a secondary prevention.
Patients with MD with an HV interval > or =70 ms, even in the absence of related symptoms, prospectively received a cardiac PM, including an algorithm capable of diagnosing episodes of bradycardia and tachyarrhythmias.
The population consisted of 49 patients (45.5 +/- 8.9 years old) followed for 53.5 +/- 27.2 months. Paroxysmal arrhythmias were recorded in 41 patients (83.7%), consisting of complete AV block (n = 21), sino-atrial block (n = 4), or atrial (n = 25) or ventricular (n = 13) tachyarrhythmias. No patient died of AV block during follow-up, but 10 deaths occurred, 4 of them sudden. An arrhythmic cause could be excluded by postmortem PM interrogation in two cases of typical sudden death.
Arrhythmias are common in patients with MD with infrahisian conduction abnormalities. The prophylactic implantation of a pacing system when the HV interval is > or =70 ms seems appropriate. The PM protects the patient against the clinical consequences of paroxysmal profound bradycardia and facilitates the diagnosis and management of frequent paroxysmal tachyarrhythmias.
•For families, there is no ‘pre-symptomatic’ phase once dystrophinopathy is diagnosed.•A care-coordinator facilitated, multi-specialty adult follow-up model is advocated.•Hearts of patients with DMD ...should be considered abnormal ‘from the start’.•Ventricular dysfunction is preceded by changes, detectable by cardiac MR-imaging.•A patient's phenotype and not genotype should guide clinical decision-making.
Background: Heart failure (HF) with a preserved left ventricular (LV) ejection fraction (EF) is the leading cause of hospitalization after 65 years of age. Individual randomized trials have not shown ...benefits conferred by angiotensin-converting enzyme (ACE) inhibitors or angiotensin-II receptor blockers (ARB) in these patients. To overcome this limitation, we performed a meta-analysis of the randomized trials of ACE inhibitors or ARB in patients with HF and preserved LVEF. Methods: Our search identified 4 randomized trials, comprising a total of 8152 patients, that investigated the effects of ACE inhibitors (n = 1), ARB (n = 2), or both treatments (n = 1). Risk ratios (RR) and 95% confidence intervals (CI) were calculated using a fixed-effect estimate method in the randomised trials. Results: Compared with placebo or no treatment, treatment with ACE inhibition or ARB was associated with lower rates of hospitalization for HF (RR 0.90; 95% CI 0.81-0.99, P = .032), though not cardiovascular mortality (RR 1.01; 95% CI 0.90-1.13, P = 0.858). In 3 studies where these endpoints were combined, the 1-year incidence of cardiovascular death or hospitalization for HF was lowered by ACE inhibition or ARB (RR 0.74; 95% CI 0.58-0.94, P = .014). Conclusion: Compared with placebo, ACE inhibition or ARB significantly lowered risks of (a) hospitalization for HF and (b) the combined endpoint of cardiovascular mortality and hospitalization for HF at 1 year, in patients with HF and preserved LVEF. However, they have no significant effect on mortality during more prolonged follow-up; the width of the 95% confidence limits is compatible with a benefit as big as 10% or a hazard as large as 13%.
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.
Highlights • We retrospectively studied 131 French late onset Pompe disease patients (LOPD). • 4 patients needed pacemaker implantation for severe atrio-ventricular blocks. • In patients presenting ...with atrio-ventricular blocks, echocardiography was normal. • These patients had no risk factors for cardiovascular diseases. • Cardiac follow-up in PD patients should include periodic EKG and Holter-EKG monitoring.
To describe the incidence and identify predictors of sudden death (SD), major conduction defects and sustained ventricular tachyarrhythmias (VTA) in myotonic dystrophy type 1 (DM1).
We ...retrospectively enrolled 1388 adults with DM1 referred to six French medical centres between January 2000 and October 2013. We confirmed their vital status, classified all deaths, and determined the incidence of major conduction defects requiring permanent pacing and sustained VTA. We searched for predictors of overall survival, SD, major conduction defects, and sustained VTA by Cox regression analysis. Over a median 10-year follow-up, 253 (18.2%) patients died, 39 (3.6%) suddenly. Analysis of the cardiac rhythm at the time of the 39 SD revealed sustained VTA in 9, asystole in 5, complete atrioventricular block in 1 and electromechanical dissociation in two patients. Non-cardiac causes were identified in the five patients with SD who underwent autopsies. Major conduction defects developed in 143 (19.3%) and sustained VTA in 26 (2.3%) patients. By Cox regression analysis, age, family history of SD and left bundle branch block were independent predictors of SD, while age, male sex, electrocardiographic conduction abnormalities, syncope, and atrial fibrillation were independent predictors of major conduction defects; non-sustained VTA was the only predictor of sustained VTA.
SD was a frequent mode of death in DM1, with multiple mechanisms involved. Major conduction defects were by far more frequent than sustained VTA, whose only independent predictor was a personal history of non-sustained VTA. ClinicalTrials.gov no: NCT01136330.
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