Loredana Messano

Risk of arrhythmias in myotonic dystrophy: trial design of the RAMYD study.

Objective Myotonic dystrophy type 1 (DM1) is the most frequent muscular dystrophy in adults. DM1 is a multisystem disorder also affecting the heart with an increased incidence of sudden death, which has been explained with the common impairment of the conduction system often requiring pacemaker implantation; however, the occurrence of sudden death despite pacemaker implantation and the observation of major ventricular arrhythmias generated the hypothesis that ventricular arrhythmias may play a causal role as well. The aim of the study was to assess the 2-year cumulative incidence and the value of noninvasive and invasive findings as predictive factors for sudden death, resuscitated cardiac arrest, ventricular fibrillation, sustained ventricular tachycardia and severe sinus dysfunction or high-degree atrioventricular block. Methods/design More than 500 DM1 patients will be evaluated at baseline with a clinical interview, 12-lead ECG, 24-h ECG and echocardiogram. Conventional and nonconventional indications to electrophysiological study, pacemaker, implantable cardioverter defibrillator or loop recorder implantation have been developed. In the case of an indication to electrophysiological study, pacemaker, implantable cardioverter defibrillator or loop recorder implant at baseline or at follow-up, the patient will be referred for the procedure. At the end of 2-year follow-up, all candidate prognostic factors will be tested for their association with the endpoints. Trial registration: ClinicalTrials.gov ID NCT00127582. Conclusion The available evidence supports the hypothesis that both bradyarrhythmias and tachyarrhythmias may cause sudden death in DM1, but the course of cardiac disease in DM1 is still unclear. We expect that this large, prospective, multicenter study will provide evidence to improve diagnostic and therapeutic strategies in DM1.

Safety and Feasibility of Coronary Sinus Left Ventricular Leads Extraction: A Preliminary Report

Background: transvenous positioning of the left ventricular (LV) lead in a branch of the coronary sinus (CS) is generally the preferred implantation technique in biventricular pacing. Very few data are reported about removal of LV pacing leads positioned in a CS branch. Aim of the study was to describe our experience with percutaneous extraction of LV pacing leads in order to evaluate feasibility and safety of this procedure.Methods: we enrolled 392 patients who underwent a biventricular pacing implant. The indication for catheter removal was considered in case of definite diagnosis of infection and in some cases of lead dislodgement or diaphragmatic stimulation. LV lead extraction was first attempted by manual traction; in case of failure a locking stylet or locking stylet plus radiofrequency could be used.Results: twelve of 392 patients implanted needed LV lead removal. The leads had been in place for 13.9 ± 11.7 months. Extraction was indicated in 5 of them for LV lead dislodgement or diaphragmatic stimulation, and in 7 patients for lead infection. In all cases manual traction succeeded to remove the LV lead. In 7 cases of infection, the right atrial and ventricular leads were removed. The mean total procedure time was 69 ± 22 min. No complications were observed.Conclusions: our study suggests that CS leads could be easily and safely removed without any complication, also when placed in a CS branch, at least for relatively young catheters.

A Randomized Comparison of Alternative Techniques to Achieve Coronary Sinus Cannulation During Biventricular Implantation Procedures

AbstractIntroduction: Biventricular pacing system implantation is a time-consuming and challenging procedure. A critical step in biventricular pacemaker implantation is coronary sinus (CS) cannulation. CS cannulation can be achieved either using dedicated guiding catheters (guiding catheter alone positioning strategy, GCA) or with the aid of an electrophysiology catheter advanced inside the guiding catheter (electrophysiology catheter aided positioning strategy, EPA). Aim of the study: To evaluate whether the EPA technique is useful for reducing CS cannulation time compared to a conventional GCA technique. Methods: Thirty-four consecutive patients were randomly assigned to the GCA (18 patients) or EPA (16 patients) CS cannulation strategy. Results: Time to successful catheterization of CS was 5.0 ± 2.4 min in the EPA group versus 10.1 ± 5.4 min in the GCA group p = 0.004. Fluoroscopy time was 4.6 ± 2.3 min in the EPA group versus 9.2 ± 4.9 min in the GCA group p = 0.004. Total contrast dye volume to search and engage the CS ostium was 0.0 ml in the EPA group versus 14.3 ± 3.4 ml in the GCA group p < 0.001. Conclusions: Cannulation of CS with the adjunct of an electrophysiology catheter to dedicated delivery systems significantly reduces procedural time, fluoroscopy time and contrast dye volume compared to a conventional strategy.

Increased platelet sodium–hydrogen exchanger activity in patients with variant angina

The causes of coronary artery spasm in patients with variant angina remain unknown. The segmental location of spasm indicates local hyperreactivity, but a diffuse increased coronary vasoconstriction, suggesting a substrate which could facilitate spasmogenic modifications, has been reported in many patients.1 The membrane sodium–hydrogen (Na+–H+) exchanger (NHE) is a major regulator of intracellular pH (pHi).2 An increased activity of the NHE isoform 1 (NHE-1) in smooth muscle cells has been suggested to favour vasoconstriction by causing intracellular alkalinisation and calcium overload.3 Furthermore, potential triggers of spasm (catecholamines, endothelin-1) have been shown to increase NHE-1 activity.4 In this study we investigated NHE-1 activity in platelets of patients with variant angina. The study group included 17 patients (13 men, 58 (9) years) with variant angina (angina attacks at rest, associated with transient ST segment elevation). Patients with hypertension and diabetes were excluded. The control group included 17 healthy subjects (13 men, 55 (6) years) without any history of chest pain, and with normal physical examination, ECG, and laboratory tests. ### Study protocol Because of ethical reasons, calcium antagonist drugs could not be withdrawn in patients, who, however, were invited not to take these drugs on the day of the study. Other drugs were withdrawn for more than one week before the study. A blood sample of 50 ml was drawn from an antecubital vein. To …

Myocarditis as a Cause of Alternating Left Bundle Branch Block

In the case report entitled “Loss of left bundle branch block following biventricular pacing therapy for heart failure: evidence for electrical remodeling” [1], Dizon et al. describe a case of a woman with NYHA class III heart failure and chronic left bundle branch block (LBBB) who had experienced an improvement in cardiac symptoms after a biventricular pacemaker implant. During the follow-up period a dislodgement of the left ventricular lead was detected, and the ECG showed disappearance of LBBB during intrinsic rhythm. The device therefore was turned to VVI mode at 40 bpm. The patient did well for two months, but then reported a worsening in heart failure symptoms. The ECG revealed recurrence of LBBB. The left ventricle lead was repositioned and the symptoms improved again. Dizon et al. [1] propose a beneficial effect of biventricular pacing on electrical remodeling as possible explanation for the loss of chronic LBBB. However, the mechanisms underlying the improvement and subsequent worsening of heart failure, the disappearance and subsequent recurrence of LBBB may be also independent from the beneficial effects of biventricular pacing. Myocarditis is another mechanism that could explain the clinical and electrocardiographic events. Most often seen as an acute entity, myocarditis may have a chronic evolution with phases of transient recurrences and improvements. Several previous papers have described the presence of a broad spectrum of conduction disturbances during infectious and non infectious myocarditis. Complete or advanced AV block was observed in 4% to 73% of patients with viral or idiopathic myocarditis [2–6], with complete or incomplete recovery in up to 80% of cases [6] and no correlation with the severity of left ventricular dysfunction at hospital admission [3]. In a study by Morgera et al., right bundle branch block was present in 13% of patients with active myocarditis histologically diagnosed. LBBB was present in 18% and was strongly correlated with the most severe involvement of left ventricular systolic function and poor prognosis [3]. These disturbances may disappear after resolution of myocarditis, with a variable time course [6,7]. Inflammatory edema and its spontaneous or drug-induced resolution seem to be the most probable mechanism to explain reversability of these conduction disturbances. A case of our own illustrates these points, with a clinical history much like the patient described by Dizon et al. [1]. The patient was admitted to our Cardiology Department with a history of heart failure first diagnosed one year before, in NYHA class III despite optimal medical therapy, presented with complete LBBB. The echocardiogram revealed left ventricular dilation and systolic dysfunction (EF 25%). He underwent biventricular pacing implant. At three months follow-up there was improvement of symptoms (from NYHA III to NYHA I), left ventricular dimensions and systolic function (EF from 25% to 45%), and disappearance of LBBB. The device was reprogrammed to VVI mode at rate of 40 bpm. Three months later the patient came back again to our attention for symptomatic congestive heart failure; the ECG showed a reappearance of complete LBBB and the echocardiogram demonstrated a severe left ventricular dysfunction and reappearance of dilation. An endomyocardial biopsy was performed revealing the

Altered electroanatomic patterns of right ventricle in myotonic dystrophy type 1 patients

Background: Prolongation of the atrial fibrillation cycle length (AFCL) and termination of AF during ablation have been reported. We investigate the significance of regions of maximal dominant frequency (DF) identified by spectral analysis, determining the effect of ablation at these sites located within the pulmonary veins (PV) on the fibrillatory process. Methods: Thirty-two patients undergoing AF ablation during ongoing arrhythmia were studied. Electroanatomic mapping was performed, acquiring 126 13 points/pt throughout both atria and coronary sinus (CS). At each point, 5s electrograms were obtained to determine the highest amplitude frequency on spectral analysis and construct 3D DF maps. Ablation was performed with the operator blinded to the DF maps. The effect of ablation at PVs with or without high-frequency DF sites (maximal frequencies surrounded by a decreasing frequency gradient 20%) was evaluated by determining the change in AFCL within the CS before and after isolation of each PV, and the termination of AF. Results: PV ablation was associated with an increase in AFCL (174 27 to 184 35ms; p 0.0001). While ablation at a PV harboring a DF site resulted in AFCL prolongation (180 30 to 198 40ms; p 0.0001), ablation at a PV without a DF site did not change the AFCL (169 22 to 170 22ms; p 0.4). Ablation at PVs harboring a DF site resulted in an increase in AFCL ( 5ms) within the CS in 89% with the mean increase in AFCL of 18 21ms (range 0-118ms) compared to 0.9 3.9ms (range -10 to 7ms; p 0.0001) after ablation at PVs without a DF site. The increase in AFCL with PV ablation demonstrated a strong concordance with ablation at a DF site (kappa-coefficient of 0.77). PV ablation resulted in AF termination in 14 pts; 11 at a DF site. In the remaining 3, 2 had frequent cessation of arrhythmia during mapping. Conclusion: High frequency PV activity identified by spectral analysis has an important role in maintaining AF. Ablation at these sites resulted in slowing of the fibrillatory process and termination of paroxysmal AF.