Faculty Bibliography

Blood potassium concentration [K+] has a strong influence on ECG and particularly on T-wave morphology. We previously developed a method to quantify [K+] from ECG analysis. The aims of the study were i) to test this method quantifying [K+] on a larger group of hemodialysis (HD) patients ii) to give a mechanical interpretation of the link between [K+] and ECG by testing the estimator on congenital LQT2 patients. The ECG-based potassium estimator (K-ECG), based on the ratio between the T-wave descending slope and the T-wave amplitude (T-S/A) was tested on 69 HD sessions (23 patients, 3 sessions each) and on 12 LQT2 patients. ECG recordings were acquired and [K+] values were measured from blood samples (K-LAB). The agreement between K-ECG and K-LAB was satisfactory in the HD patients (absolute error: 0.43 +/- 0.28mM). The systematic error was very small (0.05mM) while the standard deviation was 0.5mM. As expected, in LQT2 patients our method significantly underestimated [K+] (error: 1.15 +/- 0.68mM), thus pointing to the I-Kr dependence on extracellular potassium in determining the link between [K+] and T-wave morphology. This method could be effectively applied to monitor patients at risk for hyper- and hypokalemia.

AIMS: The European cardiac resynchronization therapy (CRT) survey is a joint initiative taken by the Heart Failure Association and the European Heart Rhythm Association of the European Society of Cardiology with the primary objective of describing current European practice associated with CRT implantations. The results demonstrated that a substantial number of implantations took place in patients without conventional guideline indications. We investigated whether the volume of implants per centre was a determinant of the propensity to use devices for 'off-label' indications. METHODS AND RESULTS: One hundred and forty-one centres from 13 European countries contributed data from consecutive patients successfully implanted with a CRT-P or CRT-D device between November 2008 and June 2009. Centres were categorized into low volume (LVol; </= 120 implantations/year) and high volume (HVol; >120 implantations/year) based on median implantable cardioverter-defibrilator implantation the previous year. No differences were noted with regard to sex, age, or peri-procedural and device-related complications. High-volume centres implanted CRT devices in significantly more patients with mild symptoms and a narrow QRS width. The procedure and fluoroscopy times were substantially longer at LVol centres and devices were more frequently implanted by surgeons and interventional cardiologists. Patients stayed longer in hospital in LVol centres with a median of 4 (2-9) vs. 2 (2-6) days. CONCLUSIONS: High-volume centres explore newer indications in their CRT practice and implant devices more frequently in patients with mild symptoms and narrow QRS durations. Electrophysiologists dominate implantation practice at HVol centres and duration of hospitalization is substantially shorter at these centres

Since the discovery of the genetic bases of the long QT syndrome, several new genetically mediated arrhythmias have been described, defining a new group of syndromes, called inherited arrhythmogenic diseases. This allowed clarifying the substrate of several cases of juvenile sudden death, previously defined as 'idiopathic ventricular fibrillation'. Studies derived from this field also contributed to advance the field of electrophysiology, elucidating some of the mechanisms that regulate the cardiac electrical properties of the heart. Recently, new genes and new proteins have been called into play, expanding the knowledge on the complexity of the regulatory processes modulating the cardiac action potential. Moreover, the collaboration between clinicians and basic scientists opened new approaches in the management of patients affected by genetic arrhythmias. This body of knowledge has then moved into the realization that genetic variations may also influence the predisposition to acquired cardiac diseases. The new exciting challenges that investigators are now facing are connected to the possibility of expanding the field towards the use of these information to shape a newer vision in the management and cure of patients

AIMS: Cardiac resynchronization therapy (CRT) is an effective treatment for a subset of patients with chronic heart failure. Data on the benefit of CRT in heart failure patients with previous right ventricular pacemakers or standard defibrillators are sparse. METHODS AND RESULTS: The European (HFA, Heart Failure Association/EHRA, European Heart Rhythm Association) CRT Survey enrolled patients from 141 centres in 13 countries in Europe collecting baseline demographic, echocardiographic, clinical, and implant data, with follow-up at approximately 1 year. The present analysis reports implantation data and 1 year outcomes regarding New York Heart Association (NYHA) class, global patient assessment, hospitalizations, complications, and mortality in patients undergoing de novo CRT implantations compared with those receiving an upgrade of a previously implanted device (pacemaker or implantable cardioverter-defibrillators). This analysis includes 2367 CRT implant procedures of which 692 (28%) were upgrades to CRT. Distribution of NYHA functional class and left ventricular function were similar between the groups. Procedural duration was also similar, although fluoroscopy time was shorter in the 'upgrades'. There was no difference in the frequency of peri-procedural complications. There were similar improvements in NYHA functional class and similar reduction in QRS duration, but more patients reported unchanged global assessment status in the upgraded group. Total and cause-specific mortality at 1 year was low and the same in both groups. CONCLUSIONS: More than one quarter of all CRT procedures are upgrades from existing systems, although this group has not been subject to randomized clinical trials. Our data suggest that there are no significant differences in clinical outcomes or complication rates between upgrades and de novo procedures. Clinical study no NCT 01185392

Rationale: Flecainide prevents arrhythmias in catecholaminergic polymorphic ventricular tachycardia, but the antiarrhythmic mechanism remains unresolved. It is possible for flecainide to directly affect the cardiac ryanodine receptor (RyR2); however, an extracellular site of action is suggested because of the hydrophilic nature of flecainide. Objective: To investigate the mechanism for the antiarrhythmic action of flecainide in a RyR2(R4496C+/-) knock-in mouse model of catecholaminergic polymorphic ventricular tachycardia. Methods and Results: Flecainide prevented catecholamine-induced sustained ventricular tachycardia in RyR2(R4496C+/-) mice. Cellular studies were performed with isolated RyR2(R4496C+/-) myocytes. Isoproterenol caused the appearance of spontaneous Ca(2+) transients, which were unaffected by flecainide (6 mumol/L). Flecainide did not affect Ca(2+) transient amplitude, decay, or sarcoplasmic reticulum Ca(2+) content. Moreover, it did not affect the frequency of spontaneous Ca(2+) sparks in permeabilized myocytes. In contrast, flecainide effectively prevented triggered activity induced by isoproterenol. The threshold for action potential induction was increased significantly (P<0.01), which suggests a primary extracellular antiarrhythmic effect mediated by Na(+) channel blockade. Conclusions: Flecainide prevents catecholaminergic polymorphic ventricular tachycardia in RyR2(R4496C+/-) mice; however, at variance with previous reports, we observed minimal effects on intracellular Ca(2+) homeostasis. Our data suggest that the antiarrhythmic activity of the drug is caused by reduction of Na(+) channel availability and by an increase in the threshold for triggered activity