Kostas Gatzoulis

Genotype-phenotype assessment in autosomal recessive arrhythmogenic right ventricular cardiomyopathy (Naxos disease) caused by a deletion in plakoglobin.

OBJECTIVES The purpose of this study was to examine the genotype-phenotype relation with respect to penetrance, age and severity of expression, disease progression and prognosis in a recessively inherited arrhythmogenic right ventricular cardiomyopathy (ARVC). BACKGROUND Naxos disease is a recessively inherited ARVC caused by a mutation in the gene encoding plakoglobin (cell adhesion protein) in which the cardiac phenotype is associated with palmoplantar keratoderma and woolly hair. METHODS Twelve families with Naxos disease underwent cardiac and molecular genetic investigation. Serial cardiac assessment with annual resting 12-lead and 24-h ambulatory electrocardiogram (ECG) and two-dimensional echocardiography was performed during 1 to 16 years, median 7 +/- 6 years in all 78 surviving members. RESULTS Twenty-eight surviving members were homozygous and 40 were heterozygous for the mutation. All adults who were homozygous (n = 26) fulfilled the diagnostic criteria for ARVC, the youngest by the age of 13 years. In eight who were heterozygous, minor ECG or echocardiographic abnormalities were observed. Of the 26 subjects who were affected homozygotes, 92% showed ECG abnormalities, 92% ventricular arrhythmias, 100% right ventricular structural alterations and 27% left ventricular involvement. During follow-up (10 +/- 6 years), 16 (62%) developed structural progression, 12 (46%) arrhythmic events and 7 (27%) heart failure. The annual disease-related and sudden death mortality was 3% and 2.3%, respectively. CONCLUSIONS Autosomal recessive ARVC caused by a mutation in plakoglobin was 100% penetrant by adolescence. Affected subjects who were homozygous experienced progressive disease with adverse prognosis. A minority of subjects who were heterozygous showed minor ECG/echocardiographic changes, but clinically significant disease did not develop.

Implantable defibrillator therapy in Naxos disease.

Naxos disease is a unique form of right ventricular cardiomyopathy with a high prevalence of malignant ventricular arrhythmias, including sudden cardiac death. As a hereditary systemic disease confined to a small island, it has been closely studied over the last 15 years. The implantation of an automatic defibrillator provides an alternative form of antiarrhythmic management to improve life expectancy in these high risk cardiac patients. We present the first two Naxos disease patients with malignant ventricular arrhythmias who had defibrillator implantation.

Polymorphic Ventricular Tachycardia Induced During Tilt Table Testing in a Patient with Syncope and Probable Dysfunction of the Sinus Node

We present a case of life‐threatening arrhythmia occurring during tilt table testing in a 44‐year‐old man with syncope. Polymorphic ventricular tachycardia occurred while the patient was tilted up under the intravenous infusion of isoproterenol (2 μg/min). No ischemia, QTc prolongation, or electrolyte abnormality preceded this event. The arrhythmia was not induced by programmed ventricular stimulation or exercise testing. Based on electrophysiological and clinical data, the diagnosis of sick sinus syndrome was entertained.

Inflammation in lone atrial fibrillation: New insights by coronary sinus thermography

BACKGROUND In the clinical setting there are conflicting results regarding the role of inflammatory activation in atrial fibrillation (AF). Coronary sinus (CS) thermography assesses myocardial heat production and is correlated with inflammatory states. We investigated in patients with AF whether 1) there is increased CS blood temperature and 2) the correlation of heat production with systemic inflammation. METHODS We included patients with AF and subjects with sinus rhythm. C-reactive protein (CRP) levels were measured in all patients. CS and right atrium (RA) blood temperature measurements were performed by a dedicated 7F thermography catheter. DeltaT was calculated by subtracting RA from CS blood temperature. RESULTS We included 47 patients with AF and 23 subjects with sinus rhythm. We stratified patients with AF into two groups: normotensive (AFN) and hypertensive (AFH). DeltaT was lower in the RA compared with the CS in AFH (37.27+/-0.52 degrees C vs 37.47+/-0.54 degrees C, p<0.01), in AFN (37.13+/-0.53 degrees C vs 37.34+/-0.54 degrees C, p<0.01), and in controls (37.41+/-0.69 degrees C vs 37.55+/-0.68 degrees C, p<0.01). DeltaTau was greater in AFH, and AFN compared to controls (0.20+/-0.07 degrees C, 0.20+/-0.08 degrees C, vs 0.14+/-0.06 degrees C, p<0.01). DeltaT was similar between AFH and AFN (p=0.95). CRP was higher in AFH and AFN compared to controls (1.72+/-0.85 mg/Dl, 1.69+/-0.94 mg/dL, 0.98+/-0.71 mg/dL, p<0.01). CRP was similar between AFH and AFN (p=0.87). A correlation between CRP with DeltaT was observed in AFH and AFN (R=0.58, p<0.01, R=0.44, p=0.02). CONCLUSIONS Patients with AF have increased myocardial heat production, which is correlated to the systemic inflammation. CS blood temperature measurement may provide significant information for the pathogenesis of AF.

Neurocardiogenic Syncope Aetiology and Management

Neurocardiogenic syncope is the most common cause of syncope presenting in the outpatient setting. It is usually encountered among individuals without an underlying heart disease, but not uncommonly participates in the syncope mechanism of patients with an obstructive or an arrhythmic cardiac cause for syncope as well. The vasovagal event is caused by a transient profound hypotensive reaction most commonly associated with inappropriate bradycardia resulting from activation of a complex autonomic reflex. The pathophysiology of neurocardiogenic syncope has been elucidated by tilt table testing, a noninvasive and well-tolerated method for reproducing the event in susceptible individuals.Although the majority of people with vasovagal fainting need no specific treatment, treatment is required for those presenting with problematic features such as frequent events accompanied by trauma or accidents, and occasionally by a severe cardioinhibitory pattern response. A number of different drugs have been proposed to favourably act on different aspects of the neurocardiogenic reflex but only a few randomised, placebo-controlled, drug-specific trials are currently available. Alternatively, cardiac pacing has also been introduced for patients who have symptoms that are drug-refractory or for those with a severe cardioinhibitory hypotensive response.The selection of the appropriate treatment plan should be individualised after consideration of patient history, clinical characteristics and preference, results of the baseline tilting study, and the existing evidence from the few randomised, controlled studies performed so far.

Mild left ventricular hypertrophy in essential hypertension: is it really arrhythmogenic?

Left ventricular hypertrophy (LVH) has been associated with an increased incidence of ventricular arrhythmias and sudden cardiac death in hypertensive patients. However, it is not known whether this relationship exists in early asymptomatic hypertensives with mild LVH. We prospectively examined 100 consecutive patients with essential hypertension, 35 without and 65 with mild LVH on echocardiography. All underwent a detailed noninvasive arrhythmia work-up and were subsequently followed-up for 3 +/- 1 years in an ambulatory hypertension clinic. None of the 12-lead electrocardiographic parameters examined differed between the two hypertensive groups. A similarly low incidence of simple forms of ventricular ectopy was present in both groups, whereas complex forms of ventricular ectopy were extremely rare in either group. The signal-averaged electrocardiographic parameters examined were also not significantly affected by the presence of mild LVH. Arrhythmia-related symptoms or malignant ventricular arrhythmia events were not observed in either group of patients during follow-up with antihypertensive treatment. The latter resulted in LVH regression in the 65 patients with mild LVH at baseline. It appears that mild LVH among ambulatory hypertensive patients does not carry an additive arrhythmogenic risk and can be successfully reversed with the appropriate antihypertensive therapy, with no need of additional antiarrhythmic management.

Right Posterior Atrioventricular Ring: A Location For Different Types of Atrioventricular Accessory Connections

We present an unusual case of a 28-year-old female patient with recurrent episodes of tachycardias due to participation of two accessory connections located in the posterior tricuspid annulus. Both connections were of the atrioventricular type, the one with non decremental fast conducting properties at the right posteroseptal area, the other with node-like properties at the posterolateral tricuspid ring. Both pathways were successfully ablated transvenously with radiofrequency energy application at the same session. Implications about a common embryological origin of the two pathways as well as review of the literature for similar cases are presented.

Tilt‐Table Testing in Syncopal Patients with Sick Sinus Syndrome: A Guide to Pathophysiology and Management?

A possible role of a neurally mediated component in the syncope mechanism of patients with sick sinus syndrome has not been adequately evaluated.

Spontaneous twisting of an implanted pacemaker electrode in three cases.

We present three cases of an unusual pacing lead aberration occurring at different times after implantation. In the first patient, the electrode was twisted close to the pacemaker, and dislodgment occurred on the 40th postoperative day. In the second case, there was only proximal twisting of the electrode. In the third case the electrode was twisted in two places: proximal to the pacemaker, and distal, within the right atrium. The complication was managed successfully by reimplanting the same electrode after stiffening the lead near the generator with a portion of the stylet.