Elena Richiardi

Short QT Syndrome: a familial cause of sudden death.

Background—A prolonged QT interval is associated with a risk for life-threatening events. However, little is known about prognostic implications of the reverse—a short QT interval. Several members of 2 different families were referred for syncope, palpitations, and resuscitated cardiac arrest in the presence of a positive family history for sudden cardiac death. Autopsy did not reveal any structural heart disease. All patients had a constantly and uniformly short QT interval at ECG. Methods and Results—Six patients from both families were submitted to extensive noninvasive and invasive work-up, including serial resting ECGs, echocardiogram, cardiac MRI, exercise testing, Holter ECG, and signal-averaged ECG. Four of 6 patients underwent electrophysiological evaluation including programmed ventricular stimulation. In all subjects, a structural heart disease was excluded. At baseline ECG, all patients exhibited a QT interval ≤280 ms (QTc ≤300 ms). During electrophysiological study, short atrial and ventricular refractory periods were documented in all and increased ventricular vulnerability to fibrillation in 3 of 4 patients. Conclusions—The short QT syndrome is characterized by familial sudden death, short refractory periods, and inducible ventricular fibrillation. It is important to recognize this ECG pattern because it is related to a high risk of sudden death in young, otherwise healthy subjects.

Long-term follow-up of right ventricular monomorphic extrasystoles.

OBJECTIVES The purpose of this study was to verify in a long-term follow-up whether frequent monomorphic right ventricle extrasystoles may progress to arrhythmogenic right ventricular dysplasia (ARVD). BACKGROUND Frequent monomorphic right ventricle extrasystoles are generally considered benign. However, in patients with this pattern, cardiac magnetic resonance (MR) has recently shown anatomical and functional abnormalities of the right ventricle. METHODS Sixty-one patients who had been classified by noninvasive examinations as having frequent idiopathic right ventricle ectopy were contacted after 15 +/- 2 years (12 to 20) and submitted to clinical examination, electrocardiogram (ECG), Holter monitoring, stress test, signal averaged ECG, echocardiography and, in 11 patients, cardiac MR. The primary end point was to ascertain the presence of cases of sudden death or progression to ARVD. RESULTS At the end of the follow-up, 55 patients were alive; six died, none of sudden death; eight stated to be well but refused further examinations. The 47 patients examined had normal ECG; in 24 patients (51%), extrasystoles were no longer present at Holter monitoring; late potentials were present in up to 15% of the patients; the right ventricle was normal at echocardiography. In 8 of 11 patients (73%), cardiac MR showed focal fatty replacement and other abnormalities of the right ventricle. CONCLUSIONS In this long-term follow-up study, no patient died of sudden death nor developed ARVD; two-thirds of the patients were asymptomatic, and, in half of the patients, ectopy had disappeared. Focal fatty replacement in the right ventricle was present in most.

Short QT Syndrome

Short QT syndrome is a new genetic disorder associated with familial atrial fibrillation and/or sudden death or syncope. To date, different mutations in genes encoding for cardiac ion channels (KCNH2, KCNQ1, and KCNJ2) have been identified to cause the short QT syndrome. The mutations lead to a gain of function of the affected current (IKr, IKs, and IK1). The phenotype is characterized by a shortened QT interval<335 ms after correction for heart rate at rates<80 beats/min. Furthermore, the QT interval poorly adapts to heart rate. Patients exhibit shortened atrial and ventricular effective refractory periods and, in the majority, inducibility of ventricular fibrillation. Death occurs already in newborns. Therapy of choice seems to be the implantable cardioverter defibrillator because of the high incidence of sudden death. Pharmacological treatment has been studied and it could be demonstrated, that some mutant currents may be insufficiently suppressed by drugs targeted to block the specific current such as, e.g., sotalol or ibutilide in patients with a mutation in the IKr-coding gene KCNH2 (HERG). Quinidine proved to be efficient in prolonging the QT interval and normalizing the effective refractory periods in some patients.

Arrhythmogenic right ventricular cardiomyopathy: ECG progression over time and correlation with long-term follow-up.

Aims Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited heart muscle disease primarily affecting the right ventricle and potentially causing sudden death in young people. Our aims are to analyse the progression over time of electrocardiographic (ECG) findings and to investigate their prognostic impact. Methods Sixty-eight patients (69% men; age 31 ± 19 years) with ARVC diagnosis were followed up for a mean of 17 ± 8 years. Follow-up included baseline ECG, 24-h Holter ECG, signal-averaged ECG, stress test, echocardiography, cardiac magnetic resonance and electrophysiologic study. Results During follow-up 12 (18%) patients died: three of sudden cardiac death (SCD), four of end-stage heart failure and five of noncardiac causes. Aborted SCD occurred in 7 (10%) patients, syncope in 31 (46%), sustained ventricular tachycardia in 43 (63%), heart failure in 18 (26%), atrial fibrillation in 16 (24%) and 3 (4%) patients underwent heart transplant. Twenty-four (35%) patients had implantable cardiac defibrillator (15 and 5 of them received both appropriate and inappropriate interventions, respectively and 7 experienced device-related complications). Of the ECG parameters registered at the enrolment, left anterior fascicular block (P = 0.001), QRS duration in lead 1 (P < 0.001), Epsilon wave (P < 0.001), T wave inversion in V4–V5–V6 (P = 0.012, P = 0.001 and P = 0.006) and low QRS voltages (P = 0.001) progressed over time. At multivariate analysis Epsilon wave (odds ratio 20.9, confidence interval 95% 1.8–239.8, P = 0.015) was the only predictor of the composite endpoint of SCD, heart failure-related death or heart transplant. Conclusion Apart from playing a pivotal role in ARVC diagnosis, a simple ECG feature such as Epsilon wave is a marker of poor prognosis.

Short- and long-term effects of propafenone in ventricular arrhythmias

The effectiveness of short- (15 days) and long- (12 months) term propafenone treatment was assessed in 53 patients presenting with more than 30 premature ventricular complexes per hour as detected by 24-hour ambulatory Holter monitoring. Thirty-nine patients had no apparent concomitant heart disease while 14 had chronic coronary artery disease. The effects of propafenone were analysed by ambulatory Holter monitoring after 15 days and at 3, 6 and 12 months. The initial dose was 150 mg four times daily and was increased up to 300 mg four times daily when necessary. Favourable short-term effects were obtained in 39 patients (73.6%). After 12 months, 17 patients (32.1%) were still on propafenone treatment with good results. Treatment was discontinued on account of low compliance in 28.3%. This was because treatment was ineffective even at high doses in 15.2%, because of severe side effects in 13.2%, because of proarrhythmic effects in 5.6% and for other causes in 5.6%.

Phenotypic expression of ARVC: How 12 lead ECG can predict left or right ventricle involvement. A familiar case series and a review of literature

AIMS Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited heart-muscle disease primarily affecting the right ventricle (RV) and potentially causing sudden death in young people. The natural history of the disease is firstly characterized by a concealed form progressing over a biventricular involvement. Three different cases coming from the same family are presented together with a review of the literature. METHODS AND RESULTS Multi-parameter analysis including imaging and electrocardiographic analysis is presented since the first medical referral with follow-up ranging from 11 to 38years. Case 1 presented a typical RV involvement in agreement with the ECG pattern. Case 2 presented a prevalent left ventricular involvement leading from the beginning to a pattern of dilated cardiomyopathy in agreement with his ECG evolution over the years. On the other side, Case 3 came to observation with a typical RV involvement (similar to Case 1) but with ECG evolution of typical left ventricle involvement (similar to Case 2). The genetic analysis showed a mutation in desmoglein-2 (DSG2) gene: p. Arg49His. Comparison between size and localization of ventricular dyskinesia at cardiovascular imaging and the surface 12 lead electrocardiography are proposed. CONCLUSIONS ARVC may lead to an extreme phenotypic variability in clinical manifestations even within patients coming from the same family in which ARVC is caused by the same genetic mutation. ECG progression over time reflects disease evolution and in particular cases may anticipate wall motion abnormalities by years.

Physiology of AV Junction: What Have We Learnt from Radiofrequency Ablation?

The atrioventricular (AV) junction is a rather complex structure involved in the genesis of the atrioventricular junctional reentrant tachycardia (AVJRT), which is the most frequent supraventricular arrhythmia. The advent of radiofrequency (RF) catheter ablation, that has been developed in the recent years, has provided a new therapeutic tool for the radical cure of this arrhythmia. In the meantime the more precise and extensive mapping of the septal region has provided new insight in the physiology and anatomy of the AV junction. This has led to questioning of some previously accepted concepts on its electrophysiology, and rekindled the interest of anatomists and experimental and clinical electrophysiologists, particularly in relation to the mechanism of reentry in humans.