Matteo Iori

Benefit of Pacemaker Therapy in Patients With Presumed Neurally Mediated Syncope and Documented Asystole Is Greater When Tilt Test Is Negative An Analysis From the Third International Study on Syncope of Uncertain Etiology (ISSUE-3)

Background—In the Third International Study on Syncope of Uncertain Etiology (ISSUE-3), cardiac pacing was effective in reducing recurrence of syncope in patients with presumed neurally mediated syncope (NMS) and documented asystole but syncope still recurred in 25% of them at 2 years. We have investigated the role of tilt testing (TT) in predicting recurrences. Methods and Results—In 136 patients enrolled in the ISSUE-3, TT was positive in 76 and negative in 60. An asystolic response predicted a similar asystolic form during implantable loop recorder monitoring, with a positive predictive value of 86%. The corresponding values were 48% in patients with non–asystolic TT and 58% in patients with negative TT (P=0.001 versus asystolic TT). Fifty-two patients (26 TT+ and 26 TT–) with asystolic neurally mediated syncope received a pacemaker. Syncope recurred in 8 TT+ and in 1 TT– patients. At 21 months, the estimated product-limit syncope recurrence rates were 55% and 5%, respectively (P=0.004). The TT+ recurrence rate was similar to that seen in 45 untreated patients (control group), which was 64% (P=0.75). The recurrence rate was similar between 14 patients with asystolic and 12 with non–asystolic responses during TT (P=0.53). Conclusions—Cardiac pacing was effective in neurally mediated syncope patients with documented asystolic episodes in whom TT was negative; conversely, there was insufficient evidence of efficacy from this data set in patients with a positive TT even when spontaneous asystole was documented. Present observations are unexpected and need to be confirmed by other studies. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT01463358.

Intravenous administration of flecainide or propafenone in patients with recent-onset atrial fibrillation does not predict adverse effects during ‘pill-in-the-pocket’ treatment

Background Pill-in-the-pocket treatment should be prescribed only if the administration of a loading oral dose of flecainide or propafenone has been proved safe in hospital, since major adverse effects have been reported in 5% of patients during in-hospital treatment. However, in emergency rooms, the oral administration of these drugs for the conversion of atrial fibrillation (AF) is very rarely used because it is time consuming. Objective To investigate whether tolerance to intravenous administration of flecainide or propafenone might predict the safety of pill-in-the-pocket treatment—the out-of-hospital self-administration of these drugs after the onset of palpitations—in patients with AF of recent onset. Methods One hundred and twenty-two patients with AF of recent onset who were successfully treated (conversion of AF within 2 h without major adverse effects) in hospital with intravenous flecainide or propafenone were discharged on pill-in-the-pocket treatment. Results During a mean follow-up of 11±4 months, 79 patients self-treated 213 arrhythmic episodes; treatment was successful in 201 episodes (94%). Major adverse events occurred in five patients (6%) and in four (5%) of these during the first oral treatment (one syncope, two presyncope, one sinus arrest). No patient reported symptoms attributable to bradyarrhythmia or hypotension during the self-treatment of arrhythmic recurrences when the first oral treatment was not accompanied by any major adverse effects. The study was prematurely terminated because of the high incidence of major adverse effects during the first out-of-hospital treatment. Conclusion The patients tolerance of intravenous administration of flecainide or propafenone does not seem to predict adverse effects during out-of-hospital self-administration of these drugs.

Device Longevity in a Contemporary Cohort of ICD/CRT-D Patients Undergoing Device Replacement.

The longevity of defibrillators (ICD) is extremely important from both a clinical and economic perspective. We studied the reasons for device replacement, the longevity of removed ICD, and the existence of possible factors associated with shorter service life.

Adenosine and Clinical Forms of Neurally-Mediated Syncope

Central or peripheral baroreceptor reflex abnormalities, alterations in neurohumoral mechanisms, or both, are thought to play a role in causing neurally-mediated syncope. Because adenosine and its receptors are involved in some forms of syncope [(1–3)][1], we evaluated the purinergic profile of 4

Efficacy of theophylline in patients affected by low adenosine syncope.

Background: Adenosine, an ATP derivative, may be implicated in some kinds of unexplained syncope. In patients with normal heart, normal ECG and recurrent sudden-onset syncope without prodromes have been shown to present with lowplasmatic adenosine levels and a high susceptibility to exogenous adenosine.The term “low-adenosine syncope” has been launched to describe this distinct clinical entity. Objectives: We decided to investigate whether chronic treatment of these patients with theophylline, a non-selective adenosine receptor antagonist, results in clinical benefit. Methods. We report on the prolonged clinical observation of 6 “low-adenosine” syncope patients (mean age 50±20 years, 4 females) treated with oral theophylline within the therapeutic range of 12-18 μg/ml. We were able to make an intrapatient comparison between a period with and a period without theophylline therapy. Results: In five patients, symptoms disappeared and the number of prolonged asystolic pauses detected by implantable loop recorder (ILR) fell impressively from a median of 1.11 per month (interquartile range 0.4 -1.8)during 13 months of no-treatment (range 2-36) to 0 per month(0-0.7) during 20 months of theophylline treatment (range 6-120). The 6th patient, was unresponsive to theophylline therapy, and a different mechanism of syncope was hypothesized. Conclusion: In this small series of highlyselected patients affected by syncope with low circulating adenosine levels, theophylline proved to be an effective therapy in most patients. The logical inference is that the adenosine pathway has a causal role in the mechanism of syncope in such patients.

Long-term clinical outcome of patients who failed catheter ablation of atrial fibrillation.

AIMS Left atrial ablation fails to prevent symptomatic recurrences of atrial fibrillation (AF) in 20-30% of patients up to 3 years of follow-up despite multiple procedures. Data are lacking on the long-term clinical outcome of those patients for whom the decision was taken to renounce performing further ablation procedures. METHODS AND RESULTS In this multicentre study, 218 (34%) of 631 consecutive patients, who had undergone AF catheter ablation in the years 2001-11 for drug-refractory symptomatic AF, had symptomatic AF recurrences after 1.5 ± 0.6 procedures. Their long-term clinical outcome was assessed in March 2012 (minimum follow-up 1 year). At a mean of 5.1 ± 2.6 years since their last ablation, 82 (38%) patients improved, 103 (47%) remained unchanged and 33 (15%) worsened, but only 17 (8%) had such a severe impairment of their quality of life as to require atrioventricular junction ablation and pacing (#13) or cardiac surgery (#4); 22 (10%) patients had had adverse clinical events (death in five, heart failure in five, stroke and transient ischaemic cerebral attack in four, severe haemorrhage in four, pacemaker or implantable cardioverter-defibrillator implantation in seven) and 98 (45%) patients had developed permanent AF. Compared with patients without permanent AF, fewer patients with permanent AF improved (3% vs. 66%, P = 0.001) and more got worse (28% vs. 5%, P = 0.001). At multivariable logistic regression, single ablation procedure, left atrial diameter, persistent AF and time from the last ablation were independent predictors of permanent AF. CONCLUSION More than 5 years after a failed AF ablation, a small minority of patients had such an impaired quality of life as to require non-pharmacological interventions. Almost half developed permanent AF, which significantly impaired quality of life. Permanent AF was more common in patients who had left atrial enlargement, history of persistent AF, longer follow-up, and had performed a single ablation procedure, thus hypothesizing that reablation could reduce the chronicization of arrhythmia. A low risk of stroke was observed in the long-term follow-up.

Sudden death in a patient with idiopathic right ventricular outflow tract arrhythmia.

Idiopathic ventricular tachycardia originating from the right ventricular outflow tract (RVOT) and idiopathic RVOT extrasystoles are generally considered benign arrhythmias. We describe the case of a patient with typical RVOT arrhythmias without any symptoms for many years, who died suddenly the day before a planned electrophysiological study. The only disquieting signs in her clinical history were a relatively short coupling interval of premature ventricular contractions in some ECG recordings and an isolated run of polymorphic nonsustained ventricular tachycardia induced by an RVOT extrasystole during previous ECG monitoring.

Radiofrequency catheter ablation of atrioventricular nodal re-entry tachycardia: selective approach to the slow pathway via the cephalic veins

Inferior venous access to the right heart is not possible in some patients due to vena caval obstruction. Here we describe a case of a patient with atrioventricular nodal re-entry tachycardia where radiofrequency ablation from the inferior vena cava was impossible because of the presence of important stenosis of the distal part of the vein. Catheter ablation of the slow pathway could be performed successfully using a superior approach via the cephalic veins.

P‐Wave Amplitude and PR Changes in Patients With Inappropriate Sinus Tachycardia: Findings Supportive of a Central Mechanism

Background The mechanism of inappropriate sinus tachycardia (IST) remains incompletely understood. Methods and Results We prospectively compared 3 patient groups: 11 patients with IST (IST Group), 9 control patients administered isoproterenol (Isuprel Group), and 15 patients with cristae terminalis atrial tachycardia (AT Group). P‐wave amplitude in lead II and PR interval were measured at a lower and higher heart rate (HR1 and HR2, respectively). P‐wave amplitude increased significantly with the increase in HR in the IST Group (0.16±0.07 mV at HR1=97±12 beats per minute versus 0.21±0.08 mV at HR2=135±21 beats per minute, P=0.001). The average increase in P‐wave amplitude in the IST Group was similar to the Isuprel Group (P=0.26). PR interval significantly shortened with the increases in HR in the IST Group (146±15 ms at HR1 versus 128±16 ms at HR2, P<0.001). A similar decrease in the PR interval was noted in the Isuprel Group (P=0.6). In contrast, patients in the atrial tachycardia Group experienced PR lengthening during atrial tachycardia when compared with baseline normal sinus rhythm (153±25 ms at HR1=78±17 beats per minute versus 179±29 ms at HR2=140±28 beats per minute, P<0.01). Conclusions We have shown that HR increases in patients with IST were associated with an increase in P‐wave amplitude in lead II and PR shortening similar to what is seen in healthy controls following isoproterenol infusion. The increase in P‐wave amplitude and absence of PR lengthening in IST support an extrinsic mechanism consistent with a state of sympatho‐excitation with cephalic shift in sinus node activation and enhanced atrioventricular nodal conduction.

A randomized controlled trial of atrioventricular junction ablation and cardiac resynchronization therapy in patients with permanent atrial fibrillation and narrow QRS

Aims We tested the hypothesis that atrioventricular (AV) junction ablation in conjunction biventricular pacing [cardiac resynchronization (CRT)] pacing is superior to pharmacological rate-control therapy in reducing heart failure (HF) and hospitalization in patients with permanent atrial fibrillation (AF) and narrow QRS. Methods and results We randomly assigned 102 patients (mean age 72 ± 10 years) with severely symptomatic permanent AF (>6 months), narrow QRS (≤110 ms), and at least one hospitalization for HF in the previous year to AV junction ablation and CRT (plus defibrillator according to guidelines) or to pharmacological rate-control therapy (plus defibrillator according to guidelines). After a median follow-up of 16 months, the primary composite outcome of death due to HF, or hospitalization due to HF, or worsening HF had occurred in 10 patients (20%) in the Ablation+CRT arm and in 20 patients (38%) in the Drug arm [hazard ratio (HR) 0.38; 95% confidence interval (CI) 0.18-0.81; P = 0.013]. Significantly fewer patients in the Ablation+CRT arm died from any cause or underwent hospitalization for HF [6 (12%) vs. 17 (33%); HR 0.28; 95% CI 0.11-0.72; P = 0.008], or were hospitalized for HF [5 (10%) vs. 13 (25%); HR 0.30; 95% CI 0.11-0.78; P = 0.024]. In comparison with the Drug arm, Ablation+CRT patients showed a 36% decrease in the specific symptoms and physical limitations of AF at 1 year follow-up (P = 0.004). Conclusion Ablation+CRT was superior to pharmacological therapy in reducing HF and hospitalization and improving quality of life in elderly patients with permanent AF and narrow QRS. ClinicalTrials.gov Identifier NCT02137187 (May 2018, date last accessed).