Combining home monitoring temporal trends from implanted defibrillators and baseline patient risk profile to predict heart failure hospitalizations: results from the SELENE HF study.

AIMS: We developed and validated an algorithm for prediction of heart failure (HF) hospitalizations using remote monitoring (RM) data transmitted by implanted defibrillators. METHODS AND RESULTS: The SELENE HF study enrolled 918 patients (median age 69 years, 81% men, median ejection fraction 30%) with cardiac resynchronization therapy (44%), dual-chamber (38%), or single-chamber defibrillators with atrial diagnostics (18%). To develop a predictive algorithm, temporal trends of diurnal and nocturnal heart rates, ventricular extrasystoles, atrial tachyarrhythmia burden, heart rate variability, physical activity, and thoracic impedance obtained by daily automatic RM were combined with a baseline risk-stratifier (Seattle HF Model) into one index. The primary endpoint was the first post-implant adjudicated HF hospitalization. After a median follow-up of 22.5 months since enrolment, patients were randomly allocated to the algorithm derivation group (n = 457; 31 endpoints) or algorithm validation group (n = 461; 29 endpoints). In the derivation group, the index showed a C-statistics of 0.89 [95% confidence interval (CI): 0.83-0.95] with 2.73 odds ratio (CI 1.98-3.78) for first HF hospitalization per unitary increase of index value (P < 0.001). In the validation group, sensitivity of predicting primary endpoint was 65.5% (CI 45.7-82.1%), median alerting time 42 days (interquartile range 21-89), and false (or unexplained) alert rate 0.69 (CI 0.64-0.74) [or 0.63 (CI 0.58-0.68)] per patient-year. Without the baseline risk-stratifier, the sensitivity remained 65.5% and the false/unexplained alert rates increased by ≈10% to 0.76/0.71 per patient-year. CONCLUSION: With the developed algorithm, two-thirds of first post-implant HF hospitalizations could be predicted timely with only 0.7 false alerts per patient-year.

Standardized algorithm for cardiac pacing in older patients affected by severe unpredictable reflex syncope: 3-year insights from the Syncope Unit Project 2 (SUP 2) study.

AIMS: The aim of this study was to determine the long-term effects and determinants of success of cardiac pacing in patients affected by reflex syncope enrolled in the Syncope Unit Project 2 (SUP 2) study. Initial results have validated the effectiveness of a standardized guideline-based algorithm which can be used in clinical practice in order to select suitable candidates for cardiac pacing. METHODS AND RESULTS: In this prospective, multicentre, observational study, patients aged >40 years, affected by severe unpredictable recurrent reflex syncope, underwent carotid sinus massage (CSM), followed by tilt testing (TT) if CSM was negative, followed by implantation of an implantable loop recorder (ILR) if TT was negative. Those who had an asystolic response to one of these tests received a dual-chamber pacemaker. Of 281 patients who met the inclusion criteria, 137 (49%) received a pacemaker and were followed up for a mean of 26 ± 11 months: syncope recurred in 25 (18%) of them. At 3 years, the actuarial syncope recurrence rate was 20% [95% confidence interval (CI) 12-30] and was significantly lower than in 142 patients who did not receive a pacemaker and were observed by means of an ILR [43% (95% CI 29-57), P = 0.01]. The 3-year recurrence rate was not different among 78 CSM+, 38 TT+, and 21 ILR+ patients, whereas it was lower in 20 patients with negative TT [5% (95% CI 0-15)] than in 61 patients with positive TT [24% (95% CI 10-38)]. CONCLUSION: The benefit of cardiac pacing is maintained at 3 years, irrespective of the index diagnostic test, and is maximum in patients with negative TT. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01509534.

Assessment of a standardized algorithm for cardiac pacing in older patients affected by severe unpredictable reflex syncopes.

AIMS: Opinions differ regarding the effectiveness of cardiac pacing in patients affected by reflex syncope. We assessed a standardized guideline-based algorithm in different forms of reflex syncope. METHODS AND RESULTS: In this prospective, multi-centre, observational study, patients aged >40 years, affected by severe unpredictable recurrent reflex syncopes, underwent carotid sinus massage (CSM), followed by tilt testing (TT) if CSM was negative, followed by implantation of an implantable loop recorder (ILR) if TT was negative. Those who had an asystolic response to one of these tests received a dual-chamber pacemaker. POPULATION: 253 patients, mean age 70 ± 12 years, median 4 (3-6) syncopes, 89% without or with short prodromes. Of these patients, 120 (47%) received a pacemaker and 106 were followed up for a mean of 13 ± 7 months: syncope recurred in 10 (9%). The recurrence rate was similar in 61 CSM+ (11%), 30 TT+ (7%), and 15 ILR+ (7%) patients. The actuarial total syncope recurrence rate was 9% (95% confidence interval (CI), 6-12) at 1 year and 15% (95% CI, 10-20) at 2 years and was significantly lower than that observed in the group of 124 patients with non-diagnostic tests who had received an ILR: i.e. 22% (95% CI, 18-26) at 1 year and 37% (95% CI, 30-43) at 2 years (P = 0.004). CONCLUSION: About half of older patients with severe recurrent syncopes without prodromes have an asystolic reflex for which cardiac pacing goes along with a low recurrence rate. The study supports the clinical utility of the algorithm for the selection of candidates to cardiac pacing in everyday clinical practice. CLINICAL TRIAL REGISTRATION: http://www.clinicaltrials.gov. Unique identifier: NCT01509534.

Cardiac pacing in patients with neurally mediated syncope and documented asystole: effectiveness analysis from the Third International Study on Syncope of Uncertain Etiology (ISSUE-3) Registry.

AIMS: The randomized, double-blind Third International Study on Syncope of Uncertain Etiology (ISSUE-3) showed that dual-chamber permanent pacing was effective in reducing the recurrence of syncope in patients ≥ 40 years with severe asystolic, probably neurally mediated syncope (NMS), documented by implantable loop recorder (ILR). Analysis in ISSUE-3 was performed according to the intention-to-treat principle. In the present study, we performed an on-treatment analysis, which included additionally those non-randomized patients followed up in the ISSUE registry to evaluate in a better manner the effectiveness of cardiac pacing therapy. METHODS AND RESULTS: Initially, 504 patients received an ILR, 162 (32%) patients had a diagnosis consistent with NMS within a mean observation period of 15 ± 11 months: 99 (19%) patients had documentation of syncope with ≥ 3 s asystole or ≥ 6 s asystole without syncope. Sixty patients affected by asystolic NMS received cardiac pacing therapy and 86 (33 asystolic and 53 non-asystolic NMS) were untreated; 16 patients were lost to follow-up. Paced and unpaced groups had similar clinical characteristics. During subsequent follow-up, syncope recurred in 10 paced (17%) and in 40 non-paced (46%) patients. At 21 months, the estimated product-limit syncope recurrence rates were 27% [95% confidence interval (CI) 15-47] and 54% (95% CI 43-67), respectively (P = 0.01). With cardiac pacing, the risk of recurrence was reduced by 57% (hazard ratio = 0.43, 95% CI = 0.2-0.8). Complications of pacemaker therapy were haemothorax at implantation in one patient and lead dislodgement that required correction in two patients. CONCLUSION: Permanent cardiac pacing is effective in reducing recurrence of syncope in patients ≥ 40 years with severe asystolic possible NMS with a few complications. The study shows that 61% of patients with a diagnosis of NMS made by ILR received a pacemaker but 5.1 ILRs had to be implanted to find one patient who finally had a pacemaker implanted.

Pacemaker therapy in patients with neurally mediated syncope and documented asystole: Third International Study on Syncope of Uncertain Etiology (ISSUE-3): a randomized trial.

BACKGROUND: The efficacy of cardiac pacing for prevention of syncopal recurrences in patients with neurally mediated syncope is controversial. We wanted to determine whether pacing therapy reduces syncopal recurrences in patients with severe asystolic neurally mediated syncope. METHODS AND RESULTS: Double-blind, randomized placebo-controlled study conducted in 29 centers in the Third International Study on Syncope of Uncertain Etiology (ISSUE-3) trial. Patients were ≥40 years, had experienced ≥3 syncopal episodes in the previous 2 years. Initially, 511 patients, received an implantable loop recorder; 89 of these had documentation of syncope with ≥3 s asystole or ≥6 s asystole without syncope within 12 ± 10 months and met criteria for pacemaker implantation; 77 of 89 patients were randomly assigned to dual-chamber pacing with rate drop response or to sensing only. The data were analyzed on intention-to-treat principle. There was syncope recurrence during follow-up in 27 patients, 19 of whom had been assigned to pacemaker OFF and 8 to pacemaker ON. The 2-year estimated syncope recurrence rate was 57% (95% CI, 40-74) with pacemaker OFF and 25% (95% CI, 13-45) with pacemaker ON (log rank: P=0.039 at the threshold of statistical significance of 0.04). The risk of recurrence was reduced by 57% (95% CI, 4-81). Five patients had procedural complications: lead dislodgment in 4 requiring correction and subclavian vein thrombosis in 1 patient. CONCLUSIONS: Dual-chamber permanent pacing is effective in reducing recurrence of syncope in patients ≥40 years with severe asystolic neurally mediated syncope. The observed 32% absolute and 57% relative reduction in syncope recurrence support this invasive treatment for the relatively benign neurally mediated syncope. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00359203.

Outpatient treatment of recent-onset atrial fibrillation with the "pill-in-the-pocket" approach.

BACKGROUND: In-hospital administration of flecainide and propafenone in a single oral loading dose has been shown to be effective and superior to placebo in terminating atrial fibrillation. We evaluated the feasibility and the safety of self-administered oral loading of flecainide and propafenone in terminating atrial fibrillation of recent onset outside the hospital. METHODS: We administered either flecainide or propafenone orally to restore sinus rhythm in 268 patients with mild heart disease or none who came to the emergency room with atrial fibrillation of recent onset that was hemodynamically well tolerated. Of these patients, 58 (22 percent) were excluded from the study because of treatment failure or side effects. Out-of-hospital self-administration of flecainide or propafenone--the "pill-in-the-pocket" approach--after the onset of heart palpitations was evaluated in the remaining 210 patients (mean age [+/-SD], 59+/-11 years). RESULTS: During a mean follow-up of 15+/-5 months, 165 patients (79 percent) had a total of 618 episodes of arrhythmia; of those episodes, 569 (92 percent) were treated 36+/-93 minutes after the onset of symptoms. Treatment was successful in 534 episodes (94 percent); the time to resolution of symptoms was 113+/-84 minutes. Among the 165 patients with recurrences, the drug was effective during all the arrhythmic episodes in 139 patients (84 percent). Adverse effects were reported during one or more arrhythmic episodes by 12 patients (7 percent), including atrial flutter at a rapid ventricular rate in 1 patient and noncardiac side effects in 11 patients. The numbers of monthly visits to the emergency room and hospitalizations were significantly lower during follow-up than during the year before the target episode (P<0.001 for both comparisons). CONCLUSIONS: In a selected, risk-stratified population of patients with recurrent atrial fibrillation, pill-in-the-pocket treatment is feasible and safe, with a high rate of compliance by patients, a low rate of adverse events, and a marked reduction in emergency room visits and hospital admissions.

Diagnosis of neurally mediated syncope at initial evaluation and with tilt table testing compared with that revealed by prolonged ECG monitoring. An analysis from the Third International Study on Syncope of Uncertain Etiology (ISSUE-3).

OBJECTIVE: According to the guidelines of the European Society of Cardiology, a presumed diagnosis of neurally mediated syncope (NMS) can be made when patients have a consistent history and competing diagnoses are excluded. In the present study, we compared the initial diagnosis of NMS by means of implantable loop recorder (ILR) documentation. METHODS: In this prospective multicentre observational study which involved 51 hospitals in nine countries in Europe and Canada, 504 NMS patients ≥40 years, who had suffered ≥3 syncopal episodes in the previous 2 years received an ILR and were followed up for a mean of 15±11 months. RESULTS: ILR recorded a spontaneous syncope in 187 cases, with an estimated diagnostic yield of 47% at 3 years. ILR findings were consistent with the initial diagnosis of presumed NMS in 162 (87%) patients whereas did not confirm NMS in another 25 (13%), who had an intrinsic cardiac arrhythmic cause (atrial tachyarrhythmias (#6), long pause on termination of tachyarrhythmia (#8), persistent bradycardia (#3), ventricular tachycardia (#4)) or a non-arrhythmic loss of consciousness (non-syncopal (#3), orthostatic hypotension (#1)). No clinical baseline feature was able to predict an intrinsic cardiac cause with the exception of more frequent non-syncopal atrial tachyarrhythmias on clinical history, which were present in 38% of cardiac versus 5% of NMS patients (p=0.001). Tilt table testing (TT) was positive in 76/136 (56%) presumed NMS and in 9/21 (43%) non-NMS patients (p=0.35); an asystolic response was present in 28/136 (21%) NMS and in 0/21 (0%) non-NMS patients (p=0.03). CONCLUSIONS: ILR findings showed results other than NMS in a small, although non-negligible, number of patients older than 40 years. TT was unable to discriminate between presumed NMS and non-NMS with the exception of an asystolic response which was highly specific.

The risk profile for obstructive sleep apnea does not affect the recurrence of atrial fibrillation.

BACKGROUND: Obstructive sleep apnea (OSA) has been linked to increased prevalence and recurrence of atrial fibrillation (AF). We hypothesized that OSA may aggravate AF in patients with pacemakers implanted for sinus bradycardia who had documented paroxysmal AF. METHODS: Seventy-two patients (36 M, aged 77 +/- 6 years) completed the study. All patients received a dual-chamber pacemaker equipped with diagnostic and preventive functions for AF. OSA was diagnosed with the Berlin Questionnaire, which is validated to identify patients with OSA. Four-month continuous pacemaker recordings were collected for all patients. RESULTS: OSA was diagnosed in 28% of patients. Patients at high risk for OSA (HR group) and patients at low risk for OSA (LR group) were equivalent for gender, age, and body mass index. The rate of hypertension was higher in HR than in LR group (90% vs 44%, P < 0.01). The prevalence of paroxysmal AF during the study period was similar in HR and LR group (53% vs 44%, P = NS). Overall number of AF episodes per month was not significantly different between HR and LR group (7 +/- 13 vs 36 +/- 122, P = NS). Similarly, AF burden (AF%) was not significantly different between HR and LR group (0.3 +/- 0.6 vs 2.0 +/- 4.8, P = NS). Circadian distribution of AF episodes was similar in both groups. CONCLUSION: Long-term pacemaker recording of AF recurrence, AF burden, and its circadian distribution is similar in patients with paroxysmal AF at high risk for OSA and those at low risk for OSA.