Biomedical subjects

Andrea Grammatico

Publications and source records attributed to Andrea Grammatico.

11 recordsLinked to original sources

PubMed2006

Design and rationale of a randomized study to compare amiodarone and Class IC anti-arrhythmic drugs in terms of atrial fibrillation treatment efficacy in patients paced for sinus node disease: the PITAGORA trial.

AIMS: Many sinus node disease (SND) patients suffer from atrial fibrillation (AF). Anti-arrhythmic drugs (AADs) are the therapeutic mainstay for AF prophylaxis. The PITAGORA trial has a multicentre, prospective, randomized, single blind design to compare amiodarone with Class IC AADs in patients who have an AF history and are paced for SND. METHODS AND RESULTS: Starting from January 2001, 176 patients received a Medtronic AT500 pacemaker. AADs were randomly assigned with a 3 : 2 ratio between Class III and Class IC. Randomization was stratified in order to assign two patients to amiodarone and one patient to sotalol every three Class III AAD patients. After a 5-month observational period, Ramp or Burst+ ATP therapies were enabled in a randomized way, maintained for 4 months, and then crossed over. Total follow-up period is 21 months. The primary long-term objective is to show the non-inferiority of IC AADs compared with amiodarone in terms of time to first occurrence of a composite endpoint (death, atrial cardioversion, hospitalizations due to AF or heart failure, or change of AADs). Data will be analysed on an intention-to-treat basis. The primary short-term objective is to compare Ramp vs. Burst+ efficacy in terminating atrial tachyarrhythmias treated by the device. Secondary endpoints are major clinical events, medication toxicity, symptoms, AF burden, and quality-of-life. CONCLUSION: Given the high morbidity and healthcare costs associated with AF, new therapeutic strategies are needed. The results of the PITAGORA trial may help in guiding AADs therapy and ATP programming in SND patients suffering from AF.

Amiodarone↗

PubMed2006

Randomized comparison between Ramp and Burst+ atrial antitachycardia pacing therapies in patients suffering from sinus node disease and atrial fibrillation and implanted with a DDDRP device.

AIMS: Atrial tachycardia and flutter frequently occur in association with atrial fibrillation and may be treated by overdrive pacing in patients who receive pacemakers with antitachycardia pacing (ATP) capabilities. The PITAGORA trial was a multi-centre, randomized, cross-over study aimed at comparing two different ATP modes for atrial tachyarrhythmia (AT) termination in patients suffering from sinus node disease (SND). METHODS AND RESULTS: One hundred and seventy-six patients (72 M, age 71+/-9 years) received a Medtronic AT500 pacemaker. All patients were on class IC or III antiarrhythmic drugs. After a 5-month observation period, 170 patients were randomized to either Ramp or Burst+ ATP therapy; 4 months later they crossed over. One hundred and fifty-seven patients completed the 13 months of follow-up; 114 (72.6%) suffered 6088 AT episodes. In 75 patients, 1904 AT episodes were treated and 934 (49.1%) successfully terminated. The median value of individual patients' ATP efficacy was 60%. Burst+ terminated 387 out of 873 AT episodes (44%) in 58 patients. Ramp terminated 547 out of 1031 AT episodes (53%, P<0.001) in 56 patients. Ramp efficacy was significantly (P<0.01) and directly correlated with AT cycle length (ATCL), whereas Burst+ efficacy was not. Ramp showed higher (P<0.001) termination efficacy than Burst+ for ATCL >240 ms. Quality of life, as measured by the EuroQoL questionnaire, and number of symptoms significantly improved in the overall population. This improvement was significantly higher in patients with ATP efficacy >60%. CONCLUSION: In patients suffering from SND and AT, Ramp therapy shows higher termination efficacy than Burst+ therapy in AT episodes with ATCL >240 ms. Further studies are required to show the impact of ATP on clinical outcomes.

Aged↗

PubMed2006

Optimization of pacing algorithms to prevent and treat supraventricular tachyarrhythmias.

Preventive atrial pacing and antitachycardia pacing have been proposed for the treatment of atrial fibrillation and associated arrhythmias in patients with indications for device implantation. Preventive algorithms provide overdrive atrial pacing, reduction of atrial premature beats, and prevent short-long atrial cycles with good patient tolerance. However, clinical trials testing preventive algorithms have shown contradictory results, possibly because of different trial designs, end points and patient populations. Factors probably responsible for neutral results include an already high atrial pacing percentage with the conventional DDDR mode, suboptimal atrial pacing site, and the deleterious effects of high percentages of right ventricular apical pacing. Atrial antitachycardia pacing therapies are effective in treating organized atrial tachyarrhythmias (that precede atrial fibrillation), mainly when delivered early after the onset particularly if the tachycardia is relatively slow. Antitachycardia pacing therapies might influence atrial fibrillation burden, but clinical studies have shown conflicting results about this issue. Consistent monitoring of atrial and ventricular rhythm including progression to persistent forms of atrial arrhythmias, variability of atrial arrhythmia recurrence patterns and onset mechanisms as well as antitachycardia pacing efficacy should be recorded in the stored device memory and used for optimal individual programming of these new functions.

Algorithms↗

PubMed2005

Monitored atrial fibrillation duration predicts arterial embolic events in patients suffering from bradycardia and atrial fibrillation implanted with antitachycardia pacemakers.

OBJECTIVES: The aim of our study was to evaluate arterial embolism (AE) occurrence rates and predictors in patients suffering from bradycardia and wearing a pacemaker with antitachycardia pacing therapies. BACKGROUND: Atrial fibrillation (AF) is associated with a high incidence of AE. METHODS: A total of 725 patients (360 men, age 71 +/- 11 years) were implanted with a DDDRP pacemaker (Medtronic AT500, Medtronic Inc., Minneapolis, Minnesota). At baseline 225 (31.0%) patients received antiplatelet therapy and 264 (36.4%) patients received anticoagulation agents. RESULTS: Over a median 22-month follow-up (25th to 75th interquartile range 16 to 30 months), AE occurred in 14 (1.9%) patients: 7 patients suffered a nonfatal ischemic stroke (0.6% per year), 4 patients had transient ischemic attack (0.34% per year), and 3 patients had embolic complications. Among baseline patients' characteristics, multivariate logistic analysis showed that embolic events are independently associated to ischemic heart disease (7.0 odds ratio [OR], 95% confidence interval [CI] 2.3 to 21.3, p = 0.001), prior embolic event (7.3 OR, 95% CI 1.2 to 43.9, p = 0.029), diabetes (5.0 OR, 95% CI 1.2 to 15.7, p = 0.032), and hypertension (4.1 OR, 95% CI 1.1 to 15.6, p = 0.036). The risk of embolism, adjusted for known risk factors, was 3.1 times increased (95% CI 1.1 to 10.5, p = 0.044) in patients with device-detected atrial fibrillation episodes longer than one day during follow-up. CONCLUSIONS: In a cohort of patients with bradycardia and AF, arterial embolism was common in patients with ischemic cardiopathy, hypertension, diabetes mellitus, and in patients with known stroke risk factors. Atrial fibrillation occurrences longer than one day were independently associated with embolic events.

Aged↗

PubMed2005

Long-term reduction of atrial tachyarrhythmia recurrences in patients paced for bradycardia-tachycardia syndrome.

BACKGROUND: Atrial tachyarrhythmias (AT) are considered progressive diseases. Several rhythm control therapies for treatment of AT have been proposed. OBJECTIVES: The Italian AT500 Registry was designed to prospectively study long-term AT evolution in patients paced for the brady-tachy form of sinus node disease (BT-SND). METHODS: Three hundred forty-six BT-SND patients received an antitachycardia dual-chamber pacemaker and were followed-up for a minimum of 12 months (median 19 months). Prevention and antitachycardia pacing (ATP) features were enabled in all patients. RESULTS: During the observation period, 224 (65%) patients were treated by antiarrhythmic drugs and 45 (13%) patients were cardioverted. Five patients suffered a stroke, 4 transient ischemic attack, 22 permanent AT, and 98 AT recurrences longer than 7 days. AT mean cycle length changed from 246 to 270 ms, and the percentage of patients with AT-related hospitalizations significantly decreased with an annual 28% relative reduction. AT burden and the percentage of patients with AT recurrences longer than 2 days remained constant with time in the overall population but decreased significantly in the subgroup of patients who did not develop permanent AT. High ATP efficacy was associated with an increasingly higher prevention of AT recurrences longer than 2 days. CONCLUSION: In a long-term observation of BT-SND patients, AT-related hospitalizations decreased significantly and mean AT cycle length increased significantly. The data suggest that rhythm control therapies induce inversion of AT progression.

Aged↗

PubMed2005

Predictors of atrial antitachycardia pacing efficacy in patients affected by brady-tachy form of sick sinus syndrome and implanted with a DDDRP device.

UNLABELLED: Predictors of ATP efficacy in brady/tachy patients. BACKGROUND: Recent options to treat atrial tachyarrhythmias (ATA) include implantable devices delivering antitachycardia pacing therapies (ATP). No prospective study selected patients with higher chances of episode termination by ATP or indicated the most effective ATP use. Our aim was to study ATP efficacy in patients with brady-tachy form of sinus node disease (SND), identifying clinical factors, ATA characteristics, and device features predicting ATP efficacy. METHODS AND RESULTS: Three hundred and sixteen patients (105 M, aged 71.1+/-8.8 years) received a DDDRP pacemaker and were prospectively followed. Median follow-up was 18 months: 37,125 ATA episodes occurred in 217 patients; ATP treated 5,536 of them. Overall, ATP efficacy was 50.0%. A multivariate analysis identified longer arrhythmia cycle lengths (OR=1.25; CI=1.07-1.47) and shorter delays to ATP delivery (OR=0.15; CI=0.10-0.22) as independent predictors of ATP efficacy for episodes preceded by >or=5 minutes of sinus rhythm. Additionally, ATP efficacy for all treated episodes was predicted by lower New York Heart Association (NYHA) class (OR=0.64; CI=0.42-0.98), episode classification as nonimmediate recurrence of ATA (non-IRAT) (OR=0.07; CI=0.02-0.33), absence of overlap in the device detection windows (OR=0.54; CI=0.32-0.91), and flecainide treatment (OR=2.22; CI=1.04-4.71). CONCLUSIONS: In patients paced for SND, multivariate analysis shows that ATP efficacy is associated to longer arrhythmia cycle lengths, shorter ATP delivery delays, NYHA class I, episode classification as non-IRAT, absence of overlap in the atrial arrhythmia device detection windows, and flecainide treatment.

Aged↗

PubMed2004

Temporal variability of atrial tachyarrhythmia burden in bradycardia-tachycardia syndrome patients.

AIMS: Several studies have tested non-pharmacological therapies for atrial tachyarrhythmias (ATs) by measuring the cumulative time (burden) the patient spends in arrhythmia. Contradictory results questioned either therapy efficacy or statistical power of the trials. We studied AT burden variability in patients paced for sinus node disease (SND) in order to interpret currently published data appropriately and to evaluate reliable sample sizes. METHODS AND RESULTS: One hundred and five patients with AT and SND received a dual chamber pacemaker with antitachyarrhythmia-pacing capability, and were followed for 13 months. Seventy-eight patients (74%) suffered AT recurrences. Device-gathered diagnostic measures were used to simulate results of randomized studies both with crossover and parallel design. The sample size required for statistically significant results was calculated as a function of the expected therapy-induced burden reduction. AT burden intra-patient variability was high: 43% of patients showed intrinsic fluctuations hiding any therapy-induced burden reduction lower than 30%. Demonstrating therapeutic breakthrough through a 6 month study would require 290 patients with crossover design and 5800 patients with parallel design. Doubling the study period requires 400 and 3000 patients, respectively. CONCLUSION: Patients with AT and paced for SND showed high intra-patient burden variability, which could possibly hide an AT burden reduction induced by a therapy. Previous studies involving non-pharmacological therapies utilizing AT burden endpoints could lack the power to reach statistical significance.

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PubMed2004

Sample size estimates for atrial fibrillation endpoints.

This article reviews the current sample size requirements for studies evaluating the efficacy of atrial therapies. Sample sizes for several study designs and endpoints are presented. However, emphasis is given to studies conducted in patients with implantable devices in the light of new available data from recent trials involving such patients. Studies utilizing mortality require >5,000 patients followed for at least 2 years. Symptomatic episode recurrence represents a possible alternate endpoint but still requires >400 patients followed for 1 year. Parallel design studies for device atrial fibrillation (AF) burden and frequency endpoints were found to be of little value because they would require thousands of patients. In contrast, cross-over studies utilizing device AF burden or AF frequency endpoints provide the best option in terms of sample size and study duration. A 30% therapy efficacy (reduction in AF burden or frequency) can be detected with just a little over 100 patients followed for 6 months. Therefore, cross-over studies with device-based endpoints are a viable option to evaluate and screen possible new rhythm control treatments before evaluating their effect on clinical outcome variables that may require larger trials with longer follow-up times.

Atrial Fibrillation↗

PubMed2004

Atrial tachyarrhythmia recurrence temporal patterns in bradycardia patients implanted with antitachycardia pacemakers.

INTRODUCTION: New-generation pacemakers allow continuous atrial tachyarrhythmia (AT) monitoring that provides accurate information about AT type, frequency, burden, and temporary evolution. METHODS AND RESULTS: We performed a prospective multicenter study to describe AT temporal patterns in patients with sinus bradycardia and AT. Two hundred forty patients (123 men; age 71 +/- 8 years) were implanted with a DDDRP pacemaker (model AT500, Medtronic Inc.). All patients were followed for 13 months. The first-month stabilization period of all patients was discarded from analysis. Seventy percent of patients had AT recurrences. Mean time to first AT recurrence (48.2 days, 95% confidence interval [CI] 37.0-59.5 days) was significantly longer than the time between first and second AT episode (10.3 days, 95% CI 6.7-13.9 days, P < 0.01). A minority of patients had a uniform time distribution of AT recurrences: <25% of patients had AT episodes in more than 6 of the 12 months considered in the study. The probability density function of consecutive sinus rhythm days between AT episodes was calculated for each of 40 patients who experienced >25 AT episodes and fitted by power law and exponential functions. The best fit was obtained by power law function in 60% of patients, by exponential function in 10%, and the two models gave comparable results in 30% of patients. CONCLUSION: In our population of patients with a history of sinus bradycardia and AT who were implanted with a new device equipped with atrial pacing therapies, 30% did not experience AT recurrences in the 12-month study period. Analysis of interevent time showed that in 60% of patients AT recurrences do not follow a uniform or random distribution. These findings bring into question the use of cross-over design and time to first AT recurrence as a clinical outcome in trials for AT therapy in this patient population.

Adult↗

PubMed2004

Far-field R wave oversensing in dual chamber pacemakers designed for atrial arrhythmia management: effect of pacing site and lead tip to ring distance.

INAMA, G., et al.: Far-Field R Wave Oversensing in Dual Chamber Pacemakers Designed for Atrial Arrhythmia Management: Effect of Pacing Site and Lead Tip to Ring Distance. The aim of the study was to determine the incidence and practical implications of far-field R wave oversensing (FFRWO) and its association with pacing site and lead tip to ring spacing (TTRS) in implantable devices designed to diagnose and treat atrial tachyarrhythmias and programmed with a fixed and short postventricular blanking period. The study included 395 patients who were implanted with a DDDRP pacemaker and prospectively followed. At implant and follow-up visits FFRWO was assessed by analyzing lead electrical measures and atrial tachyarrhythmic episodes collected in the device diagnostics. During a median follow-up of 12 months 11 (2.8%) of 395 patients showed a clinically significant FFRWO that induced inappropriate detection or pacemaker malfunctioning. The atrial pacing site of these 11 patients was right atrium appendage (RAA) for 3 patients, representing 1.1% of 254 RAA patients, coronary sinus ostium (CSO) for 7 patients, representing 7.4% of 94 CSO patients (P < 0.005 vs RAA), and lateral wall (LW) for 1 (2.9%) of 34 LW patients. The minimal value of the FFRWO to P wave ratio, measured at implant, associated with a clinically significant FFRWO was 0.6; therefore, a value of 0.5 was used as a cutoff to identify patients at risk of undesirable device behavior induced by FFRWO: there were 11 (9.6%) of 114 of RAA patients with short (< or = 10 mm) TTRS, 22 (18.8%) of 117 of RAA patients with long (> or = 17 mm) TTRS (P < 0.05 vs short TTRS), 21 (30.6%) of 64 of CSO patients short TTRS (P < 0.001 vs RAA patients with short TTRS) and 3 (30%) of 10 of CSO patients with long TTRS. The analysis showed that, despite the short postventricular blanking time, FFRWO inducing undesired functioning in AT500 pacemakers is infrequent (2.8% of patients). Compared to RAA, the CSO lead position was more frequently associated with FFRWO.TTRS < 10 mm was associated with lower risk of clinically significant FFRWO in RAA. (PACE 2004; 27:1221-1230).

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PubMed2003

Prevention of paroxysmal atrial fibrillation in patients with sinus bradycardia: role of right atrial linear ablation and pacing site.

INTRODUCTION: Right atrial linear lesions (RALL), either alone or in combination with antiarrhythmic drug therapy, may modify the substrate for maintenance of atrial fibrillation (AF). The aim of this prospective randomized study was to determine whether RALL provides additional benefit to right atrial appendage pacing (RAAP) and/or interatrial septum pacing (IASP) and drug therapy in patients with symptomatic paroxysmal AF and sinus bradycardia requiring permanent atrial pacing. METHODS AND RESULTS: Sixty-four patients (33 men and 31 women, mean age 73 +/- 10 years) completed the 6-month follow-up. Patients were randomized to either RALL (n = 33) or non-right atrial linear lesions (NRALL), and then to either IASP (n = 32) or RAAP (n = 32). Fifteen RALL patients were paced at the IAS and 18 at the RAA. Seventeen NRALL patients were paced at the IAS and 14 at the RAA. No statistical difference was observed with regard to the mean atrial tachyarrhythmia (AT) burden between NRALL (84 +/- 169 min/day) and RALL patients (202 +/- 219 min/day). Mean AT burden was significantly lower in the IASP group (70 +/- 150 min/day) than in RAAP group (219 +/- 317 min/day; P < 0.016). In the RALL group, the mean AT burden was 99 +/- 180 min/day in the IASP patients and 288 +/- 372 min/day in the RAAP patients (P < 0.046). In the NRALL group, no statistical difference in the mean AT burden was observed between IASP patients (46 +/- 117 min/day) and RAAP patients (130 +/- 211 min/day). CONCLUSION: The results of the present study indicate that RALL did not provide any additional therapeutic benefit to combined antiarrhythmic drug therapy and septal or nonseptal atrial pacing in patients with sinus bradycardia and paroxysmal AF.

Aged↗