Maria Teresa Fernández Cáceres1, Ana Cristina P. P. Ludovice2, Fabio Sândoli de Brito2, Francisco Carlos Darrieux1, Ricardo Simões Neves1, Mauricio Ibrahim Scanavacca1,2, Eduardo A. Sosa1,2, Denise Tessariol Hachul1,2
Instituto do Coração do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (FMUSP)1, Hospital Albert Einstein2, São Paulo, SP - Brasil
Resumo
Fundamento: A utilização de anestésicos locais associados a vasoconstritores para tratamento odontológico de rotina de pacientes cardiopatas ainda gera controvérsia, em razão do risco de efeitos cardiovasculares adversos.
Objetivo: Avaliar e comparar os efeitos hemodinâmicos do uso de anestésico local com vasoconstritor não-adrenérgico em pacientes portadores de arritmias ventriculares, em relação ao uso de anestésico sem vasoconstritor.
Métodos: Um estudo prospectivo randomizado avaliou 33 pacientes com sorologia positiva para doença de Chagas’ e 32 pacientes com doença arterial coronariana, portadores de arritmia ventricular complexa ao Holter (>10 EV/h e TVNS), 21 do sexo feminino, idade de 54,73 + 7,94 anos, submetidos a tratamento odontológico de rotina com anestesia pterigomandibular. Esses pacientes foram divididos em dois grupos: no grupo I, utilizou-se prilocaína a 3% associada a felipressina 0,03 UI/ml, e no grupo II, lidocaína a 2% sem vasoconstritor. Avaliaram-se o número e a complexidade de extra-sístoles, a freqüência cardíaca e a pressão arterial sistêmica dos pacientes no dia anterior, uma hora antes, durante o procedimento odontológico e uma hora após.
Resultados: Não foram observadas alterações hemodinâmicas, nem aumento do número e da complexidade da arritmia ventricular, relacionados ao anestésico utilizado, em ambos os grupos.
Conclusão: Os resultados sugerem que prilocaína a 3% associada a felipressina 0,03 UI/ml pode ser utilizada com segurança em pacientes chagásicos e coronarianos, com arritmia ventricular complexa. (Arq Bras Cardiol 2008;91(3):142-147)
Palavras-chave: Arritmias cardíacas, anestésicos locais, vasoconstritores, cardiomiopatia chagásica, doença das coronárias.
segunda-feira, 15 de setembro de 2008
domingo, 14 de setembro de 2008
Ablation for Atrial Fibrillation Best Course After Failed Antiarrhythmic Drug Therapy: The Results of the A4 Trial
Medscape CRM News 2006. © 2006 Medscape
"We now have proof that in [paroxysmal AF] patients in whom at least one drug has failed to control their AF, ablation performs much better than trying additional drugs. This holds true even for the most powerful antiarrhythmic drug, amiodarone" -- Pierre Jais, MD (Hôpital Cardiologique Haut-Leveque Bordeaux-Pessac, France)
In patients with symptomatic, paroxysmal atrial fibrillation (AF) who have already failed at least 1 attempt at antiarrhythmic drug (AAD) therapy, catheter ablation may be a better treatment choice than switching to another drug, according to the results of the Atrial Fibrillation vs Antiarrhythmic Drugs (A4)[1] trial.
A4 Investigators reported that compared with patients who were randomized to AADs, patients who received ablation therapy were much less likely to experience an episode of AF over a 12-month follow-up period and also demonstrated better exercise capacity and quality-of-life scores.
The results add to the positive evidence from other recent studies of AF catheter ablation, including 2 trials released earlier this year from Carlo Pappone, MD, PhD and colleagues (San Raffaele University Hospital, Milan, Italy), demonstrating the superiority of ablation vs AADs for maintaining normal sinus rhythm in patients with both paroxysmal and chronic AF (see Related Links).[2,3]
Pierre Jais, MD, of Hôpital Cardiologique Haut-Leveque (Bordeaux-Pessac, France), who presented the results of A4 at Heart Rhythm Society (HRS) 2006 Annual Scientific Sessions, said the results were crystal clear. "We now have proof that in [paroxysmal AF] patients in whom at least one drug has failed to control their AF, ablation performs much better than trying additional drugs. This holds true even for the most powerful antiarrhythmic drug, amiodarone," he asserted.
A4: Study Design and Methods
A4, which was conducted at 4 centers in Europe and North America, randomized 112 patients to receive either AAD therapy (n = 59) or ablation (n = 53). Patients had to have symptomatic, paroxysmal AF of at least 6 months' duration with at least 2 AF episodes per month, and resistance to at least 1 Class I or III AAD. The average age of the participants was 51 years, and 85% were male; the mean duration of AF episodes at baseline was 9 ± 9 hours; and 80% of patients were on anticoagulant drugs.
Patients were followed at 2, 3, 6, and 12 months using 24-hour Holter monitoring as well as patient-kept diaries. The primary endpoint, recurrence of AF, was defined as any episode of arrhythmia beyond Month 3 (documented or not) lasting more than 3 minutes. Secondary endpoints included quality-of-life scores, withdrawal of anticoagulation at 1 year, and adverse events/mortality.
The first 3 months of the trial were designated as a "blanking period" during which patients in the drug group were allowed to receive up to 3 different AADs, either alone or in combination, and those in the ablation group were allowed up to 3 ablation procedures. Repeat ablations were common, with a mean of 1.8 ablations performed per patient in this group. Circumferential pulmonary vein isolation was performed in all ablation patients, with additional focal or linear ablation lines placed as needed.
After 3 months, the patients were assessed for the primary and secondary endpoints and crossover was permitted if needed. Crossovers were common in the AAD group, with a total of 37 AAD patients who failed drug therapy crossing over to the ablation group by study end.
In his presentation, Dr. Jais conceded that the definition they used for AF recurrence was very strict and probably resulted in an overestimation of the number of treatment failures in the study. However, he explained that because of the lack of published data on the success rate of AADs in paroxysmal AF patients, the investigators had to define their own criteria for success and failure and thus decided to embrace a strict definition.
Results
The results are summarized in the table below. At 1-year follow-up, 75% of the ablation group was free of arrhythmia recurrence, compared with only 7% of the AAD group. Moreover, 60% of the ablation patients were able to discontinue oral anticoagulation therapy, compared with 25% in the AAD group who did not cross over. The Kaplan-Meier plots for time to AF recurrence also showed a highly statistically significant superiority of ablation over AADs (P < .0001). Patients who were treated with amiodarone for the first time during the trial achieved a slightly better result than the overall outcomes in the AAD group, with 21% of the first-time amiodarone patients being free from AF recurrence at 12 months. However, this was still far inferior to what was achieved in the ablation group.
The majority of the quality-of-life results also were significantly better in the ablation group, and these findings were maintained over the 12-month follow-up period. In addition, a 12-month stress test showed significantly greater improvement in the ablation group in several measures of functionality, including exercise duration and maximum systolic blood pressure.
Complications in the ablation group included 2 tamponades (including 1 reported in a crossover patient), 2 groin hematomas, and 1 pulmonary vein stenosis, while AAD complications included 1 patient with hyperthyroidism and 1 death due to cancer, which was probably not related to the AAD. No stroke or transient ischemic attacks were observed in either group over the 12-month follow-up.
The researchers concluded that in patients who have failed at least 1 AAD, AF ablation results in a far better outcome compared with those seen with other AADs. They called for further study to compare the impact of both strategies on a longer-term outcome.
Table. A4: Primary and Secondary Endpoints at 12 Months
Outcome Ablation Group
(n = 53) AAD Group
(n = 59) P
Free of arrhythmia recurrence at 1 year (%) 75 7 --
Discontinued oral anticoagulation (%) 60 25* --
Quality-of-life measures (intention-to-treat basis):
Physical function 91.3 82.2 .0012
Social function 90.4 80.9 .0024
Mental health 90.7 80.6 .0018
Physical component 52.0 48.9 .0174
Mental component 56.6 51.9 .0106
*Of the 22 patients who did not cross over to ablation group
Discussion, Limitations, and Future Technology
Following the presentation, session moderator A. John Camm, MD (St. George's Hospital Medical School, London, United Kingdom), questioned the study's design and asked whether such a soft endpoint that included palpitations of only 3 minutes' duration should be considered a true endpoint. He noted that it would be helpful if the trial were continued to collect more hard-endpoint data. Responding to the comments, Dr. Jais acknowledged that the study had limitations, but said the investigators had determined that continuation of the trial was not realistic because patients who fail drug therapy may want to have an ablation procedure and "they will not accept a trial where they cannot cross over."
Dr. Jais stressed the importance of proper patient selection for AF ablation, pointing out that ablation therapy can only be justified in symptomatic patients with a significant AF burden. "It probably doesn't make sense to offer ablation therapy for patients who have only 2 AF episodes per year," he said. "Ablation is not 100% safe. . . you have to keep in mind that you do have complications with this procedure." On the other hand, the trial clearly suggests that "if a patient fails one AAD, it doesn't make sense to try all the other available drugs because the chance of success is very low," he pointed out. In this case, he concluded, "physicians should consider going on to perform ablation, providing the patient has a minimal degree of AF."
AF ablation was a topic of great interest at this year's HRS meeting, which kicked off on Wednesday, May 17th, with a live, satellite-linked, transatlantic AF ablation case performed by Dr. Pappone that wowed attendees. Working from a lab in Boston, Massachusetts, Dr. Pappone used remote magnetic navigation technology and robotic controls to perform catheter-based, circumferential pulmonary vein ablation on a patient located in Milan, Italy. Marking the first public demonstration of such a feat, the procedure was successfully completed in about 1 hour in front of hundreds of rapt observers. Despite significant cost concerns, some contend that the use of the remote robotic technology can be used to educate other electrophysiologists on procedural techniques at different centers worldwide, and that the use of this technology may offer better clinical outcomes than those obtained using manual navigation.
Supported by an independent educational grant from St. Jude Medical.
"We now have proof that in [paroxysmal AF] patients in whom at least one drug has failed to control their AF, ablation performs much better than trying additional drugs. This holds true even for the most powerful antiarrhythmic drug, amiodarone" -- Pierre Jais, MD (Hôpital Cardiologique Haut-Leveque Bordeaux-Pessac, France)
In patients with symptomatic, paroxysmal atrial fibrillation (AF) who have already failed at least 1 attempt at antiarrhythmic drug (AAD) therapy, catheter ablation may be a better treatment choice than switching to another drug, according to the results of the Atrial Fibrillation vs Antiarrhythmic Drugs (A4)[1] trial.
A4 Investigators reported that compared with patients who were randomized to AADs, patients who received ablation therapy were much less likely to experience an episode of AF over a 12-month follow-up period and also demonstrated better exercise capacity and quality-of-life scores.
The results add to the positive evidence from other recent studies of AF catheter ablation, including 2 trials released earlier this year from Carlo Pappone, MD, PhD and colleagues (San Raffaele University Hospital, Milan, Italy), demonstrating the superiority of ablation vs AADs for maintaining normal sinus rhythm in patients with both paroxysmal and chronic AF (see Related Links).[2,3]
Pierre Jais, MD, of Hôpital Cardiologique Haut-Leveque (Bordeaux-Pessac, France), who presented the results of A4 at Heart Rhythm Society (HRS) 2006 Annual Scientific Sessions, said the results were crystal clear. "We now have proof that in [paroxysmal AF] patients in whom at least one drug has failed to control their AF, ablation performs much better than trying additional drugs. This holds true even for the most powerful antiarrhythmic drug, amiodarone," he asserted.
A4: Study Design and Methods
A4, which was conducted at 4 centers in Europe and North America, randomized 112 patients to receive either AAD therapy (n = 59) or ablation (n = 53). Patients had to have symptomatic, paroxysmal AF of at least 6 months' duration with at least 2 AF episodes per month, and resistance to at least 1 Class I or III AAD. The average age of the participants was 51 years, and 85% were male; the mean duration of AF episodes at baseline was 9 ± 9 hours; and 80% of patients were on anticoagulant drugs.
Patients were followed at 2, 3, 6, and 12 months using 24-hour Holter monitoring as well as patient-kept diaries. The primary endpoint, recurrence of AF, was defined as any episode of arrhythmia beyond Month 3 (documented or not) lasting more than 3 minutes. Secondary endpoints included quality-of-life scores, withdrawal of anticoagulation at 1 year, and adverse events/mortality.
The first 3 months of the trial were designated as a "blanking period" during which patients in the drug group were allowed to receive up to 3 different AADs, either alone or in combination, and those in the ablation group were allowed up to 3 ablation procedures. Repeat ablations were common, with a mean of 1.8 ablations performed per patient in this group. Circumferential pulmonary vein isolation was performed in all ablation patients, with additional focal or linear ablation lines placed as needed.
After 3 months, the patients were assessed for the primary and secondary endpoints and crossover was permitted if needed. Crossovers were common in the AAD group, with a total of 37 AAD patients who failed drug therapy crossing over to the ablation group by study end.
In his presentation, Dr. Jais conceded that the definition they used for AF recurrence was very strict and probably resulted in an overestimation of the number of treatment failures in the study. However, he explained that because of the lack of published data on the success rate of AADs in paroxysmal AF patients, the investigators had to define their own criteria for success and failure and thus decided to embrace a strict definition.
Results
The results are summarized in the table below. At 1-year follow-up, 75% of the ablation group was free of arrhythmia recurrence, compared with only 7% of the AAD group. Moreover, 60% of the ablation patients were able to discontinue oral anticoagulation therapy, compared with 25% in the AAD group who did not cross over. The Kaplan-Meier plots for time to AF recurrence also showed a highly statistically significant superiority of ablation over AADs (P < .0001). Patients who were treated with amiodarone for the first time during the trial achieved a slightly better result than the overall outcomes in the AAD group, with 21% of the first-time amiodarone patients being free from AF recurrence at 12 months. However, this was still far inferior to what was achieved in the ablation group.
The majority of the quality-of-life results also were significantly better in the ablation group, and these findings were maintained over the 12-month follow-up period. In addition, a 12-month stress test showed significantly greater improvement in the ablation group in several measures of functionality, including exercise duration and maximum systolic blood pressure.
Complications in the ablation group included 2 tamponades (including 1 reported in a crossover patient), 2 groin hematomas, and 1 pulmonary vein stenosis, while AAD complications included 1 patient with hyperthyroidism and 1 death due to cancer, which was probably not related to the AAD. No stroke or transient ischemic attacks were observed in either group over the 12-month follow-up.
The researchers concluded that in patients who have failed at least 1 AAD, AF ablation results in a far better outcome compared with those seen with other AADs. They called for further study to compare the impact of both strategies on a longer-term outcome.
Table. A4: Primary and Secondary Endpoints at 12 Months
Outcome Ablation Group
(n = 53) AAD Group
(n = 59) P
Free of arrhythmia recurrence at 1 year (%) 75 7 --
Discontinued oral anticoagulation (%) 60 25* --
Quality-of-life measures (intention-to-treat basis):
Physical function 91.3 82.2 .0012
Social function 90.4 80.9 .0024
Mental health 90.7 80.6 .0018
Physical component 52.0 48.9 .0174
Mental component 56.6 51.9 .0106
*Of the 22 patients who did not cross over to ablation group
Discussion, Limitations, and Future Technology
Following the presentation, session moderator A. John Camm, MD (St. George's Hospital Medical School, London, United Kingdom), questioned the study's design and asked whether such a soft endpoint that included palpitations of only 3 minutes' duration should be considered a true endpoint. He noted that it would be helpful if the trial were continued to collect more hard-endpoint data. Responding to the comments, Dr. Jais acknowledged that the study had limitations, but said the investigators had determined that continuation of the trial was not realistic because patients who fail drug therapy may want to have an ablation procedure and "they will not accept a trial where they cannot cross over."
Dr. Jais stressed the importance of proper patient selection for AF ablation, pointing out that ablation therapy can only be justified in symptomatic patients with a significant AF burden. "It probably doesn't make sense to offer ablation therapy for patients who have only 2 AF episodes per year," he said. "Ablation is not 100% safe. . . you have to keep in mind that you do have complications with this procedure." On the other hand, the trial clearly suggests that "if a patient fails one AAD, it doesn't make sense to try all the other available drugs because the chance of success is very low," he pointed out. In this case, he concluded, "physicians should consider going on to perform ablation, providing the patient has a minimal degree of AF."
AF ablation was a topic of great interest at this year's HRS meeting, which kicked off on Wednesday, May 17th, with a live, satellite-linked, transatlantic AF ablation case performed by Dr. Pappone that wowed attendees. Working from a lab in Boston, Massachusetts, Dr. Pappone used remote magnetic navigation technology and robotic controls to perform catheter-based, circumferential pulmonary vein ablation on a patient located in Milan, Italy. Marking the first public demonstration of such a feat, the procedure was successfully completed in about 1 hour in front of hundreds of rapt observers. Despite significant cost concerns, some contend that the use of the remote robotic technology can be used to educate other electrophysiologists on procedural techniques at different centers worldwide, and that the use of this technology may offer better clinical outcomes than those obtained using manual navigation.
Supported by an independent educational grant from St. Jude Medical.
Asymptomatic Atrial Fibrillation in Pacemaker Recipients: Incidence, Progression, and Determinants Based on the Atrial High Rate Trial
Michael V. Orlov, M.D, Ph.D.; Jalal K. Ghali, M.D.; Mohsen Araghi-Niknam, Ph.D.; Lou Sherfesee, Ph.D.; Diane Sahr, R.N., B.S.N.; Douglas A. Hettrick, Ph.D.; for the Atrial High Rate Trial Investigators
Pacing Clin Electrophysiol. 2007;30(3):404-411. ©2007 Blackwell Publishing
Abstract
Background: The epidemiology and clinical implications of asymptomatic atrial tachyarrhythmias (AT) including both atrial fibrillation and flutter in pacemaker recipients with and without arrhythmia history are not well understood. The Atrial High Rate Episodes (A-HIRATE) in Pacemaker Patients Trial was designed to identify and compare the incidence of AT in patients with and without previously diagnosed AT and a standard indication for dual chamber pacing, and to provide useful diagnostic information for clinical management.
Methods: Four hundred twenty-seven patients were implanted with a pacemaker (Kappa 7-900, Medtronic, Inc., Minneapolis, MN, USA) capable of detecting and storing multiple atrial high rate episodes (AHRE) and followed for 2 years. Group I included 331 patients without prior history of AT and Group II included 96 patients with prior AT history.
Results: Pacemaker diagnostics appropriately detected 93% of reviewed AHRE. The rate of occurrence of first AHRE was significantly higher (P < 0.0001) in Group II patients, as was average AHRE burden. The rate of first AHRE occurrence was 88.6% for patients in Group II and 53.8% in Group I at 24 months post-implant. The rate of AHRE occurrence was similar in both groups after the first month post-implant. The majority of stored AHRE were asymptomatic; symptoms did not correspond to an actual AHRE in most patients.
Conclusions: The incidence of AT in pacemaker recipients is high. Most device-detected AHRE are asymptomatic. Prior history of AT is associated with higher arrhythmia burden. AHRE diagnostics have a high positive predictive value for identifying AT events.
Introduction
Atrial tachyarrhythmias (AT), including atrial fibrillation (AF) and flutter, occur frequently in the general population and are responsible for considerable morbidity and mortality, primarily related to stroke.[1-3] According to US Medicare data, the risk of one-year stroke occurrence more than doubled in patients with AT compared to those without AT.[3] AT also accounts for the majority of hospital admissions with arrhythmia as the primary diagnosis.[3,4] However, these reports are based primarily on symptomatic AF and thus allow correlation with subsequent complications. In contrast, the importance of more difficult to detect asymptomatic atrial arrhythmias was underestimated until recently[5,6] and its relevance to morbidity and mortality is less well known. Recently, the introduction of pacemakers with capacity to detect, quantify, and store asymptomatic AT episodes has resulted in new insights into minimally symptomatic AT.[7-10] The epidemiology and clinical implications of this arrhythmia have been studied in pacemaker recipients with prior history of AT.[10] However, despite these recent advances, the importance of asymptomatic AT in clinical practice remains less clear than that of symptomatic AT.
The purpose of the Atrial High Rate Episodes (A-HIRATE) in Pacemaker Patients Trial was to identify the incidence of AT in patients with previously undiagnosed AT and a standard indication for dual chamber pacing, and to provide useful diagnostic information for successful clinical management.
Methods
The A-HIRATE Trial was a multicenter, prospective study assessing the incidence of atrial high rate episodes (AHRE) in pacemaker patients with and without previously diagnosed AT. The trial was conducted in 44 centers in the US, Australia, and France. Each institutional review board approved the study protocol and each participant provided written informed consent. Patients were followed for two years including scheduled follow-up visits at 1, 6, 12, 18, and 24 months. The first patient was enrolled in July of 2000 and the trial was completed in August of 2004. The study consisted of two arms: Group I included patients without previously diagnosed AT and Group II consisted of patients with a prior history of AT as indicated by the enrolling center. Patients in both study arms were required to have an approved indication for pacemaker implantation.[11] The study aimed to determine the incidence of asymptomatic and symptomatic AT, arrhythmia onset characteristics, cumulative AT burden (i.e. cumulative AT episode duration), and to examine the accuracy of AHRE diagnostics. Dual chamber multiprogrammable pacemakers, (Kappa 700 or Kappa 900, Medtronic, Inc., Minneapolis, MN, USA) were implanted in all trial participants. No specific treatments or therapies were required.
Patients were required to program the Atrial High Rate Diagnostic and Clinician Selected Atrial High Rate Detail "ON." The Atrial High Rate Diagnostic records both AHRE summary information and specific episode information. The summary information includes AHRE counts, as well as the percentage of time during the collection period that an AHRE was detected (i.e. "burden"). Specific AHRE information in the Atrial High Rate Diagnostic includes the date, time, and duration of each episode for up to 16 episodes as follows: the Kappa 700 recorded data for the most recent 14 episodes plus the first, fastest, and longest episodes, while the Kappa 900 device recorded data from the most recent 13 episodes plus the first, fastest, and longest episodes. The Atrial High Rate Detail collected device marker channel and beat-to-beat data for up to eight atrial episodes, as well as daily activity recorded in the Atrial Arrhythmia Trend including data on pre-onset events, post-onset events, and pre-termination events. Kappa 900 devices also recorded the cumulative daily AHRE burden (hours/day) for up to 175 consecutive days.
Mode Switch was programmed ON with a 60-second delay in order to avoid detection of non-sustained AT episodes. Decreases in the recommended programmed mode switch delay were allowed in the event of symptomatic AT. An AHRE was defined via device programming as an atrial rate >180 bpm. The minimal episode duration for AHRE detection was programmed to 60 seconds since shorter episodes have questionable clinical significance and are also more likely to be inappropriately detected episodes.[12] Persistent AT was defined as at least seven consecutive days with device classified AHRE burden greater than 22 hours/day. Device programming parameters were recorded at the time of implant and at each follow-up visit. Stored device data including electrograms and the Atrial High Rate Diagnostic data were collected at each follow-up visit. AHRE burden was determined by the device as the cumulative duration of all AHRE divided by the follow-up period. Onset of stored AHRE was classified as bradycardia if the atrial rate was less than 80 bpm and classified as tachycardia if the rate was greater than 80 bpm. A subset of sequentially received device-stored episodes including atrial electrogram and marker channel were reviewed according to prospectively determined criteria in order to validate the accuracy of AHRE detection as previously described.[13]
Patients were issued symptom diaries to record AT symptoms including: "heart fluttering," "skipping," "racing," " light-headedness," "dizziness," "fainting," "chest pain/pressure or fullness," "shortness of breath," and "fatigue," respectively. A symptomatic event was defined as a device-detected AHRE occurring on the same day as patient-reported symptoms. The number of symptomatic episodes per patient-month was determined for each patient by dividing the number of symptomatic episodes for the patient by the total device-measured follow-up period.
Statistical Methods
Fisher's exact test was used to compare demographics between the two groups for qualitative measures, while a t-test was used to compare quantitative measures. Time to first device documented AHRE was compared via AT-free survival analysis by the Kaplan-Meier method for each AT arm. The one-year point estimate and corresponding 95% confidence interval were generated for each arm, and a Log rank test was performed to compare the rate of first occurrence or first recurrence between the two arms. A similar analysis was performed comparing time between a patient's first and second device-detected episodes between the two arms. For the analysis of AHRE burden, a bootstrap confidence interval[14] on the difference in mean burden between the two arms was applied because of the observed non-normal distribution of the burden data. A similar method was used in the analysis of symptomatic episodes. A bootstrap confidence interval on the difference in mean symptomatic episodes per patient month between the two arms was then calculated. Predictors of AHRE occurrence were determined using univariate analyses in the group without prior AT history. All quantitative demographic data are reported as mean ± SD unless indicated. A P-value <0.05 was considered significant.
Results
Recorded data from 427 of the 453 enrolled patients were analyzed, including 331 in the group without prior history of AT (Group I) and 96 patients in the prior AT history group (Group II). Twenty-six patients were excluded from the analysis cohort due to the presence of an ICD or active antiarrhythmic drug therapy at enrollment (Group I). The full 24-month follow-up period was completed by 312 of the patients. Demographic data for both groups are compared in Table 1 . The group with AT history included significantly more females than the primary arm. Patients with AT history had a higher prevalence of sinus node dysfunction, lower prevalence of atrioventricular (AV) block, and higher New York Heart Association (NYHA) Class. In patients with a history of AT, structural heart disease, as defined by coronary artery disease, was more common, while ejection fraction did not differ between groups. There were 32 deaths during the study follow-up period (approximately 7.3% in each group).
The hazard rate of first device-detected AHRE occurrence was significantly higher in patients with history of AT (Figure 1) compared to those without a history of diagnosed AT (P < 0.0001). At 12 and 24 months post-implant, the estimated Kaplan-Meier AHRE-free survival rates for patients with a history of AT were 22.6% and 11.4%, respectively. In the arm without prior AT history, a total of 159 out of 331 patients experienced at least one AHRE; the AHRE-free rates for this patient group were 59.2% and 46.2% at 12 and 24 months post-implant, respectively. Patients in the AT history group were also significantly more likely to experience a second AHRE reoccurrence. The 24-month survival free rate from device-detected AHRE was 42.1% (95% CI: 34.3-51.6%) for the 182 patients with no history of AT and a primary device indication of conduction block and 49.0% (95% CI: 40.3-59.5%) for the 119 patients with no AT history and sinus node dysfunction (P = 0.3). The 24-month AHRE survival rate for the remaining 30 patients with an indication other than SND or AV block was 56.6% (95% CI: 40.4-79.2%). AHRE burden throughout follow-up was significantly higher in the AT history group. The average burden over all follow-up in patients with no history of AT was 0.6 hours per day, compared to 4.4 hours per day among patients with a history of AT (Figure 2). A two-sided bias-corrected 95% bootstrap confidence interval on the average (AT history-no AT history) difference in AHRE burden over all follow-up was determined to be (2.23-5.55 hours per day). Since the interval does not contain 0, it was concluded that patients with AT history have greater AHRE burden than those without. Of the 156 patients in the analysis cohort with Kappa 900 devices, 25 met the prescribed criteria for persistent AT during follow-up, including 20 (26.3%) from the group with AT history and 5 (6.3%) in the group with no AT history.
Discussion
The principal findings of this study are as follows: the incidence of AT in pacemaker recipients is high, as 89% of patients with and 46% of patients without prior AT history experienced a sustained AHRE by 24 months. Prior history of AT is associated with higher arrhythmia burden, which has a non-normal distribution. Most device-detected AHRE are asymptomatic. Symptomatic AT episodes are more common in patients with prior AT but overall incidence of symptomatic AT is quite low. The positive predictive value of the Atrial High Rate Diagnostic is high.
The correlation between AHRE and actual AT events may have important clinical implications. Pollack et al[15] have demonstrated a high correlation (88%) between episodes classified by pacemaker as AHRE and intracardiac electrograms (EGMs). In the ancillary MOST analysis, an excellent correlation between AHRE and AT was provided by Holter monitoring, albeit in a small subset of patients.[16] Other studies have also demonstrated high sensitivity and specificity of pacemaker diagnosis of atrial tachyarrhythmias and close correlation with actual AT documented by ambulatory monitoring.[7,13,15-19] Our findings are in agreement with the above observations with respect to the high positive predictive value of advanced pacemaker diagnostics (90.2%).
Asymptomatic AT has been reported to be up to 12 times more frequent than symptomatic AT, even in patients with a history of "symptomatic" AT.[20] Pacemaker diagnostics have recently enabled a closer look at this otherwise difficult to diagnose arrhythmia. High incidence of recurrent AT was documented in pacemaker recipients.[8,10] Recently, Israel et al.[10] demonstrated recurrent AF in 88% of patients by review of stored EGM and in 46% of patients by electrocardiogram (ECG) recordings during follow-up in a study of 110 patients with prior AF and Class I indications for pacing. These observations clearly indicate clinical utility of pacemaker diagnostics, particularly in view of the fact that 38% of AHRE in that study were completely asymptomatic. Another interesting finding was the nonspecific nature of AT symptoms. For example, 40% of patients in that study reported symptoms but did not have any documented arrhythmias. A similarly poor correlation between pacemaker diagnosed AHRE and symptoms was found by the AIDA trial investigators [7] and an earlier transtelephonic study.[5] Similar incidence of asymptomatic AT (31% during at least 2 follow-up visits) as detected by automatic analysis of pacemaker diagnostics in patients without prior AT history was reported by Schuchert et al.[21] Another interesting observation by Israel et al. was that freedom from AT for ≥3 months did not preclude arrhythmia recurrence.[10] Our findings expand these prior observations to patients without prior AT history and confirm that AT is a recurrent arrhythmia with non-normal pattern and a high incidence of asymptomatic episodes. Therapeutic implications of these findings may be extremely important should it be eventually proven that asymptomatic AT episodes are associated with a higher stroke risk or other co-morbidities. The present trial is one of the first to investigate the prevalence of AHRE in pacemaker recipients without prior documented AT. There was no difference in mortality between patients with and without history of AT suggesting that higher AT burden observed in the former group did not result in excess mortality. However, the trial was not powered to test the impact of AHRE on survival and major morbidity such as stroke. Decisions about the use of medications were left to the treating physician. Therefore, no conclusions regarding the influence of AHRE on mortality and morbidity can be drawn from our data and further studies are needed.
AT burden in this study was found to have a non-normal distribution and was therefore analyzed using nonparametric methods such as bootstrap analysis. This finding is in agreement with prior observations on distribution and clustering of AT events.[22] Future AF studies should take into account this non-normal occurrence of AHRE events and use appropriate nonparametric statistical tools for analysis.
The observed association between AT and advanced age is consistent with prior reports.[1,2,23] Also, our analysis shows that the presence of coronary artery disease (CAD) seemed to have a "protective" role, as the incidence of AHRE was actually lower in patients with versus without history of CAD. However, this seemingly paradoxical association was no longer observed when the data were controlled for beta-blocker use by performing separate analyses for patients with beta-blockers prescribed at baseline and patients without beta-blockers prescribed at baseline. These observations suggest the potential antiarrhythmic and cardio-protective benefits of beta-adrenergic antagonists in a high-risk population, as reported previously.[24]
We observed a higher incidence of AHRE that initiated as bradycardia (atrial rate < 80 bpm) in patients without prior AT history while the majority of AHRE started as tachycardia (ventricular rate > 80 bpm) in both groups. There was no difference in AHRE onset in patients who later developed persistent AT and those who did not. Prior studies have demonstrated that the onset patterns of paroxysmal and chronic AF differ in the cycle length (i.e. shorter in patients with persistent AF) and the degree of organization.[25,26] Circadian variation of the cycle length is also present. Kerr et al.[27] have observed higher ventricular response rates characterize patients who are less likely to progress to permanent AF. While the onset characteristics of AF episodes will require further studies, our observations indicate different subtypes of arrhythmia in patients with AF.
Limitations
The number of symptomatic episodes may have been underestimated in patients who experienced a large number of episodes between device interrogations since they could have exceeded the pacemaker memory capacity. This may have partially confounded the correlation between the symptoms and AHRE and the analysis of episodes onset characteristics. However, this is applicable only to a small number of patients in this study whose pacemaker memory capacity was exceeded and thus is unlikely to make a significant impact on the results. An additional analysis comparing symptoms to daily AT activity available in a subset of devices with larger memory capacity and consequently less likely to have the earlier AHRE overwritten by later episodes (Kappa 900) also indicated that most of the symptoms documented by patients were not accompanied by AHREs. Additionally, symptoms were recorded in the diary and not directly in the pacemaker memory allowing for only approximate correlation with AHRE if both occurred on the same day.
Conclusions
The A-HIRATE study demonstrated that atrial tachyarrhythmias are common in the general pacemaker population. Patients with prior history of AT show a higher arrhythmia burden, but the subsequent incidence is quite considerable even in those patients without any history of atrial arrhythmias. The majority of atrial tachyarrhythmias in this patient population are asymptomatic and symptoms do not correspond to an actual arrhythmic episode in most patients. The Atrial High Rate Diagnostic has a high positive predictive value for identifying AT events. The distribution of AT is non-normal and commands the use of nonparametric criteria for the assessment of arrhythmia burden.
Pacing Clin Electrophysiol. 2007;30(3):404-411. ©2007 Blackwell Publishing
Abstract
Background: The epidemiology and clinical implications of asymptomatic atrial tachyarrhythmias (AT) including both atrial fibrillation and flutter in pacemaker recipients with and without arrhythmia history are not well understood. The Atrial High Rate Episodes (A-HIRATE) in Pacemaker Patients Trial was designed to identify and compare the incidence of AT in patients with and without previously diagnosed AT and a standard indication for dual chamber pacing, and to provide useful diagnostic information for clinical management.
Methods: Four hundred twenty-seven patients were implanted with a pacemaker (Kappa 7-900, Medtronic, Inc., Minneapolis, MN, USA) capable of detecting and storing multiple atrial high rate episodes (AHRE) and followed for 2 years. Group I included 331 patients without prior history of AT and Group II included 96 patients with prior AT history.
Results: Pacemaker diagnostics appropriately detected 93% of reviewed AHRE. The rate of occurrence of first AHRE was significantly higher (P < 0.0001) in Group II patients, as was average AHRE burden. The rate of first AHRE occurrence was 88.6% for patients in Group II and 53.8% in Group I at 24 months post-implant. The rate of AHRE occurrence was similar in both groups after the first month post-implant. The majority of stored AHRE were asymptomatic; symptoms did not correspond to an actual AHRE in most patients.
Conclusions: The incidence of AT in pacemaker recipients is high. Most device-detected AHRE are asymptomatic. Prior history of AT is associated with higher arrhythmia burden. AHRE diagnostics have a high positive predictive value for identifying AT events.
Introduction
Atrial tachyarrhythmias (AT), including atrial fibrillation (AF) and flutter, occur frequently in the general population and are responsible for considerable morbidity and mortality, primarily related to stroke.[1-3] According to US Medicare data, the risk of one-year stroke occurrence more than doubled in patients with AT compared to those without AT.[3] AT also accounts for the majority of hospital admissions with arrhythmia as the primary diagnosis.[3,4] However, these reports are based primarily on symptomatic AF and thus allow correlation with subsequent complications. In contrast, the importance of more difficult to detect asymptomatic atrial arrhythmias was underestimated until recently[5,6] and its relevance to morbidity and mortality is less well known. Recently, the introduction of pacemakers with capacity to detect, quantify, and store asymptomatic AT episodes has resulted in new insights into minimally symptomatic AT.[7-10] The epidemiology and clinical implications of this arrhythmia have been studied in pacemaker recipients with prior history of AT.[10] However, despite these recent advances, the importance of asymptomatic AT in clinical practice remains less clear than that of symptomatic AT.
The purpose of the Atrial High Rate Episodes (A-HIRATE) in Pacemaker Patients Trial was to identify the incidence of AT in patients with previously undiagnosed AT and a standard indication for dual chamber pacing, and to provide useful diagnostic information for successful clinical management.
Methods
The A-HIRATE Trial was a multicenter, prospective study assessing the incidence of atrial high rate episodes (AHRE) in pacemaker patients with and without previously diagnosed AT. The trial was conducted in 44 centers in the US, Australia, and France. Each institutional review board approved the study protocol and each participant provided written informed consent. Patients were followed for two years including scheduled follow-up visits at 1, 6, 12, 18, and 24 months. The first patient was enrolled in July of 2000 and the trial was completed in August of 2004. The study consisted of two arms: Group I included patients without previously diagnosed AT and Group II consisted of patients with a prior history of AT as indicated by the enrolling center. Patients in both study arms were required to have an approved indication for pacemaker implantation.[11] The study aimed to determine the incidence of asymptomatic and symptomatic AT, arrhythmia onset characteristics, cumulative AT burden (i.e. cumulative AT episode duration), and to examine the accuracy of AHRE diagnostics. Dual chamber multiprogrammable pacemakers, (Kappa 700 or Kappa 900, Medtronic, Inc., Minneapolis, MN, USA) were implanted in all trial participants. No specific treatments or therapies were required.
Patients were required to program the Atrial High Rate Diagnostic and Clinician Selected Atrial High Rate Detail "ON." The Atrial High Rate Diagnostic records both AHRE summary information and specific episode information. The summary information includes AHRE counts, as well as the percentage of time during the collection period that an AHRE was detected (i.e. "burden"). Specific AHRE information in the Atrial High Rate Diagnostic includes the date, time, and duration of each episode for up to 16 episodes as follows: the Kappa 700 recorded data for the most recent 14 episodes plus the first, fastest, and longest episodes, while the Kappa 900 device recorded data from the most recent 13 episodes plus the first, fastest, and longest episodes. The Atrial High Rate Detail collected device marker channel and beat-to-beat data for up to eight atrial episodes, as well as daily activity recorded in the Atrial Arrhythmia Trend including data on pre-onset events, post-onset events, and pre-termination events. Kappa 900 devices also recorded the cumulative daily AHRE burden (hours/day) for up to 175 consecutive days.
Mode Switch was programmed ON with a 60-second delay in order to avoid detection of non-sustained AT episodes. Decreases in the recommended programmed mode switch delay were allowed in the event of symptomatic AT. An AHRE was defined via device programming as an atrial rate >180 bpm. The minimal episode duration for AHRE detection was programmed to 60 seconds since shorter episodes have questionable clinical significance and are also more likely to be inappropriately detected episodes.[12] Persistent AT was defined as at least seven consecutive days with device classified AHRE burden greater than 22 hours/day. Device programming parameters were recorded at the time of implant and at each follow-up visit. Stored device data including electrograms and the Atrial High Rate Diagnostic data were collected at each follow-up visit. AHRE burden was determined by the device as the cumulative duration of all AHRE divided by the follow-up period. Onset of stored AHRE was classified as bradycardia if the atrial rate was less than 80 bpm and classified as tachycardia if the rate was greater than 80 bpm. A subset of sequentially received device-stored episodes including atrial electrogram and marker channel were reviewed according to prospectively determined criteria in order to validate the accuracy of AHRE detection as previously described.[13]
Patients were issued symptom diaries to record AT symptoms including: "heart fluttering," "skipping," "racing," " light-headedness," "dizziness," "fainting," "chest pain/pressure or fullness," "shortness of breath," and "fatigue," respectively. A symptomatic event was defined as a device-detected AHRE occurring on the same day as patient-reported symptoms. The number of symptomatic episodes per patient-month was determined for each patient by dividing the number of symptomatic episodes for the patient by the total device-measured follow-up period.
Statistical Methods
Fisher's exact test was used to compare demographics between the two groups for qualitative measures, while a t-test was used to compare quantitative measures. Time to first device documented AHRE was compared via AT-free survival analysis by the Kaplan-Meier method for each AT arm. The one-year point estimate and corresponding 95% confidence interval were generated for each arm, and a Log rank test was performed to compare the rate of first occurrence or first recurrence between the two arms. A similar analysis was performed comparing time between a patient's first and second device-detected episodes between the two arms. For the analysis of AHRE burden, a bootstrap confidence interval[14] on the difference in mean burden between the two arms was applied because of the observed non-normal distribution of the burden data. A similar method was used in the analysis of symptomatic episodes. A bootstrap confidence interval on the difference in mean symptomatic episodes per patient month between the two arms was then calculated. Predictors of AHRE occurrence were determined using univariate analyses in the group without prior AT history. All quantitative demographic data are reported as mean ± SD unless indicated. A P-value <0.05 was considered significant.
Results
Recorded data from 427 of the 453 enrolled patients were analyzed, including 331 in the group without prior history of AT (Group I) and 96 patients in the prior AT history group (Group II). Twenty-six patients were excluded from the analysis cohort due to the presence of an ICD or active antiarrhythmic drug therapy at enrollment (Group I). The full 24-month follow-up period was completed by 312 of the patients. Demographic data for both groups are compared in Table 1 . The group with AT history included significantly more females than the primary arm. Patients with AT history had a higher prevalence of sinus node dysfunction, lower prevalence of atrioventricular (AV) block, and higher New York Heart Association (NYHA) Class. In patients with a history of AT, structural heart disease, as defined by coronary artery disease, was more common, while ejection fraction did not differ between groups. There were 32 deaths during the study follow-up period (approximately 7.3% in each group).
The hazard rate of first device-detected AHRE occurrence was significantly higher in patients with history of AT (Figure 1) compared to those without a history of diagnosed AT (P < 0.0001). At 12 and 24 months post-implant, the estimated Kaplan-Meier AHRE-free survival rates for patients with a history of AT were 22.6% and 11.4%, respectively. In the arm without prior AT history, a total of 159 out of 331 patients experienced at least one AHRE; the AHRE-free rates for this patient group were 59.2% and 46.2% at 12 and 24 months post-implant, respectively. Patients in the AT history group were also significantly more likely to experience a second AHRE reoccurrence. The 24-month survival free rate from device-detected AHRE was 42.1% (95% CI: 34.3-51.6%) for the 182 patients with no history of AT and a primary device indication of conduction block and 49.0% (95% CI: 40.3-59.5%) for the 119 patients with no AT history and sinus node dysfunction (P = 0.3). The 24-month AHRE survival rate for the remaining 30 patients with an indication other than SND or AV block was 56.6% (95% CI: 40.4-79.2%). AHRE burden throughout follow-up was significantly higher in the AT history group. The average burden over all follow-up in patients with no history of AT was 0.6 hours per day, compared to 4.4 hours per day among patients with a history of AT (Figure 2). A two-sided bias-corrected 95% bootstrap confidence interval on the average (AT history-no AT history) difference in AHRE burden over all follow-up was determined to be (2.23-5.55 hours per day). Since the interval does not contain 0, it was concluded that patients with AT history have greater AHRE burden than those without. Of the 156 patients in the analysis cohort with Kappa 900 devices, 25 met the prescribed criteria for persistent AT during follow-up, including 20 (26.3%) from the group with AT history and 5 (6.3%) in the group with no AT history.
Discussion
The principal findings of this study are as follows: the incidence of AT in pacemaker recipients is high, as 89% of patients with and 46% of patients without prior AT history experienced a sustained AHRE by 24 months. Prior history of AT is associated with higher arrhythmia burden, which has a non-normal distribution. Most device-detected AHRE are asymptomatic. Symptomatic AT episodes are more common in patients with prior AT but overall incidence of symptomatic AT is quite low. The positive predictive value of the Atrial High Rate Diagnostic is high.
The correlation between AHRE and actual AT events may have important clinical implications. Pollack et al[15] have demonstrated a high correlation (88%) between episodes classified by pacemaker as AHRE and intracardiac electrograms (EGMs). In the ancillary MOST analysis, an excellent correlation between AHRE and AT was provided by Holter monitoring, albeit in a small subset of patients.[16] Other studies have also demonstrated high sensitivity and specificity of pacemaker diagnosis of atrial tachyarrhythmias and close correlation with actual AT documented by ambulatory monitoring.[7,13,15-19] Our findings are in agreement with the above observations with respect to the high positive predictive value of advanced pacemaker diagnostics (90.2%).
Asymptomatic AT has been reported to be up to 12 times more frequent than symptomatic AT, even in patients with a history of "symptomatic" AT.[20] Pacemaker diagnostics have recently enabled a closer look at this otherwise difficult to diagnose arrhythmia. High incidence of recurrent AT was documented in pacemaker recipients.[8,10] Recently, Israel et al.[10] demonstrated recurrent AF in 88% of patients by review of stored EGM and in 46% of patients by electrocardiogram (ECG) recordings during follow-up in a study of 110 patients with prior AF and Class I indications for pacing. These observations clearly indicate clinical utility of pacemaker diagnostics, particularly in view of the fact that 38% of AHRE in that study were completely asymptomatic. Another interesting finding was the nonspecific nature of AT symptoms. For example, 40% of patients in that study reported symptoms but did not have any documented arrhythmias. A similarly poor correlation between pacemaker diagnosed AHRE and symptoms was found by the AIDA trial investigators [7] and an earlier transtelephonic study.[5] Similar incidence of asymptomatic AT (31% during at least 2 follow-up visits) as detected by automatic analysis of pacemaker diagnostics in patients without prior AT history was reported by Schuchert et al.[21] Another interesting observation by Israel et al. was that freedom from AT for ≥3 months did not preclude arrhythmia recurrence.[10] Our findings expand these prior observations to patients without prior AT history and confirm that AT is a recurrent arrhythmia with non-normal pattern and a high incidence of asymptomatic episodes. Therapeutic implications of these findings may be extremely important should it be eventually proven that asymptomatic AT episodes are associated with a higher stroke risk or other co-morbidities. The present trial is one of the first to investigate the prevalence of AHRE in pacemaker recipients without prior documented AT. There was no difference in mortality between patients with and without history of AT suggesting that higher AT burden observed in the former group did not result in excess mortality. However, the trial was not powered to test the impact of AHRE on survival and major morbidity such as stroke. Decisions about the use of medications were left to the treating physician. Therefore, no conclusions regarding the influence of AHRE on mortality and morbidity can be drawn from our data and further studies are needed.
AT burden in this study was found to have a non-normal distribution and was therefore analyzed using nonparametric methods such as bootstrap analysis. This finding is in agreement with prior observations on distribution and clustering of AT events.[22] Future AF studies should take into account this non-normal occurrence of AHRE events and use appropriate nonparametric statistical tools for analysis.
The observed association between AT and advanced age is consistent with prior reports.[1,2,23] Also, our analysis shows that the presence of coronary artery disease (CAD) seemed to have a "protective" role, as the incidence of AHRE was actually lower in patients with versus without history of CAD. However, this seemingly paradoxical association was no longer observed when the data were controlled for beta-blocker use by performing separate analyses for patients with beta-blockers prescribed at baseline and patients without beta-blockers prescribed at baseline. These observations suggest the potential antiarrhythmic and cardio-protective benefits of beta-adrenergic antagonists in a high-risk population, as reported previously.[24]
We observed a higher incidence of AHRE that initiated as bradycardia (atrial rate < 80 bpm) in patients without prior AT history while the majority of AHRE started as tachycardia (ventricular rate > 80 bpm) in both groups. There was no difference in AHRE onset in patients who later developed persistent AT and those who did not. Prior studies have demonstrated that the onset patterns of paroxysmal and chronic AF differ in the cycle length (i.e. shorter in patients with persistent AF) and the degree of organization.[25,26] Circadian variation of the cycle length is also present. Kerr et al.[27] have observed higher ventricular response rates characterize patients who are less likely to progress to permanent AF. While the onset characteristics of AF episodes will require further studies, our observations indicate different subtypes of arrhythmia in patients with AF.
Limitations
The number of symptomatic episodes may have been underestimated in patients who experienced a large number of episodes between device interrogations since they could have exceeded the pacemaker memory capacity. This may have partially confounded the correlation between the symptoms and AHRE and the analysis of episodes onset characteristics. However, this is applicable only to a small number of patients in this study whose pacemaker memory capacity was exceeded and thus is unlikely to make a significant impact on the results. An additional analysis comparing symptoms to daily AT activity available in a subset of devices with larger memory capacity and consequently less likely to have the earlier AHRE overwritten by later episodes (Kappa 900) also indicated that most of the symptoms documented by patients were not accompanied by AHREs. Additionally, symptoms were recorded in the diary and not directly in the pacemaker memory allowing for only approximate correlation with AHRE if both occurred on the same day.
Conclusions
The A-HIRATE study demonstrated that atrial tachyarrhythmias are common in the general pacemaker population. Patients with prior history of AT show a higher arrhythmia burden, but the subsequent incidence is quite considerable even in those patients without any history of atrial arrhythmias. The majority of atrial tachyarrhythmias in this patient population are asymptomatic and symptoms do not correspond to an actual arrhythmic episode in most patients. The Atrial High Rate Diagnostic has a high positive predictive value for identifying AT events. The distribution of AT is non-normal and commands the use of nonparametric criteria for the assessment of arrhythmia burden.
segunda-feira, 8 de setembro de 2008
Atrial Fibrillation in Stroke-Free Patients Is Associated With Memory Impairment and Hippocampal Atrophy
Author(s): Knecht S, Oelschlager C, Duning T, et al.
Citation: Eur Heart J 2008;Jul 29:[Epub ahead of print].
Clinical Trial: No
Study Question: Does atrial fibrillation (AF) cause cognitive impairment independent of stroke?
Methods: Detailed neuropsychological testing and brain magnetic resonance imaging (MRI) were performed in 112 patients with AF (mean age 60 years, paroxysmal AF in 54%) and 563 age-matched controls (mean age 64 years). Patients with prior stroke were excluded. In the AF group, 52% of patients were treated with warfarin and 23% with a platelet inhibitor. The association between AF and cognitive impairment was assessed by multivariate analysis that included other vascular risk factors such as hypertension, smoking, and diabetes.
Results: AF was independently associated with a small but statistically significant decrease in learning, memory, attention, and executive functions. There was no significant difference in cognitive scores between patients with paroxysmal and persistent AF. Hippocampal volume by MRI was approximately 8% smaller in patients with AF. AF was not associated with any change in total brain volume.
Conclusions: AF is associated with cognitive impairment and shrinkage of the hippocampus independent of stroke and other vascular risk factors.
Perspective: Shrinkage of the hippocampus, which is highly sensitive to vascular injury, provides a structural basis for the cognitive impairment associated with AF. Aside from stroke, AF is associated with microembolization, platelet dysfunction, and endothelial dysfunction, and one or more of these factors could account for injury to the hippocampus. The decreases in cognitive performance were relatively small in magnitude, raising some question as to whether the findings were clinically meaningful. Nevertheless, the results are noteworthy and suggest that AF may decrease cognitive reserve. This may explain why AF is associated with accelerated deterioration in patients with Alzheimer disease. Fred Morady, M.D., F.A.C.C.
Citation: Eur Heart J 2008;Jul 29:[Epub ahead of print].
Clinical Trial: No
Study Question: Does atrial fibrillation (AF) cause cognitive impairment independent of stroke?
Methods: Detailed neuropsychological testing and brain magnetic resonance imaging (MRI) were performed in 112 patients with AF (mean age 60 years, paroxysmal AF in 54%) and 563 age-matched controls (mean age 64 years). Patients with prior stroke were excluded. In the AF group, 52% of patients were treated with warfarin and 23% with a platelet inhibitor. The association between AF and cognitive impairment was assessed by multivariate analysis that included other vascular risk factors such as hypertension, smoking, and diabetes.
Results: AF was independently associated with a small but statistically significant decrease in learning, memory, attention, and executive functions. There was no significant difference in cognitive scores between patients with paroxysmal and persistent AF. Hippocampal volume by MRI was approximately 8% smaller in patients with AF. AF was not associated with any change in total brain volume.
Conclusions: AF is associated with cognitive impairment and shrinkage of the hippocampus independent of stroke and other vascular risk factors.
Perspective: Shrinkage of the hippocampus, which is highly sensitive to vascular injury, provides a structural basis for the cognitive impairment associated with AF. Aside from stroke, AF is associated with microembolization, platelet dysfunction, and endothelial dysfunction, and one or more of these factors could account for injury to the hippocampus. The decreases in cognitive performance were relatively small in magnitude, raising some question as to whether the findings were clinically meaningful. Nevertheless, the results are noteworthy and suggest that AF may decrease cognitive reserve. This may explain why AF is associated with accelerated deterioration in patients with Alzheimer disease. Fred Morady, M.D., F.A.C.C.
Permanent Atrial Fibrillation Affects Exercise Capacity in Chronic Heart Failure Patients
Title: Permanent Atrial Fibrillation Affects Exercise Capacity in Chronic Heart Failure Patients
Author(s): Agostoni P, Emdin M, Corra U, et al.
Citation: Eur Heart J 2008;Aug 5:[Epub ahead of print].
Clinical Trial: No
Study Question: Does atrial fibrillation (AF) have a negative impact on exercise tolerance in patients with heart failure (HF)?
Methods: This was a retrospective analysis of 942 patients with HF who underwent cardiopulmonary exercise testing (CPET). Patients were categorized by the presence (n = 180) or absence (n = 762) of permanent AF, defined as AF present continuously for >1 year.
Results: Peak heart rate was significantly higher in the AF group (136 vs. 125 bpm). Peak oxygen consumption (VO2) was significantly lower in the AF group (1024 vs. 1156 ml/min/kg), as were several other CPET parameters. When corrected for age, gender, and ejection fraction, AF still was associated with a lower peak VO2.
Conclusions: In patients with HF, AF significantly impairs exercise performance.
Perspective: There are three potential mechanisms by which AF negatively impacts cardiac performance: an excessive heart rate response to exercise, irregularity of the rhythm, and loss of atrioventricular synchrony. Therefore, it is not surprising that AF compromises exercise performance in patients with HF. A prior study demonstrated that restoration of sinus rhythm by radiofrequency catheter ablation in HF patients with AF resulted in a significant improvement in ejection fraction and decrease in left ventricular diameter, even in patients who had good rate control in AF. The present study, along with this prior study, provides support for a rhythm-control strategy in HF patients with AF. Fred Morady, M.D., F.A.C.C.
Author(s): Agostoni P, Emdin M, Corra U, et al.
Citation: Eur Heart J 2008;Aug 5:[Epub ahead of print].
Clinical Trial: No
Study Question: Does atrial fibrillation (AF) have a negative impact on exercise tolerance in patients with heart failure (HF)?
Methods: This was a retrospective analysis of 942 patients with HF who underwent cardiopulmonary exercise testing (CPET). Patients were categorized by the presence (n = 180) or absence (n = 762) of permanent AF, defined as AF present continuously for >1 year.
Results: Peak heart rate was significantly higher in the AF group (136 vs. 125 bpm). Peak oxygen consumption (VO2) was significantly lower in the AF group (1024 vs. 1156 ml/min/kg), as were several other CPET parameters. When corrected for age, gender, and ejection fraction, AF still was associated with a lower peak VO2.
Conclusions: In patients with HF, AF significantly impairs exercise performance.
Perspective: There are three potential mechanisms by which AF negatively impacts cardiac performance: an excessive heart rate response to exercise, irregularity of the rhythm, and loss of atrioventricular synchrony. Therefore, it is not surprising that AF compromises exercise performance in patients with HF. A prior study demonstrated that restoration of sinus rhythm by radiofrequency catheter ablation in HF patients with AF resulted in a significant improvement in ejection fraction and decrease in left ventricular diameter, even in patients who had good rate control in AF. The present study, along with this prior study, provides support for a rhythm-control strategy in HF patients with AF. Fred Morady, M.D., F.A.C.C.
No Benefit From Defibrillation Threshold Testing in the SCD-HeFT
Title: No Benefit From Defibrillation Threshold Testing in the SCD-HeFT (Sudden Cardiac Death in Heart Failure Trial)
Date Posted: 8/29/2008
Author(s): Blatt JA, Poole JE, Johnson GW, et al.
Citation: J Am Coll Cardiol 2008;52:551-556.
Clinical Trial: No Related Resources
Trial: locked content Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT)
Study Question: Does defibrillation threshold (DFT) testing have clinical value in patients with heart failure who receive an implantable cardioverter defibrillator (ICD) for 1° prevention of sudden death?
Methods: This was a post-hoc analysis of 717 patients in SCD-HeFT who underwent DFT testing at the time of ICD implantation. Ventricular fibrillation was induced with T-wave shocks. The first shock tested was 20 J and the second shock tested was 10 or 30 J, depending on whether the first shock was successful or unsuccessful. The ICDs were programmed with a first shock of 30 J if the DFT was >10 J or 20 J if the DFT was ≤10 J. Defibrillation efficacy of the first appropriate shock during follow-up was analyzed.
Results: The DFT was low (≤10 J) in 547 patients (76%) and high (>10 J) in 170 patients. Overall mortality was approximately 20%, with no difference between the low- and high-DFT groups. An appropriate shock occurred during follow-up in 22% of patients, and the first-shock efficacy was 83%, with no relationship between efficacy and DFT. The first-shock efficacy was 90% in 94 patients for whom no DFT data were available. Only 3 of 31 patients with an unsuccessful first shock died the same day.
Conclusions: There is no relationship between the results of DFT testing and shock efficacy or survival during follow-up.
Perspective: The results make a strong case for limited DFT testing in patients receiving an ICD for 1° prevention of sudden death. It is noteworthy that the DFT never was >30 J in this study, probably because of improvements in ICD technology. Fred Morady, M.D., F.A.C.C.
Date Posted: 8/29/2008
Author(s): Blatt JA, Poole JE, Johnson GW, et al.
Citation: J Am Coll Cardiol 2008;52:551-556.
Clinical Trial: No Related Resources
Trial: locked content Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT)
Study Question: Does defibrillation threshold (DFT) testing have clinical value in patients with heart failure who receive an implantable cardioverter defibrillator (ICD) for 1° prevention of sudden death?
Methods: This was a post-hoc analysis of 717 patients in SCD-HeFT who underwent DFT testing at the time of ICD implantation. Ventricular fibrillation was induced with T-wave shocks. The first shock tested was 20 J and the second shock tested was 10 or 30 J, depending on whether the first shock was successful or unsuccessful. The ICDs were programmed with a first shock of 30 J if the DFT was >10 J or 20 J if the DFT was ≤10 J. Defibrillation efficacy of the first appropriate shock during follow-up was analyzed.
Results: The DFT was low (≤10 J) in 547 patients (76%) and high (>10 J) in 170 patients. Overall mortality was approximately 20%, with no difference between the low- and high-DFT groups. An appropriate shock occurred during follow-up in 22% of patients, and the first-shock efficacy was 83%, with no relationship between efficacy and DFT. The first-shock efficacy was 90% in 94 patients for whom no DFT data were available. Only 3 of 31 patients with an unsuccessful first shock died the same day.
Conclusions: There is no relationship between the results of DFT testing and shock efficacy or survival during follow-up.
Perspective: The results make a strong case for limited DFT testing in patients receiving an ICD for 1° prevention of sudden death. It is noteworthy that the DFT never was >30 J in this study, probably because of improvements in ICD technology. Fred Morady, M.D., F.A.C.C.
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