Does change in device detected frequency of non-sustained or diverted episodes serve as a marker for inappropriate shock therapy? Analyses from the INTRINSIC RV and ALTITUDE-REDUCES Trials.

AIMS: Implantable cardioverter-defibrillators (ICDs) treat ventricular tachycardia or fibrillation but may also deliver unnecessary shocks. We sought to determine if the frequency of ICD-detected non-sustained or diverted (NSD) episodes increases before appropriate or inappropriate ICD shocks. METHODS AND RESULTS: We evaluated NSD episodes in the INTRINSIC RV Trial and their relationship to ICD shocks (appropriate and inappropriate). Time from NSD to shock was analysed. Results were validated by utilizing 1495 adjudicated ICD and cardiac resynchronization therapy-defibrillator shocks following NSD episodes collected through the LATITUDE remote monitoring system as part of the ALTITUDE-REDUCES Study. In INTRINSIC RV, 185 participants received 373 shocks; 148 had at least 1 NSD episode. Non-sustained or diverted frequency increased 24 h before the first shock for those receiving an inappropriate (P < 0.01) but not an appropriate shock (P = 0.17). Patients with NSD episodes within 24 h of a shock were significantly more likely to receive inappropriate therapy [odds ratio (OR) = 3.12, P < 0.01]. At the receiver operator curve determined optimal cutoff, an NSD episode within 14 min before shock strongly predicted inappropriate therapy (sensitivity 48%, specificity 91%; OR = 8.8, and P < 0.001). The 14 min cut-off evaluated on an independent dataset of 1495 shock episodes preceded by an NSD in the ALTITUDE-REDUCES Study confirmed these results (sensitivity = 47%, specificity = 85%, OR = 5.0, and P < 0.001). CONCLUSION: Device-detected NSD episodes increase before inappropriate but not appropriate shocks. Novel alerts or automated algorithms based on NSD episodes may reduce inappropriate shocks.

Survival after shock therapy in implantable cardioverter-defibrillator and cardiac resynchronization therapy-defibrillator recipients according to rhythm shocked. The ALTITUDE survival by rhythm study.

OBJECTIVES: This study sought to determine if the risk of mortality associated with inappropriate implantable cardioverter-defibrillator (ICD) shocks is due to the underlying arrhythmia or the shock itself. BACKGROUND: Shocks delivered from ICDs are associated with an increased risk of mortality. It is unknown if all patients who experience inappropriate ICD shocks have an increased risk of death. METHODS: We evaluated survival outcomes in patients with an ICD and a cardiac resynchronization therapy defibrillator enrolled in the LATITUDE remote monitoring system (Boston Scientific Corp., Natick, Massachusetts) through January 1, 2010. First shock episode rhythms from 3,809 patients who acutely survived the initial shock were adjudicated by 7 electrophysiologists. Patients with a shock were matched to patients without a shock (n = 3,630) by age at implant, implant year, sex, and device type. RESULTS: The mean age of the study group was 64 ± 13 years, and 78% were male. Compared with no shock, there was an increased rate of mortality in those who received their first shock for monomorphic ventricular tachycardia (hazard ratio [HR]: 1.65, p < 0.0001), ventricular fibrillation/polymorphic ventricular tachycardia (HR: 2.10, p < 0.0001), and atrial fibrillation/flutter (HR: 1.61, p = 0.003). In contrast, mortality after first shocks due to sinus tachycardia and supraventricular tachycardia (HR: 0.97, p = 0.86) and noise/artifact/oversensing (HR: 0.91, p = 0.76) was comparable to that in patients without a shock. CONCLUSIONS: Compared with no shock, those who received their first shock for ventricular rhythms and atrial fibrillation had an increased risk of death. There was no significant difference in survival after inappropriate shocks for sinus tachycardia or noise/artifact/oversensing. In this study, the adverse prognosis after first shock appears to be more related to the underlying arrhythmia than to an adverse effect from the shock itself.

Impact of shock energy and ventricular rhythm on the success of first shock therapy: the ALTITUDE first shock study.

BACKGROUND: The efficacy of shock in converting different ventricular tachyarrhythmias has not been well characterized in a large natural-practice setting. OBJECTIVE: To determine shock success rate by energy and ventricular rhythm in a large cohort of patients with implantable cardioverter-defibrillators. METHODS: Two thousand patients with 5279 shock episodes were randomly sampled for analysis from the LATITUDE remote monitoring system. Within an episode, the rhythm preceding therapy (shock or antitachycardia pacing [ATP]) was adjudicated. Patients who died after unsuccessful implantable cardioverter-defibrillator shocks did not transmit final remote monitoring data and were not included in the study. RESULTS: Of 3677 shock episodes for ventricular tachyarrhythmia, 2679 were treated with shock initially and were classified as monomorphic ventricular tachycardia ( n = 1544), polymorphic/monomorphic ventricular tachycardia (n = 371), or ventricular fibrillation (n = 764). The success rate after the first, second, and final shock averaged 90.3%, 96.4%, and 99.8%, respectively. After unsuccessful initial ATP (n = 998), the first, second, and final shock was successful in 84.8%, 92.9%, and 100% of the episodes. The success rate after the first or second shock was significantly lower after failed ATP compared to shock as first therapy (both P<.001). Among episodes treated initially with shock, the success rate for monomorphic ventricular tachycardia (89.2%) when treated with energy level ≤ 20 J was significantly higher than that for ventricular fibrillation (80.8%) (P = .04). The level of shock energy was a significant predictor of the success of the first shock (odds ratio 1.16; 95% confidence interval 1.03-1.30; P = .013). CONCLUSIONS: The success rate of first shock as first therapy is approximately 90%, but was lower after failed ATP. Programming a higher level of energy after ATP is suggested.

Depression but not seizure factors or quality of life predicts suicidality in epilepsy.

The objective of this study was to determine prevalence and predictive risk factors of suicidality in a large sample of epilepsy outpatients. We prospectively examined 193 consecutive adult epilepsy outpatients for depression, including suicidal ideation. Demographic and epilepsy factors, medication toxicity and health-related quality of life were also evaluated. The prevalence of suicidal ideation within the past two weeks was 11.9%. Although medication toxicity, health-related quality of life and BDI scores were each associated with suicidal ideation in the bivariate analyses, only the BDI remained significant in the logistic regression analysis. About one-fourth of the subjects with suicidal ideation had no significant symptoms of depression. Recent thoughts of suicide are a common occurrence in the outpatient epilepsy clinic setting, but these are not predicted by gender, age, seizure factors, medication toxicity or self-perceived quality of life. Although depression is associated with suicidal ideation, about one-fourth of the suicidal subjects were euthymic or only mildly depressed.

Noise, artifact, and oversensing related inappropriate ICD shock evaluation: ALTITUDE noise study.

BACKGROUND: Approximately 12-21% of implantable cardioverter defibrillator (ICD) patients receive inappropriate shocks. We sought to determine the incidence and causes of noise/artifact and oversensing (NAO) resulting in ICD shocks. METHODS: A random sample of 2,000 patients who received ICD and cardiac resynchronization therapy defibrillator shocks and were followed by a remote monitoring system was included. Seven electrophysiologists analyzed stored electrograms from the 5,279 shock episodes. Episodes were adjudicated as appropriate or inappropriate shocks. RESULTS: Of the 5,248 shock episodes with complete adjudication, 1,570 (30%) were judged to be inappropriate shocks. Of these 1,570, 134 (8.5%) were a result of NAO. The 134 NAO episodes were determined to be due to external noise in 76 (57%), lead connector-related in 37 (28%), muscle noise in 11 (8%), oversensing of atrium in seven (5%), T-wave oversensing in two (2%), and other noise in one (1%). The ICD shock itself resulted in a marked decrease in the level of noise in 60 of 134 (45%) NAO episodes, and the magnitude of this effect varied with the type of NAO (58% for external noise, 35% for muscle, 27% for lead/connector, and 0% for oversensing; P = 0.03). There was no significant difference in NAO likelihood based on type of lead (integrated bipolar 89/1,802 vs dedicated bipolar 9/140, P = 0.67). CONCLUSIONS: External noise and lead/connector noise were the primary causes, while T-wave oversensing was the least common cause of NAO resulting in ICD shock. Noise/artifact decreased immediately after a shock in nearly half of episodes. The specific ICD lead type did not impact the likelihood of NAO.

Cardiac resynchronization therapy and the relationship of percent biventricular pacing to symptoms and survival.

BACKGROUND: With the advent of cardiac resynchronization therapy, it was unclear what percentage of biventricular pacing would be required to obtain maximal symptomatic and mortality benefit from the therapy. The optimal percentage of biventricular pacing and the association between the amount of continuous pacing and survival is unknown. OBJECTIVE: The purpose of this study was to assess the optimal percentage of biventricular pacing and any association with survival in a large cohort of networked patients. METHODS: A large cohort of 36,935 patients followed up in a remote-monitoring network, the LATITUDE Patient Management system (Boston Scientific Corp., Natick, Massachusetts), was assessed to determine the association between the percentage of biventricular pacing and mortality. RESULTS: The greatest magnitude of reduction in mortality was observed with a biventricular pacing achieved in excess of 98% of all ventricular beats. Atrial fibrillation and native atrial ventricular condition can limit a high degree of biventricular pacing. Incremental increases in mortality benefit are observed with an increasing percentage of biventricular pacing. CONCLUSION: Every effort should be made to reduce native atrioventricular conduction with cardiac resynchronization therapy systems in an attempt to achieve biventricular pacing as close to 100% as possible.

Real world evaluation of dual-zone ICD and CRT-D programming compared to single-zone programming: the ALTITUDE REDUCES study.

INTRODUCTION: We evaluated the frequency of appropriate and inappropriate shocks and survival in patients using dual-zone programming versus single-zone programming. METHODS AND RESULTS: For the ALTITUDE REDUCES study, patients were followed for 1.6 ± 1.1 years. The 12-month incidence of any shock was lower for dual-versus single-zone programmed detection at rates ≤170 bpm and between 170-200 bpm (P < 0.001). Appropriate shock rates at 1 year were also lower with dual-zone programming in these rate intervals (single zone 9.1%, 5.4%, P < 0.001, dual zone 6.7%, 4.7%, P < 0.02). There were no detectable differences between single- and dual-zone shock incidence at detection rates ≥ 200 bpm (P = 0.14). Inappropriate shock incidence was less with dual- versus single-zone detection at all detect rates <200 bpm, but not at rates ≥200 bpm (P < 0.001, P = 0.37). The lowest risk of appropriate and inappropriate shock was associated with dual-zone programming and detection rates ≥200 bpm (2.1%). Dual-zone detection was associated with more nonsustained and diverted therapy episodes but these patients did not have an increased risk of death compared to patients with single-zone programming. Patients programmed to low detection rate, single-zone detection and shock-only therapy also had the highest preshock mortality risk (P = 0.05). CONCLUSIONS: Shock incidence is lowest with either single- or dual-zone detection ≥200 bpm. For detection rates <200 bpm, dual-zone programming is associated with a reduction in the incidence of total shocks, appropriate shocks, and inappropriate shocks.

Implantable cardioverter defibrillator electrogram adjudication for device registries: methodology and observations from ALTITUDE.

BACKGROUND: The increasing use of remote monitoring with the associated large retrievable databases provides a unique opportunity to analyze observations on implantable cardioverter-defibrillator (ICD) therapies. Adjudication of a large number of stored ICD electrograms (EGMs) presents a unique challenge. The ALTITUDE study group was designed to use the LATITUDE remote monitoring system to evaluate ICD patient outcomes across the United States. METHODS AND RESULTS: Of 81,081 patients on remote monitoring, a random sample of 2,000 patients having 5,279 shock episodes was selected. The ALTITUDE EGM review committee was comprised of seven electrophysiologists from four institutions. An online EGM adjudication system was designed. Episodes were classified as appropriate (70% of shock episodes) or inappropriate ICD therapies (30%). Light's Kappa was used to assess agreement. Interobserver and intraobserver Kappa scores for dual-chamber ICDs were 0.84 (0.71-0.91) and 0.89 (0.82-0.95), consistent with substantial agreement. Interobserver and intraobserver Kappa scores for single-chamber ICDs were 0.61 (0.54-0.67) and 0.69 (0.59-0.79). The rhythm categories of "nonsustained arrhythmia" and "polymorphic and monomorphic ventricular tachycardia" resulted in the greatest degree of discordant adjudication between reviewers. CONCLUSIONS: This method of adjudication of a large volume of stored EGM data prior to device therapies will allow new observations in regards to device performance and has the potential to improve device programming and design. There was substantial interreviewer agreement for rhythm classification. Agreement was greater for dual-chamber compared to single-chamber devices, indicating the atrial lead adds diagnostic value in rhythm interpretation.

Adverse antiepileptic drug effects in new-onset seizures: a case-control study.

OBJECTIVE: Adverse effects (AEs) are a major concern when starting antiepileptic drug (AED) treatment. This study quantified the extent to which AE reporting in people with new-onset seizures started on AEDs is attributable to the medication per se, and investigated variables contributing to AE reporting. METHODS: We pooled data from 2 large prospective studies, the Multicenter Study of Early Epilepsy and Single Seizures and the Northern Manhattan Study of incident unprovoked seizures, and compared adverse event profile (AEP) total and factor scores between adult cases prescribed AEDs for new-onset seizures and untreated controls, adjusting for several demographic and clinical variables. Differences in AEP scores were also tested across different AED monotherapies and controls, and between cases and controls grouped by number of seizures. RESULTS: A total of 212 cases and 206 controls were identified. Most cases (94.2%) were taking low AED doses. AEP scores did not differ significantly between the 2 groups. Depression, female gender, symptomatic etiology, younger seizure onset age, ≥2 seizures, and history of febrile seizures were associated with higher AEP scores. There were no significant differences in AEP scores across different monotherapies and controls. AEP scores increased in both cases and controls with increasing number of seizures, the increment being more pronounced in cases. CONCLUSIONS: When AED treatment is started at low doses following new-onset seizures, AE reporting does not differ from untreated individuals. Targeting specific factors affecting AE reporting could lead to improved tolerability of epilepsy treatment.

Design and rationale of the assessment of proper physiologic response with rate adaptive pacing driven by minute ventilation or accelerometer (APPROPRIATE) trial.

Rate-adaptive sensors are designed to restore a physiologic heart rate response to activity, in particular for patients that have chronotropic incompetence (CI). Limited data exist comparing two primary types of sensors; an accelerometer (XL) sensor which detects activity or motion and a minute ventilation (MV) sensor, which detects the product of respiration rate and tidal volume. The APPROPRIATE study will evaluate the MV sensor compared with the XL sensor for superiority in improving functional capacity (peak VO(2)) in pacemaker patients that have CI. This study is a double-blind, randomized, two-arm trial that will enroll approximately 1,000 pacemaker patients. Patients will complete a 6-min walk test at the 2-week visit to screen for potential CI. Those projected to have CI will advance to a 1-month visit. At the 1-month visit, final determination of CI will be done by completing a peak exercise treadmill test while the pacemaker is programmed to DDDR with the device sensors set to passive. Patients failing to meet the study criteria for CI will not continue further in the trial. Patients that demonstrate CI will be randomized to program their rate-adaptive sensors to either MV or XL in a 1:1 ratio. The rate-adaptive sensor will be optimized for each patient using a short walk to determine the appropriate response factor. At a 2-month visit, patients will complete a CPX test with the rate-adaptive sensors in their randomized setting.

Long-term outcome after ICD and CRT implantation and influence of remote device follow-up: the ALTITUDE survival study.

BACKGROUND: Outcome data for patients receiving implantable cardioverter-defibrillator (ICD) and cardiac resynchronization therapy-defibrillator (CRT-D) devices treated outside of clinical trials are lacking. No clinical trial has evaluated mortality after device implantation or after shock therapy in large numbers of patients with implanted devices that regularly transmit device data over a network. METHODS AND RESULTS: Survival status in patients implanted with ICD and CRT devices across the United States from a single manufacturer was assessed. Outcomes were compared between patients followed in device clinic settings and those who regularly transmit remote data collected from the device an average of 4 times monthly. Shock delivery and electrogram analysis could be ascertained from patients followed on the network, enabling survival after ICD shock to be evaluated. One- and 5-year survival rates in 185,778 patients after ICD implantation were 92% and 68% and were 88% and 54% for CRT-D device recipients. In 8228 patients implanted with CRT-only devices, survival was 82% and 48% at 1 and 5 years, respectively. For the 69,556 ICD and CRT-D patients receiving remote follow-up on the network, 1- and 5-year survival rates were higher compared with those in the 116,222 patients who received device follow-up in device clinics only (50% reduction; P<0.0001). There were no differences between patients followed on or off the remote network for the characteristics of age, gender, implanted device year or type, and economic or educational status. Shock therapy was associated with subsequent mortality risk for both ICD and CRT-D recipients. CONCLUSIONS: Survival after ICD and CRT-D implantation in patients treated in naturalistic practice compares favorably with survival rates observed in clinical trials. Remote follow-up of device data is associated with excellent survival, but arrhythmias that result in device therapy in this population are associated with a higher mortality risk compared with patients who do not require shock therapy.

Global assessment of nitrogen deposition effects on terrestrial plant diversity: a synthesis.

Atmospheric nitrogen (N) deposition is a recognized threat to plant diversity in temperate and northern parts of Europe and North America. This paper assesses evidence from field experiments for N deposition effects and thresholds for terrestrial plant diversity protection across a latitudinal range of main categories of ecosystems, from arctic and boreal systems to tropical forests. Current thinking on the mechanisms of N deposition effects on plant diversity, the global distribution of G200 ecoregions, and current and future (2030) estimates of atmospheric N-deposition rates are then used to identify the risks to plant diversity in all major ecosystem types now and in the future. This synthesis paper clearly shows that N accumulation is the main driver of changes to species composition across the whole range of different ecosystem types by driving the competitive interactions that lead to composition change and/or making conditions unfavorable for some species. Other effects such as direct toxicity of nitrogen gases and aerosols, long-term negative effects of increased ammonium and ammonia availability, soil-mediated effects of acidification, and secondary stress and disturbance are more ecosystem- and site-specific and often play a supporting role. N deposition effects in mediterranean ecosystems have now been identified, leading to a first estimate of an effect threshold. Importantly, ecosystems thought of as not N limited, such as tropical and subtropical systems, may be more vulnerable in the regeneration phase, in situations where heterogeneity in N availability is reduced by atmospheric N deposition, on sandy soils, or in montane areas. Critical loads are effect thresholds for N deposition, and the critical load concept has helped European governments make progress toward reducing N loads on sensitive ecosystems. More needs to be done in Europe and North America, especially for the more sensitive ecosystem types, including several ecosystems of high conservation importance. The results of this assessment show that the vulnerable regions outside Europe and North America which have not received enough attention are ecoregions in eastern and southern Asia (China, India), an important part of the mediterranean ecoregion (California, southern Europe), and in the coming decades several subtropical and tropical parts of Latin America and Africa. Reductions in plant diversity by increased atmospheric N deposition may be more widespread than first thought, and more targeted studies are required in low background areas, especially in the G200 ecoregions.

Predictors of early mortality in implantable cardioverter-defibrillator recipients.

AIMS: Multiple trials have shown that implantable cardioverter defibrillators (ICDs) prolong survival in secondary and primary prevention populations. However, in spite of the efficacy of these devices in terminating life-threatening arrhythmias, total mortality remains high. METHODS AND RESULTS: We evaluated 1703 patients (mean age: 67 +/- 12 years, 82% male) with conventional ICD indications, who were enrolled and followed between 2001 and 2004 at 128 US centres. Patients were followed for up to a year, and vital status was obtained for 1655 patients (97%, median follow-up: 377 days). There were 183 deaths within 1 year of ICD implantation (1-year mortality rate: 16%). Predictors of mortality included a history of atrial fibrillation (AF, P < 0.0001), diabetes (P = 0.0001), failure to use cholesterol-lowering medications (P < 0.001), use of digitalis and derivatives (P < 0.0001), use of diuretics (P < 0.0001), low body mass index (BMI, P < 0.0001), increasing age (P < 0.0001), low left ventricular ejection fraction (P < 0.0001), low activity hours (P < 0.0001), elevated resting heart rate (P = 0.014), low mean arterial pressure (MAP, P = 0.007), and poor functional status (New York Heart Association class, P < 0.0001). In multivariate modelling, AF (P < or = 0.001), diabetes (P = 0.004), BMI (P = 0.001), MAP (P = 0.040), and functional class (P = 0.006) predicted mortality. CONCLUSION: In this population undergoing ICD implantation, poor functional status, low MAP, diabetes, low BMI, and AF were strongly associated with death within a year.

Comorbidity between temporal lobe epilepsy and depression: a [18F]MPPF PET study.

Brain and brainstem changes of serotoninergic 5-hydroxytryptophan (5-HT)(1A) receptor density have been reported in patients with major depressive disorder as well as in patients with temporal lobe epilepsy (TLE), using PET and the selective antagonist radiotracers [(11)C]WAY-100635 or [(18)F]FC-WAY. We used a distinct 5-HT(1A) antagonist, [(18)F]MPPF, whose binding potential depends on both receptor density and extracellular serotonin concentration, in 24 patients with drug-resistant TLE and MRI evidence of hippocampal sclerosis but without prior antidepressant exposure. Their Beck Depression Inventory (BDI-2) score ranged from 0 to 34, with nine patients having a score >11. We used a simplified reference tissue model, statistical parametric mapping and anatomical regions of interest (ROIs) to correlate parametric images of [(18)F]MPPF BP with the total BDI score and its four subclasses. The total BDI score, as well as symptoms of psychomotor anhedonia and negative cognition, correlated positively with [(18)F]MPPF BP in the raphe nuclei and in the insula contralateral to seizure onset, whereas somatic symptoms correlated positively with [(18)F]MPPF binding potential in the hippocampal/parahippocampal region ipsilateral to seizure onset, the left mid-cingulate gyrus and the inferior dorsolateral frontal cortex, bilaterally. We confirm an association of depressive symptoms in TLE patients with changes of the central serotoninergic pathways, in particular within the raphe nuclei, insula, cingulate gyrus and epileptogenic hippocampus. These changes are likely to reflect lower extracellular serotonin concentration in more depressed patients, with an upregulation of receptors a less likely alternative.

Frequency, duration, and predictors of newly-diagnosed atrial fibrillation following dual-chamber pacemaker implantation in patients without a previous history of atrial fibrillation.

The Silent Atrial Fibrillation Detection With Stored EGMs (SAFE) registry is the first prospective study to characterize the incidence, duration, and predictors of atrial high-rate episodes (AHREs) in patients without previous clinically diagnosed atrial fibrillation after dual-chamber pacemaker implantation. Patients underwent in-clinic device interrogation at 2 weeks and then 3, 6, and 12 months after implantation. An AHRE was defined as an atrial tachyarrhythmia with an atrial rate > or =180 beats/min lasting > or =5 minutes. During the first month after pacemaker implantation, AHREs were identified in 68 patients (4.6%). Thirty-four of these patients (50%) did not have AHREs beyond the first month after implantation; these patients were older than those who continued to have AHREs (79 +/- 9 vs 74 +/- 12 years, p = 0.05). Within the first 6 months after pacemaker implantation, 150 patients (10%) experienced a total of 455 AHREs, of which only 28 (6%) prompted clinical visits. The 6-month freedom from an AHRE was 82%. Overall, 75% of patients with AHREs had multiple episodes; most AHREs lasted 5 to 60 minutes. In conclusion, 6 months after dual-chamber pacemaker implantation, 10% of patients experienced > or =1 AHRE, usually lasting 5 to 60 minutes. Some patients had AHREs only within the first 30 days after implantation, suggesting the possibility of transient atrial proarrhythmia related to lead insertion.

Racial disparity in the utilization of implantable-cardioverter defibrillators among patients with prior myocardial infarction and an ejection fraction of

Age-adjusted sudden cardiac death rates are highest for black patients compared with other racial groups. The prophylactic implantation of an implantable cardioverter-defibrillator (ICD) provides a significant reduction in sudden cardiac death and overall mortality in patients after myocardial infarctions with significant left ventricular systolic dysfunction. The purpose of this study was to determine whether black patients with left ventricular systolic dysfunction were less likely than white patients to receive ICDs for the primary prevention of sudden cardiac death. Data from the National Registry to Advance Heart Health (ADVANCENT) were analyzed to determine which patients with histories of myocardial infarctions and ejection fractions

Prognostic value of heart rate variability footprint and standard deviation of average 5-minute intrinsic R-R intervals for mortality in cardiac resynchronization therapy patients.

BACKGROUND: Cardiac resynchronization therapy devices provide effective therapy for heart failure. Heart rate variability (HRV) parameters in the device such as HRV footprint and SD of average 5-minute intrinsic R-R intervals (SDANN) are related to autonomic function and may be used to identify patients with a higher risk of mortality. METHODS: We examined the relationship between HRV and mortality in a prospective cohort study. The 842 patients (mean age, 67.7 +/- 11.2; 23.5 % female; New York Heart Association class III, 88.6%; class IV, 11.4%) included in the analysis were implanted with a cardiac resynchronization therapy with defibrillation device and had baseline HRV measurements available. RESULTS: During a median of 11.6 months of follow-up, 7.8% (66/842) of patients died. Heart rate variability footprint and SDANN were significant predictors of mortality (all P < .05); patients with lower HRV values were at greater risk for death, compared with patients with higher HRV values. Heart rate variability changes over time tended to predict the risk of mortality in follow-up (P = nonsignificant); patients with low baseline HRV and small changes in HRV during the follow-up period were at the highest risk for death (7% mortality for SDANN and 8.9% for HRV footprint), and patients with high baseline HRV and large changes in HRV were at the lowest risk (1.5% mortality for SDANN and 2.4% for HRV footprint). Results were consistent when adjusted for age, sex, body mass index, and diastolic blood pressure. CONCLUSIONS: Continuously measured device HRV parameters provide prognostic information about patient mortality that may be helpful for risk stratification.

Cortical abnormalities in epilepsy revealed by local EEG synchrony.

Abnormally strong functional linkage between cortical areas has been postulated to play a role in the pathogenesis of partial epilepsy. We explore the possibility that such linkages may be manifest in the interictal EEG apart from epileptiform disturbances or visually evident focal abnormalities. We analyzed samples of interictal intracranial EEG (ICEEG) recorded from subdural grids in nine patients with medically intractable partial epilepsy, measuring interelectrode synchrony using the mean phase coherence algorithm. This analysis revealed areas of elevated local synchrony, or "hypersynchrony" which had persistent spatiotemporal characteristics that were unique to each patient. Measuring local synchrony in a subdural grid results in a map of the cortical surface that provides information not visually apparent on either EEG or structural imaging. We explore the relationship of hypersynchronous areas to the clinical evidence of seizure localization in each case, and speculate that local hypersynchrony may be a marker of epileptogenic cortex, and may prove to be a valuable aid to clinical ICEEG interpretation.

Hippocampal 1H-MRSI correlates with severity of depression symptoms in temporal lobe epilepsy.

OBJECTIVE: To investigate the association of an indicator of hippocampal function with severity of depression symptoms in temporal lobe epilepsy. METHODS: We evaluated 31 patients with video/EEG-confirmed temporal lobe epilepsy using creatine/N-acetylaspartate ratio maps derived from a previously validated (1)H magnetic resonance spectroscopic imaging ((1)H-MRSI) technique at 4.1 T. We also assessed depression symptoms, epilepsy-related factors, and self-perceived social and vocational disability. We used conservative nonparametric bivariate procedures to determine the correlation of severity of depression symptoms with imaging and clinical variables. RESULTS: The extent of hippocampal (1)H-MRSI abnormalities correlated with severity of depression (Spearman rho = 0.65, p value < 0.001), but other clinical factors did not. CONCLUSION: The extent of hippocampal dysfunction is associated with depression symptoms in temporal lobe epilepsy and may be a more important factor than seizure frequency or degree of disability.

Changes in heart rate variability, quality of life, and activity in cardiac resynchronization therapy patients: results of the HF-HRV registry.

BACKGROUND: Cardiac resynchronization therapy (CRT) is a viable therapy in the treatment of heart failure (HF). Heart rate variability (HRV) is a prognostic marker of HF and mortality and is a sign of autonomic dysfunction. Acute improvements in measures of HRV have been demonstrated after CRT in small clinical studies. The purpose of the present study was to evaluate changes in HRV and patient outcomes over time and the relationship between these changes in a large generalized sample of patients who received CRT with defibrillator (CRT-D). METHODS: The Heart Failure-Heart Rate Variability (HF-HRV) registry enrolled 1,421 patients who received a CRT-D device capable of measuring HRV. Patients were followed for a 1-year period. Device diagnostics, including HRV footprint; standard deviation of averaged normal R to R intervals (SDANN); and mean, minimum, and maximum heart rate were measured at each visit, in addition to activity log, New York Heart Association (NYHA) class, and quality of life (QOL) data. RESULTS: This large sample of HF patients showed an overall improvement in SDANN (69.2 +/- 25.5, 78.5 +/- 27.8, 79.4 +/- 27.2, 80.7 +/- 28.2) and HRV footprint (31.5 +/- 11.8, 33.4 +/- 12.3, 34.2 +/- 12.2, 34.5 +/- 12.3) at the 2 week, 3 month, 6 month, and 12 month visits, respectively (both P < 0.001). There were also significant changes over time in clinical status (improved QOL, increased activity, and improved NYHA, all P < 0.0001), with the greatest changes occurring between the 2 week and 3 month visits. CONCLUSION: In conclusion, these study results demonstrate that device measured HRV parameters and patient outcomes significantly improve after receipt of CRT.