Innovative solutions for disease management.

The increasing prevalence of chronic diseases is a driver for emerging big data technologies for healthcare including digital platforms for data collection, systems for active patient engagement and education, therapy specific predictive models, optimized patient pathway models. Powerful bioelectronic medicine tools for data collection, analysis and visualization allow for joint processing of large volumes of heterogeneous data, which in turn can produce new insights about patient outcomes and alternative interpretations of clinical patterns that can lead to implementation of optimized clinical decisions and clinical patient pathway by healthcare professionals.With this perspective, we identify innovative solutions for disease management and evaluate their impact on patients, payers and society, by analyzing their impact in terms of clinical outcomes (effectiveness, safety, and quality of life) and economic outcomes (cost-effectiveness, savings, and productivity).As a result, we propose a new approach based on the main pillars of innovation in the disease management area, i.e. progressive patient care models, patient-centric approaches, bioelectronics for precise medicine, and lean management that, combined with an increase in appropriate private-public-citizen-partnership, leads towards Patient-Centric Healthcare.

Short-spaced dipole for managing phrenic nerve stimulation in patients with CRT: the "phrenic nerve mapping and stimulation EP" catheter study.

BACKGROUND: Phrenic nerve stimulation (PNS), occurring in 33%-37% of the patients with cardiac resynchronization therapy (CRT), is a limiting factor when implanting left ventricular (LV) leads from coronary veins. OBJECTIVE: To test the hypothesis that PNS occurrence is related to bipolar electrode spacing. METHODS: During standard CRT defibrillator implant procedures, a 5-F diagnostic electrophysiology catheter with 10 electrodes, spaced 2-5-2 mm, was positioned in a cardiac vein suitable for permanent LV lead placement. Pacing in the unipolar configuration identified the site with the lowest PNS threshold. PNS and left ventricular pacing (LVP) thresholds were then measured in different configurations at 0.5 ms: unipolar, each LV electrode served as the cathode in turn; and bipolar with different electrode spacing, cathode being the electrode with the lowest unipolar PNS threshold. RESULTS: From February to September 2010, 40 patients undergoing CRT implantation were enrolled in 4 centers in Italy. It was possible to identify PNS and perform a complete set of measurements in 23 patients. A bipolar electrode spacing of 2 mm resulted in higher PNS thresholds in bipolar configurations han did a bipolar electrode spacing of ≥ 5 mm. However, no significant increase in the LVP threshold was observed (P = ns). CONCLUSIONS: This experience suggests that LVP with a bipolar electrode spacing of 2 mm significantly increases the PNS threshold without affecting the LVP threshold, thereby increasing the possibility of delivering CRT when the LV lead is placed in proximity to the phrenic nerve.

Effect of bipolar electrode spacing on phrenic nerve stimulation and left ventricular pacing thresholds: an acute canine study.

BACKGROUND: Phrenic nerve stimulation (PNS) is a common complication of cardiac resynchronization therapy when left ventricular (LV) pacing occurs via a coronary vein. The purpose of this study was to evaluate the effects of bipolar electrode spacing on PNS and LV pacing thresholds. METHODS AND RESULTS: Electrophysiology catheters with standard (2 mm-5 mm-2 mm) or modified (1 mm-5 mm-1 mm) interelectrode spacing was, respectively, inserted in a posterior/lateral cardiac vein in a randomized order in 6 anesthetized dogs via jugular access. The phrenic nerve was dissected via a left minithoracotomy and repositioned over the vein as close as possible to one of the electrodes. The presence of PNS was verified (ie, PNS threshold <2 V at 0.5 ms in unipolar configuration). Bipolar pacing was delivered using the electrode closest to the phrenic nerve as the cathode, and multiple bipolar electrode spacing configurations were tested. During bipolar pacing, PNS threshold increased as bipolar electrode spacing was reduced (P<0.05), whereas LV pacing thresholds did not change significantly (P>0.05). Compared with a standard bipolar electrode spacing of 20 mm for LV leads, 1 and 2 mm bipolar electrode spacing resulted in a PNS threshold increase of 5.5±2.2 V (P=0.003) and 2.8±1.7 V (P<0.001), respectively. Similarly, PNS threshold increased by 6.5±3.7 V with 1 mm and by 3.8±1.9 V with 2 mm bipolar pacing (both P<0.001), compared with unipolar pacing. CONCLUSIONS: This study suggests that reducing LV bipolar electrode spacing from the standard 20 mm to 1 or 2 mm may significantly increase the PNS threshold without compromising LV pacing thresholds.

Impact of mitral regurgitation on the outcome of patients treated with CRT-D: data from the InSync ICD Italian Registry.

BACKGROUND: We assessed the influence of clinically significant mitral regurgitation (MR) on clinical-echocardiographic response and outcome in heart failure (HF) patients treated with a biventricular defibrillator (cardiac resynchronization therapy defibrillator [CRT-D]). METHODS AND RESULTS: A total of 659 HF patients underwent successful implantation of CRT-D and were enrolled in a multicenter prospective registry (median follow-up of 15 months). Following baseline echocardiographic evaluation, patients were stratified into two groups according to the severity of MR: 232 patients with more than mild MR (Group MR+: grade 2, 3, and 4 MR) versus 427 patients with mild (grade 1) or no functional MR (Group MR-). On 6- and 12-month echocardiographic evaluation, MR was seen to have improved in the vast majority of MR+ patients, while it remained unchanged in most MR- patients. On 12-month follow-up evaluation, a comparable response to CRT was observed in the two groups, in terms of the extent of left ventricular reverse remodeling and combined clinical and echocardiographic response. During long-term follow-up, event-free survival did not differ between MR+ and MR- patients, even when subpopulations of patients with ischemic heart disease and with dilated cardiomyopathy were analyzed separately. On multivariate analysis, the only independent predictor of death from any cause was the lack of ß-blocker use. CONCLUSIONS: This observational analysis supports the use of CRT-D in HF patients with clinically significant MR; MR had no major influence on patient outcome.

Application of the Seattle Heart Failure Model in patients on cardiac resynchronization therapy.

BACKGROUND: The Seattle Heart Failure Model (SHFM) is a multimarker risk assessment tool able to predict outcome in heart failure (HF) patients. AIM: To assess whether the SHFM can be used to risk-stratify HF patients who underwent cardiac resynchronization therapy with (CRT-D) or without (CRT) an implantable defibrillator. METHODS AND RESULTS: The SHFM was applied to 342 New York Heart Association class III-IV patients who received a CRT (23%) or CRT-D (77%) device. Discrimination and calibration of SHFM were evaluated through c-statistics and Hosmer-Lemeshow (H-L) goodness-of-fit test. Primary endpoint was a composite of death from any cause/cardiac transplantation. During a median follow-up of 24 months (25th-75th percentile [pct]: 12-37 months), 78 of 342 (22.8%) patients died; seven patients underwent urgent transplantation. Median SHFM score for patients with endpoint was 5.8 years (25th-75th pct: 4.25-8.7 years) versus 8.9 years (25th-75th pct: 6.6-11.8 years) for those without (P < 0.001). Discrimination of SHFM was adequate for the endpoint (c-statistic always ranged around 0.7). The SHFM was a good fit of death from any cause/cardiac transplantation, without significant differences between observed and SHFM-predicted survival. CONCLUSION: The SHFM successfully stratifies HF patients on CRT/CRT-D and can be reliably applied to help clinicians in predicting survival in this clinical setting.

On-pump versus off-pump coronary artery bypass surgery in high-risk patients: operative results of a prospective randomized trial (on-off study).

OBJECTIVE: To analyze the risk reduction of cardiopulmonary bypass complications between on-pump and off-pump coronary artery bypass grafting in high-risk patients. METHODS: This multicenter, prospective, randomized, parallel trial enrolled patients for elective or urgent isolated coronary artery bypass grafting with an additive European System for Cardiac Operative Risk Evaluation of 6 or more. The patients in cardiogenic shock were excluded. The composite primary end point included operative mortality, myocardial infarction, stroke, renal failure, reoperation for bleeding and adult respiratory distress syndrome within 30 days after surgery. The total sample size was 693 patients, according to a scheduled interim analysis at 400 patients enrolled (α-spending = 0.029, Pocock method). RESULTS: A total of 411 patients were included in the interim analysis. Randomization assigned 203 patients to on-pump and 208 patients to off-pump treatment. Of the 411 patients, 24 crossed over; thus, 195 patients were actually treated on-pump and 216 off-pump. According to the intention to treat analysis, the rate of the composite primary end point was significantly lower (unadjusted P = .009, adjusted P = .010) in the off-pump group (5.8% vs 13.3%). The risk of experiencing the primary end point was significantly greater for the on-pump group (unadjusted odds ratio, 2.51; 95% confidence interval, 1.23-5.10; P = .011; adjusted odds ratio, 3.07; 95% confidence interval, 1.32-7.14; P = .009). CONCLUSIONS: Off-pump coronary artery bypass grafting reduces early mortality and morbidity in high-risk patients.

CArdiac resynchronization in combination with beta blocker treatment in advanced chronic heart failure (CARIBE-HF): the results of the CARIBE-HF study.

OBJECTIVE: Cardiac resynchronization therapy (CRT), combined with optimal medical therapy (OMT), is an established treatment for patients with advanced chronic heart failure (ACHF). In ACHF, carvedilol at the dose used in clinical trials, reduces morbidity and mortality. However, patients often do not tolerate the drug at the targeted dosage. The aim of the CARIBE-HF prospective observational study was to investigate the role of CRT in the implementation of carvedilol therapy in patients with ACHF. METHODS: One hundred and six patients (aged 65 12 [mean +/- SD] years) with ACHF were enrolled and treated with OMT, in which carvedilol was titrated up to the maximal dose (phase 1). Subsequently, patients with left ventricular (LV) ejection fraction < or = 35%, NYHA class III-IV and QRS interval > or =120 msec were assigned to CRT. Both CRT and NO-CRT patients underwent a long-term follow-up of 7 years (1193.98 +/- 924 days), while efforts to up titrate the carvedilol dose were continued during the second phase (471 + 310 days). Phase 1 was completed by 84 patients (79%), and 15 (18%) underwent CRT. The mean carvedilol dose in the CRT group was 19.0 +/- 17.8 mg, against 32.7 +/- 19.1 mg in the remaining 69 patients (P = 0.018). At the end of phase 2, CRT patients presented a significantly greater variation of increasing in the carvedilol dose than NO-CRT patients (+20.0 +/- 19.8 mg vs. -0.3 +/- 20.5 mg; P = 0.015), a greater NYHA class reduction (-0.8 +/- 0.6 vs. -0.2 +/- 0.7; P = 0.011), and a greater increase in LV ejection fraction (10.8 +/- 9 vs. 3.1 +/- 6.1; P = 0.018). CONCLUSIONS: The data from the CARIBE study suggest that, in ACHF, CRT may be effective in enabling the target dose of carvedilol to be reached. The significant improvement seen in LV function was probably due to a synergistic effect of CRT and carvedilol. During the extended follow-up (mean 1193.98 +/- 924 days) the mean dosage of carvedilol in the CRT group was significantly higher (P < 0.02).

Predictive value of microvolt T-wave alternans for cardiac death or ventricular tachyarrhythmic events in ischemic and nonischemic cardiomyopathy patients: a meta-analysis.

BACKGROUND: Microvolt T-wave alternans (MTWA) has been proposed as a predictor of the risk of ventricular tachyarrhythmias (VT) and sudden cardiac death (SCD). Aim of this study was to perform a systematic review of the literature and a meta-analysis of MTWA in primary prevention patients with ischemic and nonischemic cardiomyopathy. METHODS: The positive predictive value (PPV), negative predictive value (NPV), and relative risk (RR) of MTWA in predicting death, cardiac death, and SCD during follow-up were reported. RESULTS: Fifteen studies involving 5681 patients (mean age 62 years, mean ejection fraction 32%) were included. The summary PPV during the average 26-month follow-up was 14% (95% CI: 13-15); NPV was 95% (95% CI: 94-96), and the univariate RR was 2.35 (95% CI: 1.68-3.28). The predictive value of MTWA was similar in patients with ischemic and nonischemic cardiomyopathy. The average RR for SCD or VT events of an abnormal MTWA was 2.40, similar to that for cardiac death. When we grouped the studies together depending upon whether beta-blockers were withheld prior to MTWA screening, the beta-blockers group showed an RR of 5.88. By contrast, the group in which beta-blocker therapy was withheld had an RR of 1.63. CONCLUSION: A positive MTWA determined an approximately 2.5-fold higher risk of cardiac death and life-threatening arrhythmia and showed a very high NPV both in ischemic and nonischemic patients. An abnormal MTWA test was associated with a 5-fold increased risk for cardiac mortality in the low-indeterminate group and about a 6-fold increased risk in beta-blockers group.

Improving stroke risk stratification using the CHADS2 and CHA2DS2-VASc risk scores in patients with paroxysmal atrial fibrillation by continuous arrhythmia burden monitoring.

BACKGROUND AND PURPOSE: In patients with atrial fibrillation (AF), stroke risk stratification schema do not consider AF parameters. The aim of the study is to assess the impact of combining risk factors with continuous AF burden monitoring. METHODS: In this retrospective study 568 patients implanted with a DDDR-P pacemaker (AT-500; Medtronic) and a history of AF were continuously monitored for 1 year. RESULTS: During follow-up, 14 patients (2.5%) had a thromboembolic event. Patients were divided into 3 groups: AF burden ≤5 minutes per day (AF-free; n=223 [39%]), AF burden >5 minutes but <24 hours per day (AF-5 minutes; n=179 [32%]), and AF burden ≥24 hours (AF-24 hours; n=166 [29%]). Patients were also classified according to CHADS2 and CHA2DS2-VASc risk scores. The discrimination ability of each risk score was evaluated performing a logistic regression analysis and calculating the corresponding C-statistic. The addition of AF burden improved C-statistics: for CHADS2 from 0.653 (P=0.051) to 0.713 (P=0.007); for CHA2DS2-VASc, from 0.898 (P<0.0001) to 0.910 (P<0.0001). CONCLUSIONS: The CHA2DS2-VASc score had a high sensitivity to predict thromboembolism. Implementation of device data on AF presence/duration/burden has the potential to contribute to improved clinical risk stratification and should be tested prospectively.

Physiopathologic correlates of intrathoracic impedance in chronic heart failure patients.

BACKGROUND: Increased plasma levels of amino-terminal fraction of brain natriuretic peptide (NT-proBNP) and alterations of diastolic filling as described by Doppler transmitral flow pattern are well-known markers of decompensated heart failure (HF). Recently, some implantable defibrillators have allowed monitoring of intrathoracic impedance, which is related to lung water content, potentially indicating HF deterioration. The aim of this study was to assess the correlation between intrathoracic impedance and NT-proBNP and echo-Doppler transmitral flow indexes. METHODS: Data were collected from 111 HF patients, in six Italian centers. All patients were on optimal medical therapy. Device diagnostics, echographic data, NT-proBNP determination, and clinical status as assessed by the Heart Failure Score (HFS) were registered at baseline, at bimonthly visits, and at unscheduled examinations due to HF decompensation or device alerts. RESULTS: Over a median follow-up of 413 days, 955 examinations were performed. Intrathoracic impedance was significantly correlated with NT-proBNP (P = 0.013) and with mitral E-wave deceleration time (DtE) (P = 0.017), but not with HFS. At the time of confirmed alert events, NT-proBNP was significantly higher than during confirmed nonalert event examinations; DtE did not differ, whereas impedance was significantly lower. CONCLUSION: A decrease in intrathoracic impedance is inversely correlated with NT-proBNP and directly correlated with DtE. Intrathoracic impedance monitoring therefore has the physiologic basis for being a useful tool to identify early HF decompensation.

BIVentricular versus right ventricular antitachycardia pacing to terminate ventricular tachyarrhythmias in patients receiving cardiac resynchronization therapy: the ADVANCE CRT-D Trial.

BACKGROUND: This multicenter, prospective, randomized, controlled, parallel trial compares the efficacy of biventricular (BIV) versus right ventricular (RV) antitachycardia pacing (ATP) in terminating all kinds of ventricular tachycardia (VT). METHODS: Five hundred twenty-six patients implanted with a cardiac resynchronization therapy defibrillator (CRT-D) device were enrolled and randomized 1:1 to either BIV (266) or RV (260) ATP (single burst 8 pulse, 88% coupling interval) and were followed up for 12 months. RESULTS: During 12 months' follow-up, 1,077 ventricular episodes in 180 patients were detected and classified: 634 true VTs divided into 69 ventricular fibrillation (VF) (11%), 202 fast ventricular tachycardia (FVT) (32%), and 363 VT (57%). A comparable first ATP efficacy (BIV 65% vs RV 68%, P = .59) was observed in FVT + VT, in VT zone (BIV 62% vs RV 71%, P = .25), and in FVT zone (BIV 71% vs RV 61%, P = .34). A trend toward lower accelerations during ATP applied to FVT was observed in the BIV group (3.5% BIV vs 10.2% RV, P = .163). No syncope/presyncope occurred during ATP for FVT in the BIV group versus 4 events (3.2%) in the RV group (P = .016). biventricular ATP was more effective in treating FVT in coronary artery disease (CAD) patients (P = .032), whereas both modalities presented similar efficacy in patients with non-CAD etiology (P = .549). CONCLUSIONS: Antitachycardia pacing is effective in patients implanted with a CRT-D device. No significant differences in efficacy emerged between BIV- and RV-delivered ATP in the general population, whereas BIV ATP seems to present a safer profile in ischemic patients.

Early and late outcome of treated patients referred for syncope to emergency department: the EGSYS 2 follow-up study.

AIMS: We evaluated the early (1 month) and late (2 years) death rate and syncopal relapses of patients referred for syncope to 11 general hospitals emergency departments. Patients were enrolled in the Evaluation of Guidelines in SYncope Study 2 (EGSYS 2) study. The guidelines of the European Society of Cardiology were strictly followed in the management of patients. METHODS AND RESULTS: Out of the 465 patients enrolled in the EGSYS 2 study, 398 (86%) underwent a complete follow-up. We excluded 18 patients with non-syncopal attacks. Among the remaining 380 patients, death of any cause occurred in 35 (9.2%). The mean follow-up was 614 +/- 73 days. Six deaths (17% of total) occurred during the first month of follow-up. Patients who died were older, had a higher incidence of structural heart disease and/or abnormal ECG, had injuries related to syncope and higher EGSYS score. Syncope recurred in 63 (16.5%) patients. Syncopal relapses occurred in only one patient during the first month of follow-up. The incidence of syncopal recurrences was unrelated to the mechanism of syncope. No clinical differences were found between patients with or without syncopal recurrence and in patients with EGSYS score < or >or=3. CONCLUSION: A peak of cardiovascular mortality but not of syncopal recurrences was observed in patients attending to the emergency department for syncope within the first month. Late unfavourable outcomes were caused by associated cardiovascular diseases rather than by the mechanism of syncope. The causes of syncope did not determine the recurrence rate.

Prospective multicenter randomized trial of fast ventricular tachycardia termination by prolonged versus conventional anti-tachyarrhythmia burst pacing in implantable cardioverter-defibrillator patients-Atp DeliVery for pAiNless ICD thErapy (ADVANCE-D) Trial results.

PURPOSE: The purpose of the trial was to quantify and compare the efficacy of two different sequences of burst anti-tachycardia pacing (ATP) strategies for the termination of fast ventricular tachycardia. METHODS: The trial was prospective, multicenter, parallel and randomized, enrolling patients with an indication for implantable cardioverter-defibrillator implantation. RESULTS: From February 2004, 925 patients were randomized and followed-up for 12 months. Eight pulses ATP terminated 64% of episodes vs. 70% in the 15-pulse group (p = 0.504). Fifteen pulses proved significantly better in patients without a previous history of heart failure (p = 0.014) and in patients with LVEF >or= 40% (p = 0.016). No significant differences between groups were observed with regard to syncope/near-syncope occurrence. CONCLUSION: In the general population, 15-pulse ATP is as effective and safe as eight-pulse ATP. The efficacy of ATP on fast ventricular arrhythmias confirmed once more the striking importance of careful device programming in order to reduce painful shocks.

Effectiveness of cardiac resynchronization therapy in heart failure patients with valvular heart disease: comparison with patients affected by ischaemic heart disease or dilated cardiomyopathy. The InSync/InSync ICD Italian Registry.

AIMS: To analyse the effectiveness of cardiac resynchronization therapy (CRT) in patients with valvular heart disease (a subset not specifically investigated in randomized controlled trials) in comparison with ischaemic heart disease or dilated cardiomyopathy patients. METHODS AND RESULTS: Patients enrolled in a national registry were evaluated during a median follow-up of 16 months after CRT implant. Patients with valvular heart disease treated with CRT (n = 108) in comparison with ischaemic heart disease (n = 737) and dilated cardiomyopathy (n = 635) patients presented: (i) a higher prevalence of chronic atrial fibrillation, with atrioventricular node ablation performed in around half of the cases; (ii) a similar clinical and echocardiographic profile at baseline; (iii) a similar improvement of LVEF and a similar reduction in ventricular volumes at 6-12 months; (iv) a favourable clinical response at 12 months with an improvement of the clinical composite score similar to that occurring in patients with dilated cardiomyopathy and more pronounced than that observed in patients with ischaemic heart disease; (v) a long-term outcome, in term of freedom from death or heart transplantation, similar to patients affected by ischaemic heart disease and basically more severe than that of patients affected by dilated cardiomyopathy. CONCLUSION: In 'real world' clinical practice, CRT appears to be effective also in patients with valvular heart disease. However, in this group of patients the outcome after CRT does not precisely overlap any of the two other groups of patients, for which much more data are currently available.

Primary prevention implantation of cardioverter defibrillator without defibrillation threshold testing: 2-year follow-up.

BACKGROUND: Even though the intraoperative threshold testing of the implantable cardioverter defibrillator (ICD) may cause hemodynamic impairment or be unfeasible, it is still considered required standard practice at the time of implantation. We compared the outcome of ICD recipients who underwent defibrillation threshold testing (DFT) with that of patients in whom no testing was performed. METHODS: A total of 291 subjects with ischemic dilated cardiomyopathy received transvenous ICDs between January 2000 and December 2004 in five Italian cardiology centers. In two centers, DFT was routinely performed in 137 patients (81% men; mean age 69+/-9 years; mean ejection fraction 26+/-4%) (DFT group), while three centers never performed DFT in 154 patients (90% men; mean age 69+/-9 years; mean ejection fraction 27+/-5%) (no-DFT group). RESULTS: We compared total mortality, total cardiovascular mortality, sudden cardiac death (SCD), and spontaneous episodes of ventricular arrhythmia (sustained ventricular tachycardia, VT, and ventricular fibrillation, VF) between these groups 2 years after implantation (median 23 months, 25th-75th percentile, 12-44 months). On comparing the DFT and no-DFT groups, we found an overall mortality rate of 20% versus 16%, cardiovascular mortality of 13% versus 10%, SCD of 3% versus 0.6%, VT incidence of 8% versus 10%, and VF incidence of 6% versus 4% (no significant difference in any comparison). CONCLUSIONS: No significant differences in the incidence of clinical outcomes considered emerged between no-DFT and DFT groups. These results should be confirmed in larger prospective studies.

Heart rate variability monitored by the implanted device predicts response to CRT and long-term clinical outcome in patients with advanced heart failure.

BACKGROUND: Few data exist on the long-term changes and the prognostic value of heart rate variability (HRV) assessed by implanted devices in heart failure (HF) patients treated with resynchronization therapy (CRT). AIMS: To analyze the long-term changes in the standard deviation of 5-minute median atrial-atrial sensed intervals (SDANN), and assess its role in predicting CRT efficacy and major cardiovascular events. METHODS AND RESULTS: We included 509 consecutive patients implanted with CRT devices. At 12-month follow-up, 44 patients had died and 86 patients had at least one HF hospitalisation. A significant increase in SDANN occurred after 4 weeks of CRT (from 69+/-22 ms to 82+/-27 ms, p<0.001). A further increase in SDANN was observed 6 months after implantation. Multivariable analysis identified SDANN as the sole predictor of major cardiovascular events (p=0.03) among several baseline parameters. SDANN< or =65 ms at the first week and SDANN< or =76 ms after 4 weeks of CRT yielded the best prediction of all-cause mortality and urgent heart transplantation on Kaplan-Meier analysis (log-rank test p=0.015 and p=0.011, respectively for week 1 and 4 values). Moreover, relative reduction in LVESV after CRT significantly correlated with SDANN at week 1 (r=-0.596, p=0.012), and week 4 (r=-0.703, p=0.001). CONCLUSIONS: Device-monitored HRV is a useful tool to identify, early after implantation, patients with a low likelihood of long-term benefits from CRT and at high risk for cardiovascular events.

Management of syncope: clinical and economic impact of a Syncope Unit.

AIMS: Aim of this observational study is to evaluate the clinical performance of a Syncope Unit, in order to assess whether the implemented organization really improves syncope management. METHODS AND RESULTS: The study enrolled patients with unexplained syncope who were consecutively referred to our Syncope Unit, either as outpatients or during hospitalization, in a 2-month period. The design of this observational study consists in three phases: a retrospective analysis of their clinical management in the 9 months prior to the first attendance at the Syncope Unit (phase one), their subsequent clinical management in the Syncope Unit (phase two) and a 9-month follow-up (phase three). The retrospective analysis of phase one showed that 25% of patients had already been hospitalized without diagnosis. After Syncope Unit evaluation, diagnosis was obtained in 82% of patients, with 15% of patients indicated to pacing. In the follow-up, 23% of patients experienced a syncopal recurrence. Our analysis indicated an 85% reduction of hospital costs in the follow-up period. CONCLUSION: The clinical and economic analysis of the three phases of our study demonstrates that a Syncope Unit allows an improved management of patients with syncope.

Circadian pattern of atrial pacing threshold in the young.

AIM: The aim of this study was to evaluate the circadian variation of atrial pacing threshold in young patients. METHODS AND RESULTS: Atrial Capture Management (ACM) algorithm is a Medtronic EnPulse pacemaker (PM) feature that uses two algorithms: atrioventricular conduction (AVC) (atrial pacing and spontaneous AVC) and atrial chamber reset (ACR) [intrinsic atrial activity with atrioventricular block (AVB)]. For this prospective, non-randomized study, ACM automatically measured and recorded thresholds every 4 h. Data are reported as median (range) or mean +/- SD. In 2004-05, 14 consecutive patients (11 males, 79%), aged 12 years (1 day-24 years) received an EnPulse DDD/R PM for AVB (eight patients, 57%) or sinus node dysfunction. A new pacing system was implanted in eight patients (57%) and a replaced PM in six patients. Epicardial leads were implanted in 10 patients (71%). The follow-up duration is 11 (1-18) months: 9742 threshold measurements were attempted (6328 AVC, 3414 ACR), of which 3797 (39%) were successful (1807 AVC, 29%, 1990 ACR, 58%) in 11 (79%) patients. Three infants had no successful measurements. Measurement success was 42 +/- 34% (AVC 27 +/- 39%, ACR 41 +/- 29%). Higher thresholds were found between 00.00 and 12.00 a.m. and lower between 12.00 and 20.00. CONCLUSION: Young patients show a circadian variability of atrial threshold with higher thresholds between 00.00 and 12.00.

Atrial threshold variability: implications for automatic atrial stimulation algorithms.

BACKGROUND: Automatic management of atrial stimulation by verification of atrial threshold (ACM) has recently been made feasible. We investigated circadian atrial threshold variability over the long term and the predictors of successful automatic atrial threshold measurement, in order to provide practical clues for programming ACM features, in such a way as to achieve daily threshold verification and > 99% effective atrial stimulation. METHODS: Six daily attempts to measure atrial threshold were programmed in patients receiving an EnPulse pacemaker (Medtronic Inc., Minneapolis, MN, USA). Atrioventricular (AV) conduction was maximized by programming Search AV+ (SAV+) to a resting Paced AV delay = 400 ms in the first month, and 600 ms thereafter. RESULTS: Seventy-six patients had a median follow-up of 12 months. Median ACM success was 77%. Concordance between automatically and manually measured thresholds was observed during the entire follow-up (Rho = 0.82, P < 0.001). Daily variability in atrial threshold was < 0.5 V in > 94% of measurements in the first trimester after implantation, and < 0.5 V in > 99% of measurements thereafter, as well as any time after pacemaker replacement. Atrial threshold was measured on 86% of days: the predictors of ACM failure were AV block (AVB), high%Atrial pacing, and atrial fibrillation. Programming SAV+ to achieve 600 ms resting Paced AV decreased%Vpacing in patients with normal AV conduction and first-degree AVB, improving the ability to detect atrial threshold. CONCLUSIONS: The reliability of ACM is high over a long follow-up. On the basis of atrial threshold variability, a practical approach to ACM programming should be two daily atrial threshold measurements in patients with normal AV conduction and%Ap < or = 40%, or with normal sinus activity and AVB, whereas 3-4 measurements should be recommended in patients with first-degree AVB and%Ap > 40% or with recurrent atrial fibrillation and AVB. The lowest adapted stimulation output should achieve at least threshold +1 V in the first trimester after implantation, then threshold +0.5 V thereafter, in order to achieve > 99.5% effective atrial stimulation.