Closed loop stimulation reduces the incidence of atrial high-rate episodes compared with conventional rate-adaptive pacing in patients with sinus node dysfunctions.

AIMS: Subclinical atrial fibrillation (AF) is associated with increased risk of progression to clinical AF, stroke, and cardiovascular death. We hypothesized that in pacemaker patients requiring dual-chamber rate-adaptive (DDDR) pacing, closed loop stimulation (CLS) integrated into the circulatory control system through intra-cardiac impedance monitoring would reduce the occurrence of atrial high-rate episodes (AHREs) compared with conventional DDDR pacing. METHODS AND RESULTS: Patients with sinus node dysfunctions (SNDs) and an implanted pacemaker or defibrillator were randomly allocated to dual-chamber CLS (n = 612) or accelerometer-based DDDR pacing (n = 598) and followed for 3 years. The primary endpoint was time to the composite endpoint of the first AHRE lasting ≥6 min, stroke, or transient ischaemic attack (TIA). All AHREs were independently adjudicated using intra-cardiac electrograms. The incidence of the primary endpoint was lower in the CLS arm (50.6%) than in the DDDR arm (55.7%), primarily due to the reduction in AHREs lasting between 6 h and 7 days. Unadjusted site-stratified hazard ratio (HR) for CLS vs. DDDR was 0.84 [95% confidence interval (CI), 0.72-0.99; P = 0.035]. After adjusting for CHA2DS2-VASc score, the HR remained 0.84 (95% CI, 0.71-0.99; P = 0.033). In subgroup analyses of AHRE incidence, the incremental benefit of CLS was greatest in patients without atrioventricular block (HR, 0.77; P = 0.008) and in patients without AF history (HR, 0.73; P = 0.009). The contribution of stroke/TIA to the primary endpoint (1.3%) was low and not statistically different between study arms. CONCLUSION: Dual-chamber CLS in patients with SND is associated with a significantly lower AHRE incidence than conventional DDDR pacing.

Device-detected atrial sensing amplitudes as a marker of increased risk for new onset and progression of atrial high-rate episodes.

BACKGROUND: Atrial high-rate episodes (AHREs) are frequent in patients with cardiac implantable electronic devices. A decrease in device-detected P-wave amplitude may be an indicator of periods of increased risk of AHRE. OBJECTIVE: The objective of this study was to assess the association between P-wave amplitude and AHRE incidence. METHODS: Remote monitoring data from 2579 patients with no history of atrial fibrillation (23% pacemakers and 77% implantable cardioverter-defibrillators, of which 40% provided cardiac resynchronization therapy) were used to calculate the mean P-wave amplitude during 1 month after implantation. The association with AHRE incidence according to 4 strata of daily burden duration (≥15 minutes, ≥6 hours, ≥24 hours, ≥7 days) was investigated by adjusting the hazard ratio with the CHA2DS2-VASc score. RESULTS: The adjusted hazard ratio for 1-mV lower mean P-wave amplitude during the first month increased from 1.10 (95% confidence interval [CI], 1.05-1.15; P < .001) to 1.18 (CI, 1.09-1.28; P < .001) with AHRE duration strata from ≥15 minutes to ≥7 days independent of the CHA2DS2-VASc score. Of 871 patients with AHREs, those with 1-month P-wave amplitude <2.45 mV had an adjusted hazard ratio of 1.51 (CI, 1.19-1.91; P = .001) for progression of AHREs from ≥15 minutes to ≥7 days compared with those with 1-month P-wave amplitude ≥2.45 mV. Device-detected P-wave amplitudes decreased linearly during the 1 year before the first AHRE by 7.3% (CI, 5.1%-9.5%; P < .001 vs patients without AHRE). CONCLUSION: Device-detected P-wave amplitudes <2.45 mV were associated with an increased risk of AHRE onset and progression to persistent forms of AHRE independent of the patient's risk profile.

Prognostic significance of remotely monitored nocturnal heart rate in heart failure patients with reduced ejection fraction.

BACKGROUND: Elevated resting heart rate is a risk factor for cardiovascular events. OBJECTIVE: The purpose of this study was to investigate the clinical significance of nocturnal heart rate (nHR) and 24-hour mean heart rate (24h-HR) obtained by continuous remote monitoring (RM) of implantable devices. METHODS: We analyzed daily-sampled trends of nHR, 24h-HR, and physical activity in patients on ß-blocker therapy for chronic heart failure and with implantable cardioverter-defibrillators or cardiac resynchronization therapy defibrillators (CRT-Ds). Patients were grouped by average nHR and 24h-HR quartile during follow-up to estimate the respective incidence of nonarrhythmic death and device-treated ventricular tachycardia/fibrillation (VT/VF). RESULTS: The study cohort included 1330 patients (median age 69 years [interquartile range 61-77 years]; 41% [n = 550] with CRT-D; median follow-up 25 months [interquartile range 13-42 months]). Compared with patients in the lowest nHR quartile (≤57 beats/min) group, patients in the highest quartile group (>65 beats/min) had an increased risk of nonarrhythmic death (adjusted hazard ratio [AHR] 2.25; 95% confidence interval [CI] 1.13-4.50; P = .021) and VT/VF (AHR 1.98; 95% CI 1.40-2.79; P < .001) and were characterized by the lowest level of physical activity (P ≤ .0004 vs every other nHR quartiles). The highest 24h-HR quartile group (>75 beats/min) showed an increased risk of VT/VF (AHR 2.13; 95% CI 1.52-2.99; P < .001) and a weaker though significant association with nonarrhythmic mortality (AHR 1.80; 95% CI 1.00-3.22; P = .05) as compared with the lowest 24h-HR quartile group (≤65 beats/min). CONCLUSION: In remotely monitored patients with implantable cardioverter-defibrillator/CRT-D on ß-blocker therapy for heart failure, elevated heart rates (nHR >65 beats/min and 24h-HR >75 beats/min) were associated with increased mortality and VT/VF risk. nHR showed a stronger association than 24h-HR with worst prognosis and lowest physical activity.

Ventricular Arrhythmias and Implantable Cardioverter-Defibrillator Therapy in Women: A Propensity Score-Matched Analysis.

BACKGROUND: Causes of sex differences in incidence of sustained ventricular arrhythmias (SVAs) are poorly understood. OBJECTIVES: This study aims to investigate sex-specific risk of SVAs and device therapies by balancing sex groups in relation to several baseline characteristics with the propensity score (PS). METHODS: We used a large remote monitoring dataset from implantable cardioverter-defibrillators (ICDs) and cardiac resynchronization therapy defibrillators (CRT-Ds). Study endpoints were time to the first appropriate SVA, time to the first device therapy for SVA, and time to the first ICD shock. Results were compared between females and a PS-matched male subgroup. RESULTS: In a cohort of 2,532 patients with an ICD or CRT-D (median age, 70 years), 488 patients (19.3%) were women. After selecting 488 men PS-matched for 19 variables relative to baseline demographics, implant indications, principal comorbidities, and concomitant therapy, yet the SVA rate at the 2.1-year median follow-up was significantly lower in women than in man (adjusted HR: 0.65; 95% CI: 0.51-0.81; P < 0.001). Women also showed a reduced risk of any device therapy (HR: 0.59; 95% CI: 0.45-0.76; P < 0.001) and shocks (HR: 0.66; 95% CI: 0.47-0.94; P = 0.021). Differences in sex-specific SVA risk profile were not confirmed in CRT-D patients (HR: 0.78; 95% CI: 0.55-1.09; P = 0.14) nor in those with an ejection fraction <30% (HR: 0.80; 95% CI: 0.52-1.23; P = 0.31). CONCLUSIONS: After matching demographics, indications, principal comorbidities, and concomitant therapy, women still exhibited a lower SVA risk profile than men, except in the subgroups of CRT-D or/and ejection fraction <30%.

One-year mortality after implantable defibrillator implantation: do risk stratification models help improving clinical practice?

PURPOSE: The purpose of this study was to assess the available mortality risk stratification models for implantable cardioverter defibrillator (ICD) and cardiac resynchronization therapy defibrillator (CRT-D) patients. METHODS: We conducted a review of mortality risk stratification models and tested their ability to improve prediction of 1-year survival after implant in a database of patients who received a remotely controlled ICD/CRT-D device during routine care and included in the independent Home Monitoring Expert Alliance registry. RESULTS: We identified ten predicting models published in peer-reviewed journals between 2000 and 2021 (Parkash, PACE, MADIT, aCCI, CHA2DS2-VASc quartiles, CIDS, FADES, Sjoblom, AAACC, and MADIT-ICD non-arrhythmic mortality score) that could be tested in our database as based on common demographic, clinical, echocardiographic, electrocardiographic, and laboratory variables. Our cohort included 1,911 patients with left ventricular dysfunction (median age 71, 18.3% female) from sites not using any risk stratification score for systematic patient screening. Patients received an ICD (53.8%) or CRT-D (46.2%) between 2011 and 2017, after standard physician evaluation. There were 56 deaths within 1-year post-implant, with an all-cause mortality rate of 2.9% (95% confidence interval [CI], 2.3-3.8%). Four predicting models (Parkash, MADIT, AAACC, and MADIT-ICD non-arrhythmic mortality score) were significantly associated with increased risk of 1-year mortality with hazard ratios ranging from 3.75 (CI, 1.31-10.7) to 6.53 (CI 1.52-28.0, p ≤ 0.014 for all four). Positive predictive values of 1-year mortality were below 25% for all models. CONCLUSION: In our analysis, the models we tested conferred modest incremental predicting power to ordinary screening methods.

Circadian periodicity affects the type of ventricular arrhythmias and efficacy of implantable defibrillator therapies.

INTRODUCTION: Factors influencing malignant arrhythmia onset are not fully understood. We explored the circadian periodicity of ventricular arrhythmias (VAs) in patients with implantable cardioverter and cardiac resynchronization defibrillators (ICD/CRT-D). METHODS: Time, morphology (monomorphic/polymorphic), and mode of termination (anti-tachycardia pacing [ATP] or shock) of VAs stored in a database of remote monitoring data were adjudicated. Episodes were grouped in six 4-h timeslots from 00:00 to 24:00. Circadian distributions and adjusted marginal odds ratios (ORs), with 95% confidence interval (CI), were analyzed using mixed-effect models and logit generalized estimating equations, respectively, to account for within-subject correlation of multiple episodes. RESULTS: Among 1303 VA episodes from 446 patients (63% ICD and 37% CRT-D), 120 (9%) self-extinguished, and 842 (65%) were terminated by ATP, 343 (26%) by shock. VAs clustered from 08:00 to 16:00 with 44% of episodes, as compared with 22% from 00:00 to 08:00 (p < .001) and 34% from 16:00 to 24:00 (p = .005). Episodes were more likely to be polymorphic at night with an adjusted marginal OR of 1.66 (CI, 1.15-2.40; p = .007) at 00:00-04:00 versus other timeslots. Episodes were less likely to be terminated by ATP in the 00:00-04:00 (success-to-failure ratio, 0.67; CI, 0.46-0.98; p = .039) and 08:00-12:00 (0.70; CI, 0.51-0.96; p = .02) timeslots, and most likely to be terminated by ATP between 12:00 and 16:00 (success-to-failure ratio 1.42; CI, 1.06-1.91; p = .02). CONCLUSION: VAs did not distribute uniformly over the 24 h, with a majority of episodes occurring from 08:00 to 16:00. Nocturnal episodes were more likely to be polymorphic. The efficacy of ATP depended on the time of delivery.

Home delivery of the communicator for remote monitoring of cardiac implantable devices: A multicenter experience during the covid-19 lockdown.

BACKGROUND: During the COVID-19 pandemic in-person visits for patients with cardiac implantable electronic devices should be replaced by remote monitoring (RM), in order to prevent viral transmission. A direct home-delivery service of the RM communicator has been implemented at 49 Italian arrhythmia centers. METHODS: According to individual patient preference or the organizational decision of the center, patients were assigned to the home-delivery group or the standard in-clinic delivery group. In the former case, patients received telephone training on the activation process and use of the communicator. In June 2020, the centers were asked to reply to an ad hoc questionnaire to describe and evaluate their experience in the previous 3 months. RESULTS: RM was activated in 1324 patients: 821 (62%) received the communicator at home and the communicator was activated remotely. Activation required one additional call in 49% of cases, and the median time needed to complete the activation process was 15 min [25th-75th percentile: 10-20]. 753 (92%) patients were able to complete the correct activation of the system. At the time when the questionnaire was completed, 743 (90%) communicators were regularly transmitting data. The service was generally deemed useful (96% of respondents) in facilitating the activation of RM during the COVID-19 pandemic and possibly beyond. CONCLUSIONS: Home delivery of the communicator proved to be a successful approach to system activation, and received positive feedback from clinicians. The increased use of a RM protocol will reduce risks for both providers and patients, while maintaining high-quality care.

The role of atrial sensing for new-onset atrial arrhythmias diagnosis and management in single-chamber implantable cardioverter-defibrillator recipients: Results from the THINGS registry.

INTRODUCTION: Atrial tachycardia/fibrillation (AT/AF) episodes are common in implantable cardioverter-defibrillator (ICD) recipients and can be undetected by standard single-chamber devices. This study aims to explore whether a single-lead ICD with an atrial dipole (ICD DX; BIOTRONIK SE & Co, Berlin, Germany) could improve the AT/AF diagnosis and management as compared to standard ICD (ICD VR). METHODS AND RESULTS: We selected patients without AT/AF history from the THINGS registry which included consecutive patients implanted with ICD for standard indications. The ICD VR and the ICD DX groups included 236 (62.8%) and 140 (37.2%) patients, respectively, and had no significant differences in baseline characteristics. During a median follow-up of 27 months, there were 7 AT/AF diagnoses in the ICD VR and 18 in the ICD DX group. The 2-year incidence of AT/AF diagnosis was 3.6% (95% confidence interval [CI]: 1.6%-9.6%) for the ICD VR and 11.4% (95% CI: 6.8%-18.9%) for the ICD DX group (adjusted hazard ratio [HR]: 3.85 [95% CI: 1.58-9.41]; P = .003). Initiation of oral anticoagulation (OAC) due to AT/AF diagnosis was reported in 15 patients. The 2-year incidence of OAC onset was 3.6% (95% CI: 1.6%-7.8%) for the ICD VR and 6.3% (95% CI: 3.0%-12.7%) for ICD DX group (adjusted HR: 1.99 [95% CI: 0.72-5.56]; P = .184). CONCLUSION: We observed that atrial sensing capability in single-chamber ICD patients without evidence of atrial arrhythmias at implant is associated with a greater likelihood of detecting AT/AF episodes. The management of these diagnosed arrhythmias often led to clinical interventions, mainly represented by initiation of OAC therapy.

Real-life outcome of implantable cardioverter-defibrillator and cardiac resynchronization defibrillator replacement/upgrade in a contemporary population: observations from the multicentre DECODE registry.

AIMS: The benefit of prolonged implantable cardioverter-defibrillator (ICD)/cardiac resynchronization therapy defibrillator (CRT-D) therapy following device replacement is hindered by clinical and procedure-related adverse events (AEs). Adverse events rate is highest in more complex devices and at upgrades, as per the REPLACE registry experience, but is changing owing to the improvement in device technology and medical care. We aimed at understanding the extent and type of AEs in a contemporary Italian population. METHODS AND RESULTS: Detect long-term complications after ICD replacement (DECODE) was a prospective, single-arm, multicentre cohort study aimed at estimating medium- to long-term AEs in a large population of patients undergoing ICD/cardiac resynchronization defibrillator replacement/upgrade from 2013 to 2015. We prospectively analysed all clinical and device-related AEs at 12-month follow-up (FU) of 983 consecutive patients (median age 71 years, 76% male, 55% ischaemic, 47% CRT-D) followed for 353 ± 49 days. Seven percent of the patients died (60.6% for cardiovascular reasons), whereas 104 AEs occurred; 43 (4.4%) patients needed at least one surgical action to treat the AE. Adverse events rates were 3.3/100 years lead-related, 3.4/100 years bleedings, and 1.6/100 years infective. The primary endpoint was predicted by hospitalization in the month prior to the procedure [hazard ratio (HR) = 2.23, 1.16-4.29; 0.0169] and by upgrade (HR = 1.75, 1.02-2.99, 0.0441). One hundred and twelve (11.4%) patients met the combined endpoint of death from any cause, cardiac implantable electronic device (CIED)-related infection, and surgical action/hospitalization required to treat the AE. Hospitalization within 30 days prior to the procedure (HR = 2.07, 1.13-3.81; 0.0199), anticoagulation (HR = 1.97, 1.26-3.07; 0.003), and ischaemic cardiomyopathy (HR = 1.67, 95% confidence interval 1.06-2.63; P = 0.0276) were associated with the combined endpoint during FU. CONCLUSIONS: Adverse events following CIED replacement/upgrade are lower than previously reported, possibly owing to improved patients care. Hospitalization in the month prior to the procedure, upgrade, and clinical profile (anticoagulation, ischaemic cardiomyopathy) hint to increased risk, suggesting an individualized planning of the procedure to minimize overall AEs. CLINICAL TRIAL REGISTRATION: URL: http://clinicaltrials.gov/ Identifier: NCT02076789.

Impact of pacemaker longevity on expected device replacement rates: Results from computer simulations based on a multicenter registry (ESSENTIAL).

BACKGROUND: The rate of device replacement in pacemaker recipients has not been investigated in detail. HYPOTHESIS: Current pacemakers with automatic management of atrial and ventricular pacing output provide sufficient longevity to minimize replacement rate. METHODS: We considered a cohort of 542 pacemaker patients (age 78 ± 9 years, 60% male, 71% de-novo implants) and combined 1-month projected device longevity with survival data and late complication rate in a 3-state Markov model tested in several Monte Carlo computer simulations. Predetermined subgroups were: age < or ≥ 70; gender; primary indication to cardiac pacing. RESULTS: At the 1-month follow-up the reported projected device longevity was 153 ± 45 months. With these values the proportion of patients expected to undergo a device replacement due to battery depletion was higher in patients aged <70 (49.9%, range 32.1%-61.9%) than in age ≥70 (24.5%, range 19.9%-28.8%); in women (39.9%, range 30.8%-48.1%) than in men (32.0%, range 24.7%-37.5%); in sinus node dysfunction (41.5%, range 30.2%-53.0%) than in atrio-ventricular block (33.5%, range 27.1-38.8%) or atrial fibrillation with bradycardia (27.9%, range 18.5%-37.0%). The expected replacement rate was inversely related to the assumed device longevity and depended on age class: a 50% increase in battery longevity implied a 5% reduction of replacement rates in patients aged ≥80. CONCLUSIONS: With current device technology 1/4 of pacemaker recipients aged ≥70 are expected to receive a second device in their life. Replacement rate depends on age, gender, and primary indication owing to differences in patients' survival expectancy. Additional improvements in device service time may modestly impact expected replacement rates especially in patients ≥80 years.

Manufacturer change and risk of system-related complications after implantable cardioverter defibrillator replacement: physicians' survey and data from the Detect Long-term Complications After Implantable Cardioverter Defibrillator Replacement Registry.

AIMS: Some barriers seem to exist in changing implantable cardioverter defibrillator (ICD) manufacturer at the time of device replacement. We sought to understand the obstacles to changing ICD manufacturer within the cohort of patients enrolled in the Detect Long-term Complications After ICD Replacement Registry. METHODS: We analyzed 784 consecutive ICD/cardiac resynchronization therapy defibrillator (CRT-D) device replacements within a 1.5-year time-frame in 36 Italian centers to evaluate potential factors associated with changing manufacturers and system-related complications. RESULTS: Manufacturer change occurred in 191 patients (24%): 72/211 single-chamber ICDs (34%), 52/210 dual-chamber ICDs (25%) and 67/363 CRT-D (18%, P < 0.0001 vs. single-chamber). Replacement-only procedures were associated with a lower rate of manufacturer change than upgrading procedures (23 vs. 32%, P = 0.02). In the single-chamber/dual-chamber cohort, the only variables associated with manufacturer change were the number of available manufacturers (OR = 1.9; P < 0.0001) and an upgrade procedure (OR = 1.7; P = 0.035), whereas the center volume was associated with maintenance of the same manufacturer (OR = 0.5; P = 0.0172). In the CRT-D group, the number of available manufacturers [OR = 2.9; P < 0.0001, service life below the median value (OR = 2.5; P = 0.0026)], and physiological design (OR = 8.4; P = 0.0048) were associated with manufacturer change. At 6-month follow-up, 17 patients (2.2%) experienced a system complication that was lead-related in all cases; upgrade procedure was the only predictor (hazard ratio = 6.7) of complications. CONCLUSION: At the time of ICD replacement, a manufacturer change occurred in 24% of patients and it was less likely in CRT-D devices, which are equipped with more specific technology and less frequently require the addition of features. System-related complications are strongly associated to upgrade procedures rather than to manufacturer change.

Automatic management of atrial and ventricular stimulation in a contemporary unselected population of pacemaker recipients: the ESSENTIAL Registry.

AIMS: We investigated the applicability of the Ventricular Capture Control (VCC) and Atrial Capture Control (ACC) algorithms for automatic management of cardiac stimulation featured by Biotronik pacemakers in a broad, unselected population of pacemaker recipients. METHODS AND RESULTS: Ventricular Capture Control and Atrial Capture Control were programmed to work at a maximum adapted output voltage as 4.8 V in consecutive recipients of Biotronik pacemakers. Ambulatory threshold measurements were made 1 and 12 months after pacemaker implant/replacement in all possible pacing/sensing configurations, and were compared with manual measurements. Among 542 patients aged 80 (73-85) years, 382 had a pacemaker implant and 160 a pacemaker replacement. Ventricular Capture Control could work at long term in 97% of patients irrespectively of pacing indication, lead type, and lead service life, performance being superior with discordant pacing/sensing configurations. Atrial Capture Control could work in 93% of patients at 4.8 V maximum adapted voltage and at any pulse width, regardless of pacing indication, lead type, and service life. At 12-month follow-up, a ventricular threshold increase ≥1.5 V had occurred in 4.4% of patients uneventfully owing to VCC functioning. Projected pacemaker longevity at 1 month was strongly correlated with the 12-month estimate, and exceeded 13 years in >60% of patients. CONCLUSION: These algorithms for automatic management of pacing output ensure patient safety in the event of a huge increase of pacing threshold, while enabling maximization of battery longevity. Their applicability is quite broad in an unselected pacemaker population irrespectively of lead choice and service of life.

Left Ventricular Reverse Remodeling Elicited by a Quadripolar Lead: Results from the Multicenter Per4mer Study.

BACKGROUND: To understand the impact of a quadripolar left ventricular (LV) lead on reverse remodeling and phrenic nerve stimulation (PNS) in congestive heart failure patients treated by cardiac resynchronization therapy at 8-month follow-up (FU). METHODS: One hundred and fifty-eight patients received an LV Medtronic Performa lead (Medtronic Inc., Minneapolis, MN, USA) and were reevaluated at FU by echocardiography and measurement of electrical parameters. RESULTS: A targeted LV lead placement was achieved in 140 (89%) patients. Super responders and responders were 76 (50%) and 26 (18%), respectively, at FU; seven (4%) died and 13 (8%) were hospitalized for any cause. Nonischemic etiology was the only independent predictor of reverse remodeling. The configurations available only with the Performa leads reduced PNS occurrence at 8 V@0.4 ms from 43 (27%) to 14 (9%) of patients at implantation, and from 44 (28%) to 19 (12%) at last FU, compared to configurations available with bipolar leads. Patients with detectable PNS had >10/16 pacing configurations with a PNS safety margin >2 V both at implantation and at FU. During FU 16 (10%) patients had an adverse event possibly related to the lead or to modification of the underlying heart disease but 99% of these events were fixed by reprogramming of the pacing vector. CONCLUSIONS: Performa Lead enables an increased capability to achieve a targeted lead positioning in the broad clinical scenario of large- and small-volume implanting centers, with a relevant impact on the occurrence of reverse remodeling compared to literature data. The enhanced management of PNS resulted in a dislodgement rate of only 1%.

Long-term follow-up of patients with syncope evaluated by head-up tilt test.

BACKGROUND: Clinicians may be tempted to consider a positive head-up tilt test (HUTT) an unfavorable prognostic indicator. We investigated whether results of routine HUTT predict long-term recurrence of syncope. METHODS: We analyzed syncope recurrence at long-term among 107 patients (mean age 51 +/- 20 years) receiving HUTT for diagnostic evaluation of unexplained/suspected neurocardiogenic syncope in our Institute. RESULTS: HUTT was positive in 76 patients (vasodepressive response, n = 58; cardioinhibitory, n = 5; mixed, n = 13). During a median follow-up of 113 months (range, 7-161), 34 (32%) patients experienced recurrence (24 [32%] with positive HUTT during 110 months (7-159); 10 [32%] with negative HUTT during 120 [22-161] months). Actuarial freedom from recurrence at 10 years did not significantly differ for patients with positive/negative test results (after passive/active phases) or with different positive response patterns (vasodepressive, cardioinhibitory, mixed). By contrast, history of >4 syncopes in the 12 months preceding HUTT stratified risk of recurrence, irrespective of HUTT positivity/negativity. At Cox proportional hazards analysis, history of >4 syncopes in the 12 months preceding HUTT was the single independent risk factor for recurrence both in the overall study population (HR, 1.7; 95% CI, 1.07-2.69) and within the subset of patients who tested positive (HR, 1.83; 95% CI, 1.07-3.17). CONCLUSIONS: This long-term follow-up study reinforces the concept that a positive HUTT should not be considered an unfavorable prognostic indicator; frequency of recent occurrences may be a more valid predictor.

Actual pacemaker longevity: the benefit of stimulation by automatic capture verification.

BACKGROUND: We evaluated the impact of an algorithm for automatic right ventricular (RV) stimulation compared to fixed-output pacing (FOP) stimulation on actual pacemaker longevity over a 9-year follow-up. METHODS: Prospective observation of 300 patients implanted with VDDR/DDDR pacemakers in 1999-2000 up to October 31, 2008. Sixty-one patients were paced by Autocapture pacing (ACP), 239 were paced by FOP; they were seen twice yearly at the pacemaker clinic. Factors known to affect pacemaker longevity were collected: median heart rate, %A&V paced activity, pacing output, and impedance. Patients dead before pacemaker replacement, lost to follow-up, or who developed permanent atrial fibrillation were excluded from analysis. RESULTS: One hundred twenty-six of three hundred patients completed the study. Adverse clinical events due to an increased RV threshold occurred in two FOP patients compared to none among ACP. Pacemaker replacement occurred in 1/34 ACP patients versus 60/92 FOP patients (P < 0.001). ACP was the single independent predictor of pacemaker longevity at multivariable analysis (hazard ratio = 0.03, P < 0.001) either in the overall population or in the specific patients subgroups (sick sinus syndrome, atrioventricular block, and neurally mediated syncope). CONCLUSIONS: Automatic verification of stimulation is reliable at long term, and warrants superior safety in the event of pacing threshold changes. It allows a significant longevity increase compared to FOP stimulation that may heavily impact the patients' quality of life and the cost of pacing therapy. Moreover, it is a fundamental technology in a strategy of remote patient and device monitoring, and may enable automatic device follow-up operated by trained, nonmedical personnel.

Interventricular delay optimization: a comparison among three different echocardiographic methods.

AIM OF THE STUDY: To compare three different methods for obtaining interventricular-(VV) interval optimization. METHODS: A total of 30 patients undergoing cardiac resynchronization therapy (CRT) were enrolled. All the patients underwent VV-interval optimization performed with three different echocardiographic methods at seven different settings: simultaneous right (RV) and left (LV) ventricular pacing, LV stimulation only, LV preexcitation (LV+20,+40,+60 ms, respectively), RV preexcitation (RV+20 and+40 ms, respectively). Optimal VV delay was selected by: (1) measuring the aortic velocity time integral (VTI method); (2) measuring the time to maximum delay between septal and lateral longitudinal motion in the four-chamber view (velocity method); and (3) measuring the segment with maximal temporal difference of peak circumferential strain in short-axis view at papillary muscles level, (strain method). Velocity and strain methods measurements were obtained relying on two-dimensional ultrasound border tracking algorithm thus providing angle-independent measurements. RESULTS: Immediately after CRT, VTI, maximum peak circumferential strain delay and maximum septal-to-lateral delay were significantly improved (P < 0.001). Particularly, VV-interval optimization determined a further improvement of these indices as compared to the other VV settings (P < 0.001). Furthermore, a substantial concordance was found between the optimal VV interval obtained according to the VTI method and velocity method (k = 0.68), between the optimal VV interval obtained according to the VTI method and strain method (k = 0.63); and between the optimal VV interval obtained according to the velocity method and strain method (k = 0.71). CONCLUSIONS: VV-interval optimization was shown to determine a further benefit beyond CRT. A significant concordance was present between VV programming based on different echocardiographic methods.

Phrenic stimulation: a challenge for cardiac resynchronization therapy.

BACKGROUND: Phrenic stimulation (PS) may hinder left ventricular (LV) pacing. We prospectively observed its prevalence in consecutive patients with cardiac resynchronization therapy (CRT) devices. METHODS AND RESULTS: In the years 2003 to 2006, 197 patients received a CRT device. PS and LV threshold measurements were carried out at implantation and at 6-month follow-up. LV reverse remodeling was assessed by echocardiography before implantation and at follow-up. LV lead placement was lateral/posterolateral in 86% of patients. Both PS and LV reverse remodeling occurred most frequently at the lateral/posterolateral LV pacing sites (P<0.001). PS was detected in 73 (37%) of patients and was clinically relevant in 41 (22%). The detection of PS at implantation had a poor sensitivity, as it occurred only in left lateral or sitting position in 27 patients. Ten patients (5%) underwent repeated surgery and 4 (2%) had their CRT turned off because of PS. At follow-up, we could manage PS noninvasively in 32 patients with a small PS-LV threshold difference: in 20 by cathode programmability (3 also thanks to automatic management of LV output) and in 12 (without cathode programmability) by programming the LV output as threshold +1 V. CONCLUSIONS: PS may seriously hinder CRT. A bipolar LV lead and cathode programmability are mandatory to avoid PS by changing the LV pacing vector at target sites for CRT. LV stability at target sites despite PS should also be pursued by these means. The automatic adjustment of LV pacing output is complementary in patients with a small PS-LV threshold difference.

Troponin I rise after pacemaker implantation at the time of "universal definition of myocardial infarction".

We assessed incidence, magnitude, and time course of cardiac troponin I (cTnI) increase after pacemaker implantation in patients without acute coronary syndromes (ACSs). Seventy patients (mean age 71 years, interquartile range 44 to 92, 38 men) undergoing elective implantation of a single-/dual-chamber pacemaker with active/passive fixation leads were enrolled, excluding subjects with clinical suspicion of ACS, abnormal basal cTnI level, or presenting conditions predisposing to abnormal cTnI. Cardiac TnI concentrations were determined in basal conditions, at the end of the procedure, and after 8, 12, and 24 hours. Single-/dual-chamber devices were implanted in 31 of 39 patients. Cardiac TnI peak concentration occurred within the 12-hour assay in 69 of 70 patients; 26 of 70 had a cTnI above the normal cut-off range. All patients presented normal cTnI at 24-hour assay. In conclusion, pacemaker implantation is associated with increases of cTnI levels in up to 37% of patients. This can affect the specificity of cTnI assessment for ruling out ACS, especially within 12 hours after the procedure. These data deserve consideration in a contemporary setting, in which troponin has gathered a pivotal role in the diagnosis and therapy of ACS, and in particular clinical presentations in which electrocardiogram loses its diagnostic capabilities (due to paced rhythms) and symptoms may be lacking or confusing.