Initial heart rate score predicts new-onset atrial tachyarrhythmias in pacemaker patients.

AIMS: Heart rate score (HRSc), the per cent of atrial paced and sensed event in the largest 10 b.p.m. rate histogram bin of a pacemaker, predicts survival in patients with cardiac devices. No correlation between HRSc and development of atrial fibrillation (AF) has been reported. In this study, we evaluated the relationship between pacemaker post-implantation HRSc and the incidence of newly developed atrial tachyarrhythmias (ATAs). METHODS AND RESULTS: Patients with dual-chamber pacemakers, implanted 2013-17, with the LATITUDE remote monitoring data with ≥600 000 beats of histogram data collected at baseline were included (N = 34 543). Heart rate score was determined from the initial 3-month post-implantation histogram data. Patients were excluded if they had ATAs, defined as atrial high-rate episodes >5 min or >1% of right atrial beats >170 b.p.m. during the initial 3 months post-implantation. New ATAs, after the baseline period, were defined by each of the following: >1, >10, or >25% of atrial beats >170 b.p.m. or atrial tachycardia response (ATR) events >24 h. Patients were followed a median of 2.8 (1.0-4.0) years. The incidence of ATAs increased in proportion to HRSc (log-rank P-value <0.001), and the initial HRSc ≥70% was associated with increased ATAs by all definitions. Patients with initial HRSc ≥70% were older, had a higher percentage of right atrium pacing (%RA pacing), had a lower percentage of right ventricular pacing (%RV pacing), and were more likely programmed with rate-response vs. subjects with HRSc <70%. Initial HRSc (hazard ratio: 1.07, 95% confidence interval: 1.05-1.09; P < 0.0001) independently predicted ATAs after adjusting for age, gender, %RV pacing, and rate-response programming. The %RA pacing and initial HRSc were correlated. CONCLUSION: Heart rate score independently predicts any subsequent duration of ATAs in pacemaker patients.

Propensity score matched comparison of subcutaneous and transvenous implantable cardioverter-defibrillator therapy in the SIMPLE and EFFORTLESS studies.

Aims: Comparison of outcomes between subcutaneous and transvenous implantable cardioverter-defibrillator (S-ICD and TV-ICD) therapy is hampered by varying patient characteristics and complication definitions. The aim of this analysis is to compare clinical outcomes of S-ICD and TV-ICD therapy in a matched cohort. Methods and results: Patients implanted with de novo implantable cardioverter-defibrillators without need for pacing were selected from two studies: SIMPLE (n = 1091 single and n = 553 dual chamber TV-ICDs) and EFFORTLESS (n = 798 S-ICDs). Subcutaneous implantable cardioverter-defibrillator patients were 1:1 matched on propensity score to TV-ICD patients. Propensity scores were calculated using 15 baseline characteristics including diagnosis. The Kaplan-Meier estimates for complications requiring invasive intervention, appropriate shocks, and inappropriate shocks were calculated at 3 years follow-up. The primary analysis yielded 391 patients pairs with balanced baseline characteristics, with mean age 55 ± 14 years, 49% ischaemic cardiomyopathy, mean left ventricular ejection fraction 40%, 71% primary prevention, and 89% of TV-ICDs were single chamber. Follow-up was mean 2.9 years in the S-ICD arm vs. 3.3 in the TV-ICD arm. All-cause complications occurred in 9.0% of S-ICD vs. 6.5% of TV-ICD patients, P = 0.29. Appropriate shocks occurred in 9.9% of S-ICD vs. 13.8% in TV-ICD patients, P = 0.03 and inappropriate shocks in 11.9% in S-ICD vs. 8.9% in TV-ICD patients (P = 0.07). Total shock burden (20 vs. 31, P = 0.05) and appropriate shock burden per 100 patients years (9 vs. 18, P = 0.02) were lower for S-ICD patients, while inappropriate shock burden was equal (11 vs. 13, P = 0.56). Conclusion: The earliest experience of the S-ICD demonstrates similar outcomes as contemporary TV-ICD therapy in a matched comparison with predominately single-chamber devices at 3 years follow-up.

The rationale and design of the SMART CRT trial.

AIMS: The SMART CRT study will assess the efficacy of an atrioventricular optimization algorithm to improve reverse remodeling among patients undergoing cardiac resynchronization therapy (CRT) in the presence of interventricular electrical delay. METHODS AND RESULTS: The SMART CRT study is a global, multicenter, prospective, randomized study of patients undergoing CRT implantation. The primary endpoint of this trial is response rate to CRT, defined as decrease in left ventricular end-systolic volume (LVESV) ≥15% at 6 months compared to preimplant baseline. Additional prespecified analyses are: (1) clinical composite endpoint combining all-cause mortality, heart failure events, New York Heart Association class, and Quality of Life (using a patient global assessment instrument); (2) the individual components of the clinical composite endpoint; (3) 6-minute walk distance; (4) Kansas City Cardiomyopathy Questionnaire; (5) LVESV as a continuous variable; and (6) absolute left-ventricular ejection fraction. Subjects with intraventricular delay ≥ 70 ms measured between the right ventricular and left ventricular pacing leads will be randomized in a 1:1 ratio to have either an AV Delay and pacing chamber determined by SmartDelay™ or a Fixed AV Delay of 120 ms with biventricular pacing. Enrollment of an estimated 726 of subjects from up to 100 centers worldwide is planned to achieve 436 randomized subjects and 370 complete data sets required to power the primary endpoint. CONCLUSIONS: This trial will provide important data regarding the importance of AV Delay programming in patients with prolonged interventricular delay at the pacing sites.

Influence of patients' age at implantation on mortality and defibrillator shocks.

AIMS: Patients have increasing comorbidities and competing causes of death with advancing age, raising questions about the effectiveness of the implantable cardioverter defibrillators (ICD) in older age. We therefore investigated the effect of patients' age at initial device implantation on all-cause mortality and on the risk of ICD shocks in single-chamber (V-ICD), dual-chamber (D-ICD), and cardiac resynchronization therapy defibrillator (CRT-D) recipients. METHODS AND RESULTS: We reviewed de-identified records of 67 128 ICD recipients enrolled in the Boston Scientific ALTITUDE database of remote monitored patients [V-ICD (n = 11 422), D-ICD (n = 23 974), and CRT-D (n = 31 732)]. Over a mean follow-up of 2.3 ± 1.4 years, patients in all ICD groups had increased all-cause mortality but decreased risk of defibrillator shocks and/or anti-tachycardia pacing per 10 year increase in age. Compared with the youngest age group (<50 years), patients in the oldest age group (≥80 years) had a 6.8-fold, 5.9-fold, and 3.4-fold increase in all-cause mortality (P < 0.001 for all comparisons) and a 31, 45, and 53% decrease in the risk of ICD shock (P ≤ 0.002 for all comparisons) for the V-ICD, D-ICD, and CRT-D groups, respectively. CONCLUSION: Older recipients of standard and CRT defibrillators have higher mortality but fewer ICD shocks and/or therapies compared with younger patients. These data highly suggest less benefit of ICD therapy with increasing age, presumably because of competing risks of non-arrhythmic mortality. The role of defibrillator therapy in older patients may need to be evaluated with randomized controlled trials.

A Device Histogram-Based Simple Predictor of Mortality Risk in ICD and CRT-D Patients: The Heart Rate Score.

BACKGROUND: We hypothesized that survival in implantable cardioverter defibrillator (ICD) and cardiac resynchronization therapy defibrillator (CRT-D) patients is predicted by baseline Heart Rate Score. METHODS: Heart Rate Score is determined from the atrial paced and sensed histogram of a DDD ICD or CRT-D, and defined as percent of beats in the histogram in the tallest 10 beats/min range bin. It was calculated at initial remote monitoring for patients enrolled in LATITUDE® without persistent atrial fibrillation, and with pulse generators implanted in 2006-2011. Univariate, multivariate, and Kaplan-Meier analyses determined the impact of Heart Rate Score on survival. RESULTS: Of 57,893 ICDs and 67,929 CRT-Ds followed for 2.4 ± 1.5 years, each 10% increase in Heart Rate Score was associated with decreased survival (CRT-D hazard ratio [HR] 1.07 95%, confidence interval 1.06-1.07, P < 0.0001; ICD HR 1.05, 95% confidence interval 1.04-1.06, P < 0.0001). Multivariate analysis showed survival decreased with increasing age, atrial fibrillation, presence of a shock in first-year follow-up, and increasing programmed lower pacing rate in ICD and CRT-D patients. Increased percent right ventricular pacing predicted mortality in ICD patients, while male gender and lower percent left ventricular pacing predicted mortality in CRT patients. Heart Rate Score predicted survival independent of those variables. Heart Rate Score correlates with heart rate variability (standard deviation of average R-R intervals [SDANN]) when both are obtainable, but SDANN was only present in 6% of patients with Heart Rate Score >70%. CONCLUSION: A simple device histogram measure, Heart Rate Score, predicts survival in ICD and CRT-D patients independent of the available variables, and even when SDANN is unavailable.

Safety and effectiveness of a 6-French MRI conditional pacemaker lead: The INGEVITYTM clinical investigation study results.

BACKGROUND: The design of pacemaker leads has continued to evolve; ease of lead handling, improved electrical performance, and magnetic resonance imaging (MRI) conditional aspects have become more important, while safety remains critical. The INGEVITY™ family leads was designed to provide MRI conditional aspects, decreased diameter, and improved performance of pacemaker leads. The INGEVITY study is an investigational device exemption trial evaluating the acute and chronic safety and effectiveness of these leads. METHODS: Consecutive patients were included in 77 institutions worldwide, where 1,657 leads (846 right ventricular active fixation leads, 213 right ventricular passive fixation leads, 121 right atrial passive fixation preformed J-leads, and 477 right atrial active fixation leads) were implanted or attempted in 1,060 subjects. RESULTS: At 3-month follow-up, the electrical performance were: mean pacing threshold 0.67 V at 0.5-ms pulse width, pacing impedance 773 ohms, mean P-wave amplitude 4.8 mV, and R-wave amplitude 16.5 ± 6.5 mV. Over a median follow-up of 31 months, 93 subjects died and 33 subjects reported lead-related complications. Lead-related complication-free rate from 0 to 3 months and 3 to 12 months for all leads was 98.4% and 99.7%, respectively. The hazard of lead-related complications was observed to be decelerating over the course of follow-up (Weibull shape = 0.23). The overall lead dislodgment rate observed in the study was 1.3%, the perforation rate was 0.0%, and the pericardial effusion rate was 0.3%. CONCLUSIONS: The clinical performance of the INGEVITY lead demonstrated a high lead-related complication-free rate over 12 months of follow-up and excellent electrical characteristics.

The learning curve associated with the introduction of the subcutaneous implantable defibrillator.

AIMS: The subcutaneous implantable cardioverter defibrillator (S-ICD) was introduced to overcome complications related to transvenous leads. Adoption of the S-ICD requires implanters to learn a new implantation technique. The aim of this study was to assess the learning curve for S-ICD implanters with respect to implant-related complications, procedure time, and inappropriate shocks (IASs). METHODS AND RESULTS: In a pooled cohort from two clinical S-ICD databases, the IDE Trial and the EFFORTLESS Registry, complications, IASs at 180 days follow-up and implant procedure duration were assessed. Patients were grouped in quartiles based on experience of the implanter and Kaplan-Meier estimates of complication and IAS rates were calculated. A total of 882 patients implanted in 61 centres by 107 implanters with a median of 4 implants (IQR 1,8) were analysed. There were a total of 59 patients with complications and 48 patients with IAS. The complication rate decreased significantly from 9.8% in Quartile 1 (least experience) to 5.4% in Quartile 4 (most experience) (P = 0.02) and non-significantly for IAS from 7.9 to 4.8% (P = 0.10). Multivariable analysis demonstrated a hazard ratio of 0.78 (P = 0.045) for complications and 1.01 (P = 0.958) for IAS. Dual-zone programming increased with experience of the individual implanter (P < 0.001), which reduced IAS significantly in the multivariable model (HR 0.44, P = 0.01). Procedure time decreased from 75 to 65 min (P < 0.001). The complication rate and procedure time stabilized after Quartile 2 (>13 implants). CONCLUSION: There is a short and significant learning curve associated with physicians adopting the S-ICD. Performance stabilizes after 13 implants.

Chronic vagal stimulation for the treatment of low ejection fraction heart failure: results of the NEural Cardiac TherApy foR Heart Failure (NECTAR-HF) randomized controlled trial.

AIM: The neural cardiac therapy for heart failure (NECTAR-HF) was a randomized sham-controlled trial designed to evaluate whether a single dose of vagal nerve stimulation (VNS) would attenuate cardiac remodelling, improve cardiac function and increase exercise capacity in symptomatic heart failure patients with severe left ventricular (LV) systolic dysfunction despite guideline recommended medical therapy. METHODS: Patients were randomized in a 2 : 1 ratio to receive therapy (VNS ON) or control (VNS OFF) for a 6-month period. The primary endpoint was the change in LV end systolic diameter (LVESD) at 6 months for control vs. therapy, with secondary endpoints of other echocardiography measurements, exercise capacity, quality-of-life assessments, 24-h Holter, and circulating biomarkers. RESULTS: Of the 96 implanted patients, 87 had paired datasets for the primary endpoint. Change in LVESD from baseline to 6 months was -0.04 ± 0.25 cm in the therapy group compared with -0.08 ± 0.32 cm in the control group (P = 0.60). Additional echocardiographic parameters of LV end diastolic dimension, LV end systolic volume, left ventricular end diastolic volume, LV ejection fraction, peak V02, and N-terminal pro-hormone brain natriuretic peptide failed to show superiority compared to the control group. However, there were statistically significant improvements in quality of life for the Minnesota Living with Heart Failure Questionnaire (P = 0.049), New York Heart Association class (P = 0.032), and the SF-36 Physical Component (P = 0.016) in the therapy group. CONCLUSION: Vagal nerve stimulation as delivered in the NECTAR-HF trial failed to demonstrate a significant effect on primary and secondary endpoint measures of cardiac remodelling and functional capacity in symptomatic heart failure patients, but quality-of-life measures showed significant improvement.

The effect of left ventricular electrical delay on the acute hemodynamic response with cardiac resynchronization therapy.

INTRODUCTION: Cardiac resynchronization therapy (CRT) improves hemodynamic function, as well as reduces hospitalizations and mortality among patients with systolic dysfunction, QRS prolongation, and heart failure. The magnitude of the hemodynamic response is associated with improved outcomes, so optimization of this parameter is a goal of therapy. The purpose of this study was to evaluate the effect of left ventricular (LV) electrical delay, as assessed by the QLV interval, on the acute hemodynamic response to CRT. METHODS AND RESULTS: This study included 31 patients undergoing biventricular ICD placement. At implant, invasive LV dP/dt was measured by a micromanometer catheter during biventricular (BV) or LV only pacing. Both atrial sensing (AS) and atrial pacing (AP) modes were evaluated at 5 different AV delays, tested in randomized order. The QLV interval was measured at the LV pacing site. Compared with intrinsic rhythm, CRT increased LV dP/dtmax by 9.5 ± 8.8% with BV pacing and 10.0 ± 9.2% with LV pacing (P = 0.38) during AS. With AP, CRT increased LV dP/dtmax by 16.0 ± 10.8% and 15.3 ± 11.1%, respectively (P = 0.47). QLV was strongly correlated with the hemodynamic response in all pacing configurations. Multivariate analysis showed that with BV pacing QLV was an independent predictor of the hemodynamic response with a 1.7% increase in %LV dP/dt for every 10 milliseconds prolongation of QLV. CONCLUSIONS: LV electrical delay is a strong predictor of the acute hemodynamic response to CRT. This relationship is independent of pacing mode.

Atrioventricular optimization improves cardiac resynchronization response in patients with long interventricular electrical delays: A pooled analysis of the SMART-AV and SMART-CRT trials.

BACKGROUND: The utility of atrioventricular (AV) optimization (AVO) algorithms remains in question. A substudy of the SMART-AV trial found that patients with prolonged interventricular delays ≥70 ms were more likely to benefit from cardiac resynchronization therapy (CRT) with AVO. The SMART-CRT trial evaluated AVO on the basis of these results, but the study was underpowered. OBJECTIVE: To increase statistical power, data from SMART-AV patients meeting the inclusion criterion of interventricular delay ≥70 ms were pooled with data from SMART-CRT to reassess AVO. METHODS: SMART-CRT and SMART-AV were prospective, randomized, multicenter clinical trials. Patients in both studies were randomized to be programmed with an AVO algorithm (SmartDelay) or fixed AV delay (120 ms). Paired echocardiograms obtained at baseline and 6 months were compared, with CRT response defined as ≥15% reduction in left ventricular end-systolic volume. RESULTS: A total of 451 complete patient data sets were pooled and analyzed. The baseline demographics between studies did not differ statistically in terms of age, sex, left ventricular ejection fraction, or left ventricular end-systolic volume. The AVO group had a greater proportion of CRT responders (SmartDelay, 73.9%; fixed, 63.1%; P = .014) and greater changes in measures of reverse remodeling. SmartDelay patients with a recommended sensed AV delay outside the nominal range (100-120 ms) had 2.3 greater odds of CRT response than fixed AV delay patients. CONCLUSION: Greater CRT response and measures of reverse remodeling were observed in patients with SmartDelay enabled vs a fixed AV delay. This study supports the use of SmartDelay in patients with a CRT indication and interventricular delay ≥70 ms. GOV REGISTRATION: NCT00677014 and NCT03089281.

High initial heart rate score is an independent predictor of new atrial high-rate episodes in pacemaker patients with sinus node dysfunction.

BACKGROUND: Heart rate score (HRSc), the percentage of atrial depolarizations in the largest paced and sensed 10-beats/min histogram bin recorded in cardiac devices, is associated with several adverse outcomes, but it remains uncertain whether HRSc independently predicts atrial high-rate episodes (AHREs) in patients with sinus node dysfunction (SND) undergoing pacemaker (PM) implantation. OBJECTIVE: This study aimed to determine whether initial HRSc after PM implantation predicts new-onset AHREs in patients with SND. METHODS: Patients had Boston Scientific PMs implanted for SND from 2012 to 2021 at Cleveland Clinic, University of Occupational and Environmental Health, Japan, Kyushu Rosai Hospital, and JCHO Kyushu Hospital. Patients were excluded if they had atrial fibrillation before PM implantation or AHREs within 3 months after implantation. Subsequent AHREs after implantation were evaluated and correlated with HRSc. RESULTS: During 48.9 (interquartile range, 25.7-50.4) months, 130 consecutive PM patients (76 ± 10 years; 40% male) had a median initial HRSc of 74% (57%-86%). AHREs defined by >1%, >6 h/d burden, and atrial tachycardia response events >24 hours developed in 27 of 130 (21%), 15 of 130 (12%), and 9 of 130 (7%), respectively. For each definition, patients with HRSc ≥80% had higher occurrence of AHREs than those with HRSc <80% (both P = .008, log-rank test). After adjustment for age, race, comorbidities, left ventricular ejection fraction, left atrial diameter, and cumulative percentage of right atrial and right ventricular pacing, initial HRSc ≥80% (hazard ratio, 3.33; 95% CI, 1.35-8.18; P = .009) and male sex (hazard ratio, 2.59; 95% CI, 1.06-6.33; P = .04) independently predicted AHREs. CONCLUSION: HRSc ≥80% is associated with new-onset, device-determined AHREs for patients undergoing PM implantation for SND. HRSc may have prognostic and therapeutic implications.

Effects of Atrioventricular Optimization on Left Ventricular Reverse Remodeling With Cardiac Resynchronization Therapy: Results of the SMART-CRT Trial.

BACKGROUND: The role of atrioventricular optimization (AVO) to improve cardiac resynchronization therapy outcomes remains controversial. Previous post hoc analyses of a multicenter trial showed that measures of electrical dyssynchrony (right ventricular-left ventricular [LV] or LV electrical delay durations) are associated with patients who benefit from AVO. METHODS: This was a global, multicenter, prospective, randomized trial of de novo cardiac resynchronization therapy implant patients with an right ventricular-LV duration ≥70 ms to determine whether AVO results in greater reverse remodeling. Patients were randomized 1:1 for either an AVO algorithm (SmartDelay) that determines atrioventricular delay and pacing chamber, biventricular or LV only, or a fixed atrioventricular delay of 120 ms with biventricular pacing. Paired echocardiograms performed at baseline and 6 months were evaluated. The primary end point was echocardiographic cardiac resynchronization therapy response, defined dichotomously as a >15% reduction in LV end-systolic volume. RESULTS: A total of 310 patients (n=120 women) were randomized and had completed 6 months of follow-up. The echocardiographic cardiac resynchronization therapy response rate did not statistically differ between the groups (SmartDelay, 74.8%; fixed, 67.7%; P=0.17). Analyses of prespecified secondary end points demonstrated significant improvements in the absolute (median: SmartDelay, -41.0 mL; fixed, -33.0 mL; P=0.01) and relative change in LV end-systolic volume (SmartDelay, -38.3%; fixed, -27.8%; P=0.03) for patients with SmartDelay optimization. Similar results were observed for the relative improvement in LV ejection fraction (SmartDelay, 46.7%; fixed, 32.1%; P=0.050); absolute improvement in LV ejection fraction trended to be higher with SmartDelay (P=0.06). CONCLUSIONS: Analysis of reverse remodeling parameters demonstrated that AVO via SmartDelay, relative to the nonoptimized fixed atrioventricular delay comparator group, improved absolute and relative changes in LV function in patients with longer right ventricular-LV duration. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03089281.

Heart rate score, a measure related to chronotropic incompetence in pacemaker patients.

BACKGROUND: Heart rate score (HrSc) ≥70% in cardiac resynchronization therapy defibrillator and implantable cardioverter-defibrillator subjects predicts 5-year mortality risk. A high HrSc suggests few sensed cardiac cycles above the programmed lower rate. OBJECTIVE: To determine if HrSc is related to chronotropic incompetence (CI) in pacemaker (PM) subjects. METHODS: HrSc is the percentage of all atrial-paced and sensed events in the single tallest 10 beats/min histogram bin programmed to DDD 60/min. The prospective LIFE study of PM subjects examined multiple treadmill-based measures of CI. The 1-month postimplant DDD 60/min PM rate histogram prior to treadmill was retrospectively analyzed for HrSc. Measures of CI were applied to submaximal treadmill data in the DDD mode. HrSc was compared to these CI measures and to clinical indications for PM. RESULTS: The 1-month histogram demonstrated HrSc ≥70% in 43% of subjects. HrSc ≥70% correlated with a clinical diagnosis of sick sinus syndrome (P < .001). CI was present in 34%-88% of subjects by treadmill-based measures. Agreement between treadmill-based measures for CI was poor and varied from 39% to 83%. HrSc ≥70%, as a measure of CI, was most highly correlated with unpaced heart rate <70% of age-predicted maximum heart rate (67%) (odds ratio 3.7, P < .001). CONCLUSIONS: HrSc ≥70% correlates with treadmill measures of CI and clinical sick sinus syndrome. HrSc ≥70% is a measure of CI in PM subjects that is inexpensive, repeatable, and quantitative.

Lower rate limit for pacing by cardiac resynchronization defibrillators: Should lower rate programming be reconsidered?

BACKGROUND: No real-world large database associates lower rate limit (LRL) programming and survival of subjects with cardiac resynchronization therapy-defibrillators (CRT-Ds). OBJECTIVE: The purpose of this study was to test the hypothesis that lower LRL programming is independently associated with survival, and that LRL and heart rate score (HrSc) are associated. METHODS: All dual-chamber CRT-D devices in the Remote Patient Monitoring (RPM) ALTITUDE database (2006-2011) were queried. Baseline HrSc was defined as the percentage of all atrial sensed and paced beats in the tallest 10-beat histogram bin postimplant. LRL was assessed during repeated RPM uploads. Using a Cox model multivariable analysis, relationships between LRL, survival, HrSc, and other variables were evaluated. Survival was determined by query of death indices. RESULTS: Data analyzed included 61,881 subjects (mean follow-up 2.9 years). LRL ranged from 40 to 85 bpm. Baseline lower LRL was associated with younger age, less atrial fibrillation, female sex, and lower HrSc (P <.001 for all covariates). Lower LRL was associated with improved survival, with LRL 40 associated with the largest survival benefit. This was significant for all 3 HrSc subgroups (P <.001). An interaction between HrSc and LRL was observed, with the largest survival difference between HrSc groups observed at LRL-40 (P <.001). CONCLUSION: LRL programming and HrSc were associated, and lower values of both were associated with improved survival in a large database of CRT-D subjects. Relationships between survival, LRL programming, and HrSc merit further study.

Assessment of primary prevention patients receiving an ICD - Systematic evaluation of ATP: APPRAISE ATP.

BACKGROUND: The value of antitachycardia pacing (ATP) in the overall cohort of primary prevention patients who receive implantable cardioverter-defibrillators (ICDs) remains uncertain. ATP success reported in prior trials potentially included a large number of patients receiving unnecessary ATP for arrhythmias that may have self-terminated owing to the prematurity of the intervention. Although some patients derive benefit from initial ATP in terminating rapid ventricular arrhythmias and thereby preventing shocks, there are limited data allowing us to identify those patients a priori. OBJECTIVE: The purpose of APPRAISE ATP is to understand the role of ATP in primary prevention patients currently indicated for ICD therapy in a large prospective randomized controlled trial with modern programming parameters. METHODS: The study is a global, prospective, randomized, multicenter clinical trial conducted at up to 150 sites globally, enrolling approximately 2600 subjects The primary endpoint of the trial is time to first all-cause shock in a 2-arm study with an equivalent study design in which the incidence of all-cause shocks will be compared between primary prevention subjects programmed with shocks only vs subjects programmed to standard therapy (ATP and shock). RESULTS: An Electrogram and Device Interrogation Core Laboratory will review interrogation data to determine primary endpoints that occur in APPRAISE ATP. Their decisions are based on independent physician review of the data from device interrogation. CONCLUSION: The ultimate purpose of the study is to aid clinicians in the selection of ICD technologies based on hard endpoint evidence across the spectrum of indications for primary prevention implantation.

Comparison of measures of ventricular delay on cardiac resynchronization therapy response.

BACKGROUND: Left ventricular (LV) pacing at sites of prolonged LV delay (QLV) or at long interventricular delay (right ventricle [RV]-LV) is strongly associated with cardiac resynchronization therapy (CRT) response. QLV and RV-LV have been independently evaluated, but little is known regarding the interrelationship between these measures or of delay to the RV. OBJECTIVE: The purpose of this study was to evaluate the relationship between measures of electrical delay on CRT response in the SMART-AV (SmartDelay Determined AV Optimization: A Comparison to Other AV Delay Methods Used in Cardiac Resynchronization Therapy) trial. METHODS: In 419 patients, QLV and RV-LV were measured. CRT response was defined as a >15% reduction in LV end-systolic volume from implant to 6 months. The correlation between QLV and RV-LV and the clinical variables associated with the difference between QLV and RV-LV (QRV) were determined. Multivariable logistic regression was used to analyze the association between these measures on CRT response. A machine learning algorithm was used to construct a classification tree to predict response to CRT. RESULTS: The cohort was 66% male (age 66 ± 11 years), 75% had left bundle branch block; and QRS was 150 ± 25 ms. QLV and RV-LV were highly correlated (R2 = 0.71). A longer QRV was observed among patients with right bundle branch block, ischemic cardiomyopathy, and increased QRS. In a multivariable model including QLV, RV-LV, and other known predictors of CRT response, RV-LV, but not QLV, remained associated with CRT response (odds ratio 1.13; 95% confidence interval 1.02-1.26; P = .017). Combining the 2 measures achieved better prediction of CRT response in the group with intermediate RV-LV. CONCLUSION: RV-LV is a better predictor of CRT response than QLV. There is incremental value in using both measurements or QRV in certain subpopulations.

How Well Do Results From Randomized Clinical Trials and/or Recommendations for Implantable Cardioverter-Defibrillator Programming Diffuse Into Clinical Practice?Translation Assessed in a National Cohort of Patients With Implantable Cardioverter-Defibrillators ( ALTITUDE ).

Background Inappropriate implantable cardioverter-defibrillator programming can be detrimental. Whether trials/recommendations informing best implantable cardioverter-defibrillator programming (high-rate cutoff and/or extended duration of detection) influence practice is unknown. Methods and Results We measured reaction to publication of MADIT-RIT (Multicenter Automatic Defibrillator Implantation Trial-Reduce Inappropriate Therapy; 2012) and the Consensus Statement (2015) providing generic programming parameters, in a national cohort of implantable cardioverter-defibrillator recipients, using the ALTITUDE database (Boston Scientific). Yearly changes in programmed parameters to either trial-specified or class 1 recommended parameters (≥185 beats per minute or delay ≥6 seconds) were assessed in parallel. From 2008 to 2017, 232 982 patients (aged 67±13 years; 28% women) were analyzed. Prevalence of MADIT- RIT -specific settings before publication was <1%, increasing to 13.6% in the year following. Thereafter, this increased by <6% over 5 years. Among preexisting implants (91 171), most patients (58 739 [64.4%]) underwent at least 1 in-person device reprogramming after trial publication, but <2% were reprogrammed to MADIT - RIT settings. Notably, prevalence of programming to ≥185 beats per minute or delay ≥6 seconds was increased by MADIT - RIT (57.4% in 2013 versus 40.2% at baseline), but the following publication of recommendations had minor incremental effect (73.2% in 2016 versus 70.8% in 2015). High-rate cutoff programming was favored almost 2-fold compared with extended duration throughout the test period. Practice changes demonstrated large interhospital and interstate variations. Conclusions Trial publication had an immediate effect during 1 year postpublication, but absolute penetration was low, and amplified little with time. Consensus recommendations had a negligible effect. However, generic programming was exercised more widely, and increased after trial publication, but not following recommendations.

Development of a biomarker panel to predict cardiac resynchronization therapy response: Results from the SMART-AV trial.

BACKGROUND: Predicting a favorable cardiac resynchronization therapy (CRT) response holds great clinical importance. OBJECTIVE: The purpose of this study was to examine proteins from broad biological pathways and develop a prediction tool for response to CRT. METHODS: Plasma was collected from patients before CRT (SMART-AV [SmartDelay Determined AV Optimization: A Comparison to Other AV Delay Methods Used in Cardiac Resynchronization Therapy] trial). A CRT response was prespecified as a ≥15-mL reduction in left ventricular end-systolic volume at 6 months, which resulted in a binary CRT response (responders 52%, nonresponders 48%; n = 758). RESULTS: Candidate proteins (n = 74) were evaluated from the inflammatory, signaling, and structural domains, which yielded 12 candidate biomarkers, but only a subset of these demonstrated predictive value for CRT response: soluble suppressor of tumorgenicity-2, soluble tumor necrosis factor receptor-II, matrix metalloproteinase-2, and C-reactive protein. These biomarkers were used in a composite categorical scoring algorithm (Biomarker CRT Score), which identified patients with a high/low probability of a response to CRT (P <.001) when adjusted for a number of clinical covariates. For example, a Biomarker CRT Score of 0 yielded 5 times higher odds of a response to CRT compared to a Biomarker CRT Score of 4 (P <.001). The Biomarker CRT Score demonstrated additive predictive value when considered against a composite of clinical variables. CONCLUSION: These unique findings demonstrate that developing a biomarker panel for predicting individual response to CRT is feasible and holds potential for point-of-care testing and integration into evaluation algorithms for patients presenting for CRT.

Mild-to-moderate symptoms during the first year of antiretroviral therapy worsen quality of life in HIV-infected individuals.

Symptoms and quality of life were assessed among human immunodeficiency virus (HIV)-infected individuals initiating their first course of antiretroviral therapy. Symptoms, which were mostly mild or moderate, were common in the first year and significantly affected the patients' quality of life. Quality of life was inversely related to the number of symptoms and in the change in the number of symptoms from baseline.

Addition of minute ventilation to rate-response pacing improves heart rate score more than accelerometer alone.

BACKGROUND: Heart rate score (HRSc) ≥70%, a novel parameter, predicts risk of mortality in patients with implantable cardioverter-defibrillators and identifies patients who have survival benefit with DDDR vs DDD pacing. OBJECTIVE: The purpose of this study was to determine if DDDR pacing lowers HRSc, and a blended sensor with minute ventilation (MV) and accelerometer (XL) improves HRSc more than accelerometer (XL) alone in patients requiring pacemakers (PMs). METHODS: HRSc, the percentage of all beats in the tallest 10-beat/min device histogram bin, was calculated. Data from the Limiting Chronotropic Incompetence for Pacemaker Recipients Study, a prospective randomized trial of PM patients, comparing XL to blended-sensor (XL + MV) rate-responsive pacing, were analyzed retrospectively for HRSc changes from baseline. The relationship of patient activity (sensor-detected from device memory) to HRSc was examined. RESULTS: Of the 501 randomized patients, 215 (43%) patients had HRSc ≥70% during DDD pacing at baseline. In these patients, HRSc decreased after DDDR programming by 14.2%, while it increased by 0.4% in those with baseline HRSc <70% (n = 286) (HRSc ≥70% vs HRSc <70%; P < .01). No differences were detected between the 2 randomized sensor-based groups at baseline. Blended-sensor (MV + XL) programming reduced HRSc more than the XL sensor alone (MV + XL: 18% vs XL: 10%; P < .001). No correlation was observed between patient activity and HRSc (correlation = -0.14; P = .07). CONCLUSION: HRSc improved (reduced) with rate-response (DDDR) programming in PM patients with high HRSc during DDD pacing. Blended sensors (MV + XL) improved HRSc more than XL alone. HRSc does not correlate with patient activity levels, suggesting that other patient factors determine this parameter. This programming approach needs to be investigated prospectively in a PM outcomes trial.