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Programming Implantable Cardioverter Defibrillator in Primary Prevention: Guideline Concordance and Outcomes
Journal Pre-proof Programming Implantable Cardioverter Defibrillator in Primary Prevention: Guideline Concordance and Outcomes Teetouch Ananwattanasuk, MD, Tanyanan Tanawuttiwat, MD, MPH, Ronpichai Chokesuwattanaskul, MD, Sangeeta Lathkar-Pradhan, MBBS, Waseem Barham, MD, Hakan Oral, MD, FHRS, Ranjan K. Thakur, MD, MPH, MBA, Krit Jongnarangsin, MD PII:
S1547-5271(20)30093-X
DOI:
https://doi.org/10.1016/j.hrthm.2020.02.004
Reference:
HRTHM 8274
To appear in:
Heart Rhythm
Received Date: 16 December 2019 Accepted Date: 1 February 2020
Please cite this article as: Ananwattanasuk T, Tanawuttiwat T, Chokesuwattanaskul R, Lathkar-Pradhan S, Barham W, Oral H, Thakur RK, Jongnarangsin K, Programming Implantable Cardioverter Defibrillator in Primary Prevention: Guideline Concordance and Outcomes, Heart Rhythm (2020), doi: https:// doi.org/10.1016/j.hrthm.2020.02.004. This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. © 2020 Published by Elsevier Inc. on behalf of Heart Rhythm Society.
Programming Implantable Cardioverter Defibrillator in Primary Prevention: Guideline Concordance and Outcomes
Running Title: Ananwattanasuk et al.; Guideline concordance and outcomes in ICD programming
Teetouch Ananwattanasuk, MDa,b; Tanyanan Tanawuttiwat, MD, MPHc; Ronpichai Chokesuwattanaskul, MDa; Sangeeta Lathkar-Pradhan, MBBSa; Waseem Barham, MDd, Hakan Oral, MD, FHRSa; Ranjan K. Thakur, MD, MPH, MBAd; Krit Jongnarangsin, MDa
a
Cardiac Electrophysiology, University of Michigan Health System, Ann Arbor, Michigan; Cardiology Division, Department of Internal Medicine, Vajira Hospital, Navamindradhiraj University, Thailand; cDivision of Cardiology, Department of Medicine, University of Mississippi Medical Center, Jackson, Mississippi; dCardiac Electrophysiology, Michigan State University and Sparrow Thoracic and Cardiovascular Institute, Lansing, Michigan b
Funding: None Address for Correspondence: Krit Jongnarangsin, MD Cardiac Electrophysiology, University of Michigan Health System, 1500 E Medical Center Dr SPC 5856, Ann Arbor, MI 48109-5856 Email: [email protected] Disclosures: None. Acknowledgments: None. *A portion of the results were presented at the 2018 AHA Scientific Sessions
Word Count: 4190
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Abstract Background: Inappropriate therapy is a common adverse effect in patients with implantable cardioverter defibrillator (ICD) that may be prevented by appropriate programming. Objectives: The study aims to assess outcomes of the device programming based on a 2015 HRS/EHRA/APHRS/SOLAECE expert consensus statement and a 2019 focused update on optimal implantable cardioverter-defibrillator programming and testing. Methods: Consecutive patients who underwent ICD for primary prevention during 2014-2016 at 3 centers were included in the retrospective analysis. The patients were classified into 2 groups based on the tachycardia programming at the time of implant: guideline concordant group (GC) and non-guideline concordant group (NGC). Kaplan-Meier analysis and Cox proportional hazard models were used to estimate freedom from ICD therapy (ATP or shock), ICD shock and death. Results: A total of 772 patients were included in the study (mean age 63.3 ± 13.8 years). Of this total, 258 patients (33.4%) were in GC group and 514 patients (66.6%) were in NGC group. During the mean follow up of 2.02 ± 0.91 years, guideline concordant programming was associated with a 53% reduction in ICD therapy (p < 0.01) and 50% reduction in ICD shock (p 0.02). There were no significant differences in mortality (6% in GC group vs.11% in NGC group, p 0.22). Conclusion: Only 1/3 of the studied population had ICD device programmed in concordance with the current guidelines. ICD programming based on the current guidelines was associated with a significantly lower rate of ICD therapy and shock without changes in mortality during intermediate-term follow up.
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Keywords: Implantable Cardioverter Defibrillator, ICD programming guideline, ICD shock, ICD therapy, Primary prevention
Introduction The implantable cardioverter defibrillator (ICD), either alone or in conjunction with cardiac resynchronization therapy (CRT) is highly effective in reducing mortality among patients at risk for fatal arrhythmias. As such, ICD implantation has long become the standard of cardiovascular care in appropriate patients based on detailed guidelines and backed by a board literature base (1-5). However, there are accumulated evidence that non-essential ICD therapies, particularly for non-sustained ventricular tachycardia (VT), and inappropriate shocks for supraventricular tachyarrhythmias (SVTs), atrial fibrillation, and noise affect up to 8-40% of patients and may actually increase morbidity and mortality (6-9). Several randomized trials and prospective studies have examined the effect of ICD programming designed to reduce inappropriate shocks by increasing both detection duration and detection heart rates (7, 10-15). Furthermore, manufacturer technological improvements have aimed at reducing unnecessary ICD therapy by improving discriminators of SVTs and algorithms designed to reduce oversensing. In a meta-analysis encompassing a total of 7687 patients, ICD therapy reduction strategy resulted in a 30% decrease in all-cause mortality when compared to conventional programming (16). This mortality decrease can largely be attributed to a 50% reduction in inappropriate shocks. However, 1 death may have been related to ICD therapy reduction programming (13). This may hint towards the possible trade-off between ICD therapy 3
reduction programming strategies and failure to treat episodes of VT or ventricular fibrillation (VF) and may reflect less controlled settings outside of study protocols. HRS/EHRA/APHRS/SOLAECE issued an expert consensus statement on optimal implantable cardioverter-defibrillator programming and testing in 2015(17) as well as a focused update in 2019(18), based on the current evidence from clinical trials. The current study aims to 1) evaluate the real-world ICD programming among patients with an ICD implant for primary prevention and its concordance with the 2015 HRS/EHRA/APHRS/SOLAECE expert consensus statement as well as the 2019 focused update on optimal implantable cardioverter-defibrillator programming and testing and 2) compare the occurrence of the ICD therapies and mortality in patients who have ICD parameters programmed following the guidelines and those who have the ICD programmed outside the guidelines. Methods Study Population Consecutive adult patients who underwent initial transvenous ICDs or CRT-Ds implant for primary prevention indication (5) at 3 tertiary care hospitals, including University of Michigan, Michigan State University, and University of Mississippi Medical Center, from January 2014 to December 2016 were included. Patients who had a follow up duration of less than 3 months or missing initial ICD programming parameter data were excluded from the study. Databases from 3 centers were reviewed and collated in a blinded fashion for review by the investigators. The present study was approved by the institutional review boards for each of the participating centers. Data collection and Definitions
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Data collection was performed by reviewing medical records for baseline characteristics, implantation data and follow-up data on clinical outcomes, therapy delivery, and death. The patient was categorized according to whether the device programming followed the 2015 HRS/EHRA/APHRS/SOLAECE expert consensus statement (Appendix B Manufacturer Specific Translation of ICD Programming Recommendations) and the 2019 focused update on optimal implantable cardioverter-defibrillator programming and testing. The guideline concordant group (GC) was defined as patients who had ICD programming following the guideline recommendations at the time of implant, with all of the following criteria: 1)
Tachyarrhythmia detection duration criteria was programmed to allow the tachycardia to continue for at least 6 seconds or for 30 intervals before completing detection. A detection duration of 2.5 seconds is allowed for detection rate ≥250 bpm (high-rate therapy option) and a detection interval of 24 is allowed if a 30interval delay is not programmable.
2)
The slowest tachycardia therapy zone limit show was programmed between 185 and 200 bpm.
3)
The discrimination algorithms to distinguish SVT from VT was programmed on unless complete heart block was present.
4)
ATP therapy was programmed on for all ventricular tachyarrhythmia detection zones with available ATP therapy.
The non-guideline concordant group (NGC) was defined as patients who had ICD programming that differed from the guideline recommendations
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Statistical Analysis Categorical variables were presented as numbers and percentages and were compared for the entire cohort using Chi-square test and Fisher’s exact test as appropriate. The continuous variables are presented as mean ± SD and compared using the Student t-test or Mann-Whitney U-test. In the primary analysis, a Cox proportional hazards regression model was used to estimate the risk of a first occurrence of any therapy, shock, and all-cause mortality. Cox model variables with a p-value < 0.10 were considered to have actually interfered with the survival of the patients. A p-value of 0.05 was deemed to be statistically significant. We constructed Kaplan-Meier graphs for the primary and secondary endpoints with a log-rank test for significant testing. Crude rates of first therapy, first shock, and death were compared with the use of Chisquare tests. All statistics will be analyzed by Stata, version 15.0 (Stata Corp LP, College Station, TX) and SPSS 23.0 software (SPSS Inc., Chicago, IL, USA). Results Study Population A total of 831 patients were reviewed and 59 patients were excluded from the study due to the lack of initial programming data or insufficient follow-up time. The baseline clinical characteristics of patients are presented in Table 1. The mean age was 63.3 ± 13.8 years and 66.1 % of patients were male. Of the 772 included patients, 258 patients (33.4%) were in GC group and 514 patients (66.6%) in NGC group. The mean follow up duration was 2.0 ± 0.9 years. Baseline characteristics ofNCG group were comparable to GC group except for significantly older age (64.8 ± 13.7 vs 60.3 ± 13.5, p value < 0.01), longer follow up duration (2.1+0.92 years
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vs 1.9+0.9 years, p value < 0.01), lower rate of antiplatelet used (53.9% vs 66.3%, p value < 0.01), and lower rate of ARBs used (18.5% vs 25.2%, p value 0.03). The type and distribution of device manufacturers was significantly different in both groups (p value 0.02 and p value < 0.01, respectively). Devices were programmed in concordance with the guideline in 6 of 45 (13.3%) Biotronik devices, 112 of 349 (32.1%) Boston Scientific devices, 140 of 222 (63.6%) Medtronic devices, and 0 of 156 St. Jude Medical devices (Table 2). ICD Therapies and Mortality Among the 772 patients, 137 patients (17.7%) received ICD therapy (ATP or shock), 78 patients (10.1%) received ICD shock, and 54 patients (7.0%) died (Table 3). Univariate analysis showed that the risk of ICD therapy was significantly lower in GC group (HR: 0.49, 95% CI: 0.32 – 0.75, p<0.01), female (HR: 0.62, 95% CI: 0.42 – 0.91, p 0.01) and those with diabetes (HR: 0.69, 95% CI: 0.47 – 0.99, p 0.04). The risk of ICD shock was also significantly lower in GC group (HR: 0.58, 95% CI: 0.34 – 0.99, p 0.04), female (HR: 0.43, 95% CI: 0.25 – 0.76, p<0.01) and those who had PCI (HR: 0.52, 95% CI: 0.28 – 0.97, p 0.04). Among device manufacturers comparing to Boston Scientific, Medtronic devices had a lower rate of ICD therapy (HR: 0.62, 95% CI: 0.40 – 0.95, p 0.03). Multivariate Cox regression analysis (Table 4) showed that Guideline concordant ICD programming was associated with a 53% reduction in any ICD therapy (HR: 0.47, 95% CI: 0.29 - 0.75, p<0.01) and a 50% reduction in ICD shock (HR: 0.50, 95% CI: 0.27-0.91, p 0.02). The risk of ICD therapy and ICD shock were reduced by 38% (HR: 0.62, 95% CI: 0.42 – 0.91, p 0.02) and 61% (HR: 0.39, 95% CI: 0.22 – 0.68, p<0.01), respectively in females. History of paroxysmal supraventricular tachycardia was associated with a higher risk of ICD therapy (HR: 2.05, 95% CI: 1.09 – 3.86, p 0.03). However, device 7
manufacturer was not found to be an independent predictor for either ICD therapy or ICD shock. Kaplan-Meier survival curve (Figure 1) showed a significantly lower estimated 3-year incidence of ICD therapy (13% vs. 29%, p < 0.01) and ICD shock (7% vs. 17%, p 0.04) in GC group. There was no significant difference in mortality at 3 years between GC and NGC groups (6% vs. 11%, p 0.22). Discussion The present study shows that tachycardia detection in the majority of patients who underwent ICD/CRT-D implant for primary prevention was not programmed as recommended by the current guidelines (18). Default ICD setting in each manufacturer might be an important factor that affects the compliance with the guideline. Among all manufacturers, patients with Medtronic devices had the highest proportion of guideline concordant ICD programming. Default tachycardia detection of Medtronic devices is similar to the programming in the previous trials (10, 19) and the current guidelines which requires no programming changes at the implant. ICD settings recommended in the guidelines were developed based upon prior studies including algorithms for discrimination of supraventricular tachycardia, prolonged duration of arrhythmia detection, faster rates for tachycardia detection, and anti-tachycardia pacing (13, 14, 2021)
. The overriding principle is to be certain that there is a sustained tachyarrhythmia before
treating the rhythm and that the treated rhythm is ventricular arrhythmias, not supraventricular arrhythmias. Our study demonstrated that programming ICD therapies following the guideline statement was associated with reductions in ICD therapy and shock without changes in mortality during intermediate-term follow up. The reduction of ICD therapy was due to both decreases in inappropriate therapies and avoidable therapies. The reduction in inappropriate therapies is most likely from SVT discrimination function recommended by the current guidelines. MADIT-RIT 8
showed that the majority of the inappropriate therapies from atrial arrhythmia occurred in the range of 170-199 bpm and that the ample majority of those arrhythmias were caused by regular supraventricular arrhythmia, resulting in failure of traditional device algorithms such as sudden onset, stability, and atrioventricular relationship to discriminate between atrial and ventricular tachyarrhythmias in this range (22). Inappropriate therapies delivered for rhythm above 200 bpm were less prevalent and were more frequently caused by atrial fibrillation, atrial flutter or oversensing. At this rapid rate, the prolonged duration of arrhythmia detection was the only effective strategy that significantly reduced inappropriate therapies (22). There are some concerns about safety and the potential risks from delay therapy, syncope or failure to detect when the device is programmed with high detection rates and prolonged arrhythmia detection. MADIT-RIT trial showed that ICD programming with therapy for ventricular tachycardia ≥200 bpm or a long delay is not associated with increased risk of arrhythmogenic or all-cause syncope, and syncope caused by slow ventricular tachycardias (<200 bpm) is a rare event (23). Nonetheless, the recent case series by Thogersen AM et al. raised this concern. The investigators reported that no patient with manufacturer-specific programming validated in clinical trials failed to receive an initial, timely shock for ventricular fibrillation. However, most of the studied patients who did not receive timely ventricular fibrillation shocks had ICDs programmed according to guidelines extrapolated from evidence obtained by using another manufacturer’s ICDs with different sensing and detection features. The study concluded that complex and unanticipated interactions between manufacturer-specific features and generic programming can prevent therapy for VF. More data are needed to assess the risks and benefits of translating evidence-based detection parameters from one manufacturer to another (24). Study limitations 9
The study is a non-randomized retrospective study with a limited number of participants. The decision of the device programming was not randomized and was based on physician’s discretion. Therefore, there is a high heterogeneity of patient selections and device programming in the NGC group. these factors potentially have effects on the outcomes of the study. Due to the possibility of device programming changes after the first therapy and possible impact to the outcome from the changes, the following therapies were not evaluated. The limitation in evaluating only the first occurrence of therapy may not reflect the long-term outcomes of guideline-based programming. As previously mention, there are some possible effects from the manufacturer specific algorithm for managing ventricular arrhythmias and SVT discrimination. The data on the follow-up echocardiogram is not available. The patients with CRT-D device were included in the study and were accounted for 38.7% of studied populations. The improved LVEF may affect the occurrence of ICD therapy. The number of events and deaths in the withinguideline group in this study is small and may have limited power. The adjudications of the therapies whether they were appropriate were not done due to the potential inaccuracy in patients with single-chamber ICD. However, the GC group was associated with a significantly lower rate of ICD therapy and shock without changes in mortality. For the generalizability, this study is limited to patients with primary prevention ICD indication and the results cannot be applied to those with secondary prevention ICD indications. Conclusion Only one third of the studied population had devices programmed as recommended by 2015 HRS/EHRA/APHRS/SOLAECE expert consensus statement and 2019 focused update on optimal implantable cardioverter-defibrillator programming and testing. Programming ICD
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therapies following the guideline statement was associated with reductions in ICD therapy and shock without changes in mortality during intermediate-term follow up. Reference 1. Moss AJ, Hall WJ, Cannom DS, et al. Improved survival with an implanted defibrillator in patients with coronary disease at high risk for ventricular arrhythmia. Multicenter Automatic Defibrillator Implantation Trial Investigators. N Engl J Med. 1996;335(26):1933-40. 2. Moss AJ, Zareba W, Hall WJ, et al. Prophylactic implantation of a defibrillator in patients with myocardial infarction and reduced ejection fraction. N Engl J Med. 2002;346(12):877-83. 3. Bardy GH, Lee KL, Mark DB, et al. Amiodarone or an implantable cardioverterdefibrillator for congestive heart failure. N Engl J Med. 2005;352(3):225-37. 4. Bristow MR, Saxon LA, Boehmer J, et al. Cardiac-resynchronization therapy with or without an implantable defibrillator in advanced chronic heart failure. N Engl J Med. 2004;350(21):2140-50. 5. Epstein AE, DiMarco JP, Ellenbogen KA, et al. 2012 ACCF/AHA/HRS focused update incorporated into the ACCF/AHA/HRS 2008 guidelines for device-based therapy of cardiac rhythm abnormalities: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol. 2013;61(3):e6-75. 6. Poole JE, Johnson GW, Hellkamp AS, et al. Prognostic importance of defibrillator shocks in patients with heart failure. N Engl J Med. 2008;359(10):1009-17. 7. Ruwald AC, Schuger C, Moss AJ, et al. Mortality reduction in relation to implantable cardioverter defibrillator programming in the Multicenter Automatic Defibrillator Implantation Trial-Reduce Inappropriate Therapy (MADIT-RIT). Circ Arrhythm Electrophysiol. 2014;7(5):785-92. 8. Daubert JP, Zareba W, Cannom DS, et al. Inappropriate implantable cardioverterdefibrillator shocks in MADIT II: frequency, mechanisms, predictors, and survival impact. J Am Coll Cardiol. 2008;51(14):1357-65. 9. Ellenbogen KA, Levine JH, Berger RD, et al. Are implantable cardioverter defibrillator shocks a surrogate for sudden cardiac death in patients with nonischemic cardiomyopathy? Circulation. 2006;113(6):776-82. 10. Gasparini M, Proclemer A, Klersy C, et al. Effect of long-detection interval vs standarddetection interval for implantable cardioverter-defibrillators on antitachycardia pacing and shock delivery: the ADVANCE III randomized clinical trial. JAMA. 2013;309(18):1903-11.
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11. Moss AJ, Schuger C, Beck CA, et al. Reduction in inappropriate therapy and mortality through ICD programming. N Engl J Med. 2012;367(24):2275-83. 12. Saeed M, Neason CG, Razavi M, et al. Programming antitachycardia pacing for primary prevention in patients with implantable cardioverter defibrillators: results from the PROVE trial. J Cardiovasc Electrophysiol. 2010;21(12):1349-54. 13. Wilkoff BL, Williamson BD, Stern RS, et al. Strategic programming of detection and therapy parameters in implantable cardioverter-defibrillators reduces shocks in primary prevention patients: results from the PREPARE (Primary Prevention Parameters Evaluation) study. J Am Coll Cardiol. 2008;52(7):541-50. 14. Wilkoff BL, Ousdigian KT, Sterns LD, et al. A comparison of empiric to physiciantailored programming of implantable cardioverter-defibrillators: results from the prospective randomized multicenter EMPIRIC trial. J Am Coll Cardiol. 2006;48(2):330-9. 15. Gasparini M, Menozzi C, Proclemer A, et al. A simplified biventricular defibrillator with fixed long detection intervals reduces implantable cardioverter defibrillator (ICD) interventions and heart failure hospitalizations in patients with non-ischaemic cardiomyopathy implanted for primary prevention: the RELEVANT [Role of long dEtection window programming in patients with LEft VentriculAr dysfunction, Non-ischemic eTiology in primary prevention treated with a biventricular ICD] study. Eur Heart J. 2009;30(22):2758-67. 16. Tan VH, Wilton SB, Kuriachan V, Sumner GL, Exner DV. Impact of programming strategies aimed at reducing nonessential implantable cardioverter defibrillator therapies on mortality: a systematic review and meta-analysis. Circ Arrhythm Electrophysiol. 2014;7(1):16470. 17. Wilkoff BL, Fauchier L, Stiles MK, et al. 2015 HRS/EHRA/APHRS/SOLAECE expert consensus statement on optimal implantable cardioverter-defibrillator programming and testing. Heart Rhythm. 2016;13(2):e50-86. 18. Stiles MK, Fauchier L, Morillo CA, Wilkoff BL, 2019 HRS/EHRA/APHRS/LAHRS focused update to 2015 HRS/EHRA/APHRS/SOLAECE expert consensus statement on optimal implantable cardioverter-defibrillator programming and testing. EP Europace, 2019;21(9): 1442– 43. 19. Auricchio A, Schloss EJ, Kurita T, et al. Low inappropriate shock rates in patients with single- and dual/triple-chamber implantable cardioverter-defibrillators using a novel suite of detection algorithms: PainFree SST trial primary results. Heart Rhythm. 2015;12(5):926-36. 20. Wathen MS, Sweeney MO, DeGroot PJ, et al. Shock reduction using antitachycardia pacing for spontaneous rapid ventricular tachycardia in patients with coronary artery disease. Circulation. 2001;104(7):796-801. 21. Wathen MS, DeGroot PJ, Sweeney MO, et al. Prospective randomized multicenter trial of empirical antitachycardia pacing versus shocks for spontaneous rapid ventricular tachycardia
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in patients with implantable cardioverter-defibrillators: Pacing Fast Ventricular Tachycardia Reduces Shock Therapies (PainFREE Rx II) trial results. Circulation. 2004;110(17):2591-6. 22. Kutyifa V, Daubert JP, Olshansky B, et al. Characterization and predictors of first and subsequent inappropriate ICD therapy by heart rate ranges: Result of the MADIT-RIT efficacy analysis. Heart Rhythm. 2015;12(9):2030-7. 23. Ruwald MH, Okumura K, Kimura T, Aonuma K, et al. Syncope in high-risk cardiomyopathy patients with implantable defibrillators: frequency, risk factors, mechanisms, and association with mortality: results from the multicenter automatic defibrillator implantation trial-reduce inappropriate therapy (MADIT-RIT) study. Circulation. 2014;129(5):545-52. 24. Thogersen AM, Larsen JM, Johansen JB, Abedin M, Swerdlow CD. Failure to Treat Life-Threatening Ventricular Tachyarrhythmias in Contemporary Implantable CardioverterDefibrillators: Implications for Strategic Programming. Circ Arrhythm Electrophysiol. 2017;10(9).
Figure Legends Figure 1: Kaplan-Meier survival curve showed cumulative Incidence of endpoints.
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Table 1 Baseline Patient Characteristics NGC Group (n = 514)
GC Group (n = 258)
p Value
Age (yrs)
64.8 ± 13.7
60.3 ± 13.5
<0.01
Female sex
174 (33.9%)
92 (35.7%)
0.62
Race
0.16
White
358 (69.6%)
163 (63.2%)
Black
148 (28.8%)
86 (33.3%)
Asian
6 (1.2%)
7 (2.7%)
American Indian
2 (0.4%)
2 (0.8%)
NYHA
0.28
Class I
36 (7.0%)
27 (10.5%)
Class II
218 (42.4%)
115 (44.6%)
Class III
250 (48.6%)
111 (43.0%)
Class IV
10 (1.9%)
5 (1.9%)
27.0 ± 11.6
26.2 ± 11.5
0.36
Non-Ischemic cardiomyopathy
259 (50.4%)
131 (50.8%)
0.92
Ischemic cardiomyopathy
231 (44.9%)
116 (45.0%)
0.99
Coronary artery bypass grafting
105 (20.4%)
46 (17.8%)
0.39
Percutaneous coronary intervention
137 (26.7%)
62 (24.0%)
0.43
42 (8.2%)
13 (5.0%)
0.11
Diabetes mellitus
195 (37.9%)
91 (35.3%)
0.47
Chronic obstructive pulmonary disease
76 (14.8%)
28 (10.9%)
0.13
Obstructive sleep apnea
99 (19.3%)
49 (19.0%)
0.93
Renal disease
65 (12.9%)
34 (13.2%)
0.84
Cerebrovascular disease
53 (10.3%)
37 (14.3%)
0.10
Atrial fibrillation
180 (35.0%)
78 (30.2%)
0.18
24 (4.7%)
15 (5.8%)
0.49
Left ventricular ejection fraction (%) Comorbidities at baseline
Valvular heart disease
PSVT Medications
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ACE inhibitor
298 (58.0%)
145 (56.2%)
0.64
Angiotensin II receptor blocker
95 (18.5%)
65 (25.2%)
0.03
Beta-Blocker
457 (88.9%)
234 (90.7%)
0.45
Antiarrhythmic drugs
64 (11.9%)
30 (11.6%)
0.92
Statin
344 (66.9%)
154 (59.7%)
0.05
Antiplatelet
277 (53.9%)
171 (66.3%)
<0.01
Oral anticoagulation
148 (28.8%)
68 (26.4%)
0.48
2.1 + 0.9
1.9 + 0.9
<0.01
Follow up time (yrs)
Values are mean + SD or n (%). ACE = angiotensin-converting enzyme; GC = guideline concordant; NGC = non-guideline concordant; NYHA = New York Heart Association; PSVT = paroxysmal supraventricular tachycardia
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Table 2 Device Characteristics NGC Group (n = 514)
GC Group (n = 258)
Type
0.02
Single chamber ICD
163 (31.7%)
106 (41.1%)
Dual chamber ICD
147 (28.6%)
57 (22.1%)
CRT-D
204 (39.7%)
95 (36.8%)
Manufacturer Biotronik
p Value
<0.01 39 (7.6%)
6 (2.3%)
Boston Scientific
237(46.1%)
112 (43.4%)
Medtronic
82 (16.0%)
140 (54.3%)
SJM
156 (30.4%)
0 (0.0%)
Values are mean + SD or n (%). CRT-D = cardiac-resynchronization therapy with defibrillator; GC = guideline concordant; ICD = implantable cardioverter–defibrillator; NGC = non-guideline concordant; SJM = St. Jude Medical
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Table 3 Details of delivered therapy and mortality NGC group (n = 514)
GC group (n = 258)
p Value
ICD Therapy
110 (21.4%)
27 (10.5%)
<0.01
ICD Shock
61 (11.9%)
17 (6.6%)
0.02
Death
41 (8.0%)
13 (5.0%)
0.13
Values are n (%) of patients; the percentage is calculated from the total number of patients with the first occurrence of events during follow up and the total number of persons in each group. The mean follow up time in NGC group was 2.1 + 0.9 years vs. 1.9 + 0.9 years in GC group. GC = guideline concordant; ICD = implantable cardioverter–defibrillator; NGC = non-guideline concordant
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Table 4 Multivariate for ICD Therapy and Shock Therapy (Cox regression analysis model) Hazard Ratio [95% CI]
p Value
GC group
0.47 [0.29 - 0.75]
<0.01
Female sex
0.62 [0.42 - 0.91]
0.02
ICD Therapy
NYHA Class I
1.00
Class II
0.65 [0.37 – 1.14]
0.13
Class III
0.61 [0.35 – 1.07]
0.09
Class IV
0.94 [0.27 – 3.24]
0.92
Diabetes mellitus
0.71 [0.49 – 1.04]
0.08
PSVT
2.05 [1.09 – 3.86]
0.03
Angiotensin II receptor blocker
0.69 [0.43 – 1.10]
0.12
Manufacturer Boston Scientific
1.00
Biotronik
0.62 [0.29 – 1.37]
0.24
Medtronic
0.90 [0.56 – 1.43]
0.65
SJM
0.83 [0.53 – 1.29]
0.40
GC group
0.50 [0.27 - 0.91]
0.02
Age
0.99 [0.97 - 1.00]
0.11
Female sex
0.39 [0.22 - 0.68]
<0.01
Ischemic cardiomyopathy
1.02 [0.76 – 1.35]
0.92
Percutaneous coronary intervention
0.52 [0.26 – 1.06]
0.07
Shock Therapy
Manufacturer Boston Scientific
1.00
Biotronik
0.62 [0.22 – 1.75]
0.37
Medtronic
0.89 [0.48 – 1.64]
0.70
SJM
0.65 [0.33 – 1.29]
0.22
GC = guideline concordant; ICD = implantable cardioverter–defibrillator; NGC = non-guideline concordant; NYHA = New York Heart Association; PSVT = paroxysmal supraventricular tachycardia; SJM = St. Jude Medical
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A
B
C
Figure 1
1
S1547-5271(20)30093-X
DOI:
https://doi.org/10.1016/j.hrthm.2020.02.004
Reference:
HRTHM 8274
To appear in:
Heart Rhythm
Received Date: 16 December 2019 Accepted Date: 1 February 2020
Please cite this article as: Ananwattanasuk T, Tanawuttiwat T, Chokesuwattanaskul R, Lathkar-Pradhan S, Barham W, Oral H, Thakur RK, Jongnarangsin K, Programming Implantable Cardioverter Defibrillator in Primary Prevention: Guideline Concordance and Outcomes, Heart Rhythm (2020), doi: https:// doi.org/10.1016/j.hrthm.2020.02.004. This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. © 2020 Published by Elsevier Inc. on behalf of Heart Rhythm Society.
Programming Implantable Cardioverter Defibrillator in Primary Prevention: Guideline Concordance and Outcomes
Running Title: Ananwattanasuk et al.; Guideline concordance and outcomes in ICD programming
Teetouch Ananwattanasuk, MDa,b; Tanyanan Tanawuttiwat, MD, MPHc; Ronpichai Chokesuwattanaskul, MDa; Sangeeta Lathkar-Pradhan, MBBSa; Waseem Barham, MDd, Hakan Oral, MD, FHRSa; Ranjan K. Thakur, MD, MPH, MBAd; Krit Jongnarangsin, MDa
a
Cardiac Electrophysiology, University of Michigan Health System, Ann Arbor, Michigan; Cardiology Division, Department of Internal Medicine, Vajira Hospital, Navamindradhiraj University, Thailand; cDivision of Cardiology, Department of Medicine, University of Mississippi Medical Center, Jackson, Mississippi; dCardiac Electrophysiology, Michigan State University and Sparrow Thoracic and Cardiovascular Institute, Lansing, Michigan b
Funding: None Address for Correspondence: Krit Jongnarangsin, MD Cardiac Electrophysiology, University of Michigan Health System, 1500 E Medical Center Dr SPC 5856, Ann Arbor, MI 48109-5856 Email: [email protected] Disclosures: None. Acknowledgments: None. *A portion of the results were presented at the 2018 AHA Scientific Sessions
Word Count: 4190
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Abstract Background: Inappropriate therapy is a common adverse effect in patients with implantable cardioverter defibrillator (ICD) that may be prevented by appropriate programming. Objectives: The study aims to assess outcomes of the device programming based on a 2015 HRS/EHRA/APHRS/SOLAECE expert consensus statement and a 2019 focused update on optimal implantable cardioverter-defibrillator programming and testing. Methods: Consecutive patients who underwent ICD for primary prevention during 2014-2016 at 3 centers were included in the retrospective analysis. The patients were classified into 2 groups based on the tachycardia programming at the time of implant: guideline concordant group (GC) and non-guideline concordant group (NGC). Kaplan-Meier analysis and Cox proportional hazard models were used to estimate freedom from ICD therapy (ATP or shock), ICD shock and death. Results: A total of 772 patients were included in the study (mean age 63.3 ± 13.8 years). Of this total, 258 patients (33.4%) were in GC group and 514 patients (66.6%) were in NGC group. During the mean follow up of 2.02 ± 0.91 years, guideline concordant programming was associated with a 53% reduction in ICD therapy (p < 0.01) and 50% reduction in ICD shock (p 0.02). There were no significant differences in mortality (6% in GC group vs.11% in NGC group, p 0.22). Conclusion: Only 1/3 of the studied population had ICD device programmed in concordance with the current guidelines. ICD programming based on the current guidelines was associated with a significantly lower rate of ICD therapy and shock without changes in mortality during intermediate-term follow up.
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Keywords: Implantable Cardioverter Defibrillator, ICD programming guideline, ICD shock, ICD therapy, Primary prevention
Introduction The implantable cardioverter defibrillator (ICD), either alone or in conjunction with cardiac resynchronization therapy (CRT) is highly effective in reducing mortality among patients at risk for fatal arrhythmias. As such, ICD implantation has long become the standard of cardiovascular care in appropriate patients based on detailed guidelines and backed by a board literature base (1-5). However, there are accumulated evidence that non-essential ICD therapies, particularly for non-sustained ventricular tachycardia (VT), and inappropriate shocks for supraventricular tachyarrhythmias (SVTs), atrial fibrillation, and noise affect up to 8-40% of patients and may actually increase morbidity and mortality (6-9). Several randomized trials and prospective studies have examined the effect of ICD programming designed to reduce inappropriate shocks by increasing both detection duration and detection heart rates (7, 10-15). Furthermore, manufacturer technological improvements have aimed at reducing unnecessary ICD therapy by improving discriminators of SVTs and algorithms designed to reduce oversensing. In a meta-analysis encompassing a total of 7687 patients, ICD therapy reduction strategy resulted in a 30% decrease in all-cause mortality when compared to conventional programming (16). This mortality decrease can largely be attributed to a 50% reduction in inappropriate shocks. However, 1 death may have been related to ICD therapy reduction programming (13). This may hint towards the possible trade-off between ICD therapy 3
reduction programming strategies and failure to treat episodes of VT or ventricular fibrillation (VF) and may reflect less controlled settings outside of study protocols. HRS/EHRA/APHRS/SOLAECE issued an expert consensus statement on optimal implantable cardioverter-defibrillator programming and testing in 2015(17) as well as a focused update in 2019(18), based on the current evidence from clinical trials. The current study aims to 1) evaluate the real-world ICD programming among patients with an ICD implant for primary prevention and its concordance with the 2015 HRS/EHRA/APHRS/SOLAECE expert consensus statement as well as the 2019 focused update on optimal implantable cardioverter-defibrillator programming and testing and 2) compare the occurrence of the ICD therapies and mortality in patients who have ICD parameters programmed following the guidelines and those who have the ICD programmed outside the guidelines. Methods Study Population Consecutive adult patients who underwent initial transvenous ICDs or CRT-Ds implant for primary prevention indication (5) at 3 tertiary care hospitals, including University of Michigan, Michigan State University, and University of Mississippi Medical Center, from January 2014 to December 2016 were included. Patients who had a follow up duration of less than 3 months or missing initial ICD programming parameter data were excluded from the study. Databases from 3 centers were reviewed and collated in a blinded fashion for review by the investigators. The present study was approved by the institutional review boards for each of the participating centers. Data collection and Definitions
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Data collection was performed by reviewing medical records for baseline characteristics, implantation data and follow-up data on clinical outcomes, therapy delivery, and death. The patient was categorized according to whether the device programming followed the 2015 HRS/EHRA/APHRS/SOLAECE expert consensus statement (Appendix B Manufacturer Specific Translation of ICD Programming Recommendations) and the 2019 focused update on optimal implantable cardioverter-defibrillator programming and testing. The guideline concordant group (GC) was defined as patients who had ICD programming following the guideline recommendations at the time of implant, with all of the following criteria: 1)
Tachyarrhythmia detection duration criteria was programmed to allow the tachycardia to continue for at least 6 seconds or for 30 intervals before completing detection. A detection duration of 2.5 seconds is allowed for detection rate ≥250 bpm (high-rate therapy option) and a detection interval of 24 is allowed if a 30interval delay is not programmable.
2)
The slowest tachycardia therapy zone limit show was programmed between 185 and 200 bpm.
3)
The discrimination algorithms to distinguish SVT from VT was programmed on unless complete heart block was present.
4)
ATP therapy was programmed on for all ventricular tachyarrhythmia detection zones with available ATP therapy.
The non-guideline concordant group (NGC) was defined as patients who had ICD programming that differed from the guideline recommendations
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Statistical Analysis Categorical variables were presented as numbers and percentages and were compared for the entire cohort using Chi-square test and Fisher’s exact test as appropriate. The continuous variables are presented as mean ± SD and compared using the Student t-test or Mann-Whitney U-test. In the primary analysis, a Cox proportional hazards regression model was used to estimate the risk of a first occurrence of any therapy, shock, and all-cause mortality. Cox model variables with a p-value < 0.10 were considered to have actually interfered with the survival of the patients. A p-value of 0.05 was deemed to be statistically significant. We constructed Kaplan-Meier graphs for the primary and secondary endpoints with a log-rank test for significant testing. Crude rates of first therapy, first shock, and death were compared with the use of Chisquare tests. All statistics will be analyzed by Stata, version 15.0 (Stata Corp LP, College Station, TX) and SPSS 23.0 software (SPSS Inc., Chicago, IL, USA). Results Study Population A total of 831 patients were reviewed and 59 patients were excluded from the study due to the lack of initial programming data or insufficient follow-up time. The baseline clinical characteristics of patients are presented in Table 1. The mean age was 63.3 ± 13.8 years and 66.1 % of patients were male. Of the 772 included patients, 258 patients (33.4%) were in GC group and 514 patients (66.6%) in NGC group. The mean follow up duration was 2.0 ± 0.9 years. Baseline characteristics ofNCG group were comparable to GC group except for significantly older age (64.8 ± 13.7 vs 60.3 ± 13.5, p value < 0.01), longer follow up duration (2.1+0.92 years
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vs 1.9+0.9 years, p value < 0.01), lower rate of antiplatelet used (53.9% vs 66.3%, p value < 0.01), and lower rate of ARBs used (18.5% vs 25.2%, p value 0.03). The type and distribution of device manufacturers was significantly different in both groups (p value 0.02 and p value < 0.01, respectively). Devices were programmed in concordance with the guideline in 6 of 45 (13.3%) Biotronik devices, 112 of 349 (32.1%) Boston Scientific devices, 140 of 222 (63.6%) Medtronic devices, and 0 of 156 St. Jude Medical devices (Table 2). ICD Therapies and Mortality Among the 772 patients, 137 patients (17.7%) received ICD therapy (ATP or shock), 78 patients (10.1%) received ICD shock, and 54 patients (7.0%) died (Table 3). Univariate analysis showed that the risk of ICD therapy was significantly lower in GC group (HR: 0.49, 95% CI: 0.32 – 0.75, p<0.01), female (HR: 0.62, 95% CI: 0.42 – 0.91, p 0.01) and those with diabetes (HR: 0.69, 95% CI: 0.47 – 0.99, p 0.04). The risk of ICD shock was also significantly lower in GC group (HR: 0.58, 95% CI: 0.34 – 0.99, p 0.04), female (HR: 0.43, 95% CI: 0.25 – 0.76, p<0.01) and those who had PCI (HR: 0.52, 95% CI: 0.28 – 0.97, p 0.04). Among device manufacturers comparing to Boston Scientific, Medtronic devices had a lower rate of ICD therapy (HR: 0.62, 95% CI: 0.40 – 0.95, p 0.03). Multivariate Cox regression analysis (Table 4) showed that Guideline concordant ICD programming was associated with a 53% reduction in any ICD therapy (HR: 0.47, 95% CI: 0.29 - 0.75, p<0.01) and a 50% reduction in ICD shock (HR: 0.50, 95% CI: 0.27-0.91, p 0.02). The risk of ICD therapy and ICD shock were reduced by 38% (HR: 0.62, 95% CI: 0.42 – 0.91, p 0.02) and 61% (HR: 0.39, 95% CI: 0.22 – 0.68, p<0.01), respectively in females. History of paroxysmal supraventricular tachycardia was associated with a higher risk of ICD therapy (HR: 2.05, 95% CI: 1.09 – 3.86, p 0.03). However, device 7
manufacturer was not found to be an independent predictor for either ICD therapy or ICD shock. Kaplan-Meier survival curve (Figure 1) showed a significantly lower estimated 3-year incidence of ICD therapy (13% vs. 29%, p < 0.01) and ICD shock (7% vs. 17%, p 0.04) in GC group. There was no significant difference in mortality at 3 years between GC and NGC groups (6% vs. 11%, p 0.22). Discussion The present study shows that tachycardia detection in the majority of patients who underwent ICD/CRT-D implant for primary prevention was not programmed as recommended by the current guidelines (18). Default ICD setting in each manufacturer might be an important factor that affects the compliance with the guideline. Among all manufacturers, patients with Medtronic devices had the highest proportion of guideline concordant ICD programming. Default tachycardia detection of Medtronic devices is similar to the programming in the previous trials (10, 19) and the current guidelines which requires no programming changes at the implant. ICD settings recommended in the guidelines were developed based upon prior studies including algorithms for discrimination of supraventricular tachycardia, prolonged duration of arrhythmia detection, faster rates for tachycardia detection, and anti-tachycardia pacing (13, 14, 2021)
. The overriding principle is to be certain that there is a sustained tachyarrhythmia before
treating the rhythm and that the treated rhythm is ventricular arrhythmias, not supraventricular arrhythmias. Our study demonstrated that programming ICD therapies following the guideline statement was associated with reductions in ICD therapy and shock without changes in mortality during intermediate-term follow up. The reduction of ICD therapy was due to both decreases in inappropriate therapies and avoidable therapies. The reduction in inappropriate therapies is most likely from SVT discrimination function recommended by the current guidelines. MADIT-RIT 8
showed that the majority of the inappropriate therapies from atrial arrhythmia occurred in the range of 170-199 bpm and that the ample majority of those arrhythmias were caused by regular supraventricular arrhythmia, resulting in failure of traditional device algorithms such as sudden onset, stability, and atrioventricular relationship to discriminate between atrial and ventricular tachyarrhythmias in this range (22). Inappropriate therapies delivered for rhythm above 200 bpm were less prevalent and were more frequently caused by atrial fibrillation, atrial flutter or oversensing. At this rapid rate, the prolonged duration of arrhythmia detection was the only effective strategy that significantly reduced inappropriate therapies (22). There are some concerns about safety and the potential risks from delay therapy, syncope or failure to detect when the device is programmed with high detection rates and prolonged arrhythmia detection. MADIT-RIT trial showed that ICD programming with therapy for ventricular tachycardia ≥200 bpm or a long delay is not associated with increased risk of arrhythmogenic or all-cause syncope, and syncope caused by slow ventricular tachycardias (<200 bpm) is a rare event (23). Nonetheless, the recent case series by Thogersen AM et al. raised this concern. The investigators reported that no patient with manufacturer-specific programming validated in clinical trials failed to receive an initial, timely shock for ventricular fibrillation. However, most of the studied patients who did not receive timely ventricular fibrillation shocks had ICDs programmed according to guidelines extrapolated from evidence obtained by using another manufacturer’s ICDs with different sensing and detection features. The study concluded that complex and unanticipated interactions between manufacturer-specific features and generic programming can prevent therapy for VF. More data are needed to assess the risks and benefits of translating evidence-based detection parameters from one manufacturer to another (24). Study limitations 9
The study is a non-randomized retrospective study with a limited number of participants. The decision of the device programming was not randomized and was based on physician’s discretion. Therefore, there is a high heterogeneity of patient selections and device programming in the NGC group. these factors potentially have effects on the outcomes of the study. Due to the possibility of device programming changes after the first therapy and possible impact to the outcome from the changes, the following therapies were not evaluated. The limitation in evaluating only the first occurrence of therapy may not reflect the long-term outcomes of guideline-based programming. As previously mention, there are some possible effects from the manufacturer specific algorithm for managing ventricular arrhythmias and SVT discrimination. The data on the follow-up echocardiogram is not available. The patients with CRT-D device were included in the study and were accounted for 38.7% of studied populations. The improved LVEF may affect the occurrence of ICD therapy. The number of events and deaths in the withinguideline group in this study is small and may have limited power. The adjudications of the therapies whether they were appropriate were not done due to the potential inaccuracy in patients with single-chamber ICD. However, the GC group was associated with a significantly lower rate of ICD therapy and shock without changes in mortality. For the generalizability, this study is limited to patients with primary prevention ICD indication and the results cannot be applied to those with secondary prevention ICD indications. Conclusion Only one third of the studied population had devices programmed as recommended by 2015 HRS/EHRA/APHRS/SOLAECE expert consensus statement and 2019 focused update on optimal implantable cardioverter-defibrillator programming and testing. Programming ICD
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therapies following the guideline statement was associated with reductions in ICD therapy and shock without changes in mortality during intermediate-term follow up. Reference 1. Moss AJ, Hall WJ, Cannom DS, et al. Improved survival with an implanted defibrillator in patients with coronary disease at high risk for ventricular arrhythmia. Multicenter Automatic Defibrillator Implantation Trial Investigators. N Engl J Med. 1996;335(26):1933-40. 2. Moss AJ, Zareba W, Hall WJ, et al. Prophylactic implantation of a defibrillator in patients with myocardial infarction and reduced ejection fraction. N Engl J Med. 2002;346(12):877-83. 3. Bardy GH, Lee KL, Mark DB, et al. Amiodarone or an implantable cardioverterdefibrillator for congestive heart failure. N Engl J Med. 2005;352(3):225-37. 4. Bristow MR, Saxon LA, Boehmer J, et al. Cardiac-resynchronization therapy with or without an implantable defibrillator in advanced chronic heart failure. N Engl J Med. 2004;350(21):2140-50. 5. Epstein AE, DiMarco JP, Ellenbogen KA, et al. 2012 ACCF/AHA/HRS focused update incorporated into the ACCF/AHA/HRS 2008 guidelines for device-based therapy of cardiac rhythm abnormalities: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol. 2013;61(3):e6-75. 6. Poole JE, Johnson GW, Hellkamp AS, et al. Prognostic importance of defibrillator shocks in patients with heart failure. N Engl J Med. 2008;359(10):1009-17. 7. Ruwald AC, Schuger C, Moss AJ, et al. Mortality reduction in relation to implantable cardioverter defibrillator programming in the Multicenter Automatic Defibrillator Implantation Trial-Reduce Inappropriate Therapy (MADIT-RIT). Circ Arrhythm Electrophysiol. 2014;7(5):785-92. 8. Daubert JP, Zareba W, Cannom DS, et al. Inappropriate implantable cardioverterdefibrillator shocks in MADIT II: frequency, mechanisms, predictors, and survival impact. J Am Coll Cardiol. 2008;51(14):1357-65. 9. Ellenbogen KA, Levine JH, Berger RD, et al. Are implantable cardioverter defibrillator shocks a surrogate for sudden cardiac death in patients with nonischemic cardiomyopathy? Circulation. 2006;113(6):776-82. 10. Gasparini M, Proclemer A, Klersy C, et al. Effect of long-detection interval vs standarddetection interval for implantable cardioverter-defibrillators on antitachycardia pacing and shock delivery: the ADVANCE III randomized clinical trial. JAMA. 2013;309(18):1903-11.
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11. Moss AJ, Schuger C, Beck CA, et al. Reduction in inappropriate therapy and mortality through ICD programming. N Engl J Med. 2012;367(24):2275-83. 12. Saeed M, Neason CG, Razavi M, et al. Programming antitachycardia pacing for primary prevention in patients with implantable cardioverter defibrillators: results from the PROVE trial. J Cardiovasc Electrophysiol. 2010;21(12):1349-54. 13. Wilkoff BL, Williamson BD, Stern RS, et al. Strategic programming of detection and therapy parameters in implantable cardioverter-defibrillators reduces shocks in primary prevention patients: results from the PREPARE (Primary Prevention Parameters Evaluation) study. J Am Coll Cardiol. 2008;52(7):541-50. 14. Wilkoff BL, Ousdigian KT, Sterns LD, et al. A comparison of empiric to physiciantailored programming of implantable cardioverter-defibrillators: results from the prospective randomized multicenter EMPIRIC trial. J Am Coll Cardiol. 2006;48(2):330-9. 15. Gasparini M, Menozzi C, Proclemer A, et al. A simplified biventricular defibrillator with fixed long detection intervals reduces implantable cardioverter defibrillator (ICD) interventions and heart failure hospitalizations in patients with non-ischaemic cardiomyopathy implanted for primary prevention: the RELEVANT [Role of long dEtection window programming in patients with LEft VentriculAr dysfunction, Non-ischemic eTiology in primary prevention treated with a biventricular ICD] study. Eur Heart J. 2009;30(22):2758-67. 16. Tan VH, Wilton SB, Kuriachan V, Sumner GL, Exner DV. Impact of programming strategies aimed at reducing nonessential implantable cardioverter defibrillator therapies on mortality: a systematic review and meta-analysis. Circ Arrhythm Electrophysiol. 2014;7(1):16470. 17. Wilkoff BL, Fauchier L, Stiles MK, et al. 2015 HRS/EHRA/APHRS/SOLAECE expert consensus statement on optimal implantable cardioverter-defibrillator programming and testing. Heart Rhythm. 2016;13(2):e50-86. 18. Stiles MK, Fauchier L, Morillo CA, Wilkoff BL, 2019 HRS/EHRA/APHRS/LAHRS focused update to 2015 HRS/EHRA/APHRS/SOLAECE expert consensus statement on optimal implantable cardioverter-defibrillator programming and testing. EP Europace, 2019;21(9): 1442– 43. 19. Auricchio A, Schloss EJ, Kurita T, et al. Low inappropriate shock rates in patients with single- and dual/triple-chamber implantable cardioverter-defibrillators using a novel suite of detection algorithms: PainFree SST trial primary results. Heart Rhythm. 2015;12(5):926-36. 20. Wathen MS, Sweeney MO, DeGroot PJ, et al. Shock reduction using antitachycardia pacing for spontaneous rapid ventricular tachycardia in patients with coronary artery disease. Circulation. 2001;104(7):796-801. 21. Wathen MS, DeGroot PJ, Sweeney MO, et al. Prospective randomized multicenter trial of empirical antitachycardia pacing versus shocks for spontaneous rapid ventricular tachycardia
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in patients with implantable cardioverter-defibrillators: Pacing Fast Ventricular Tachycardia Reduces Shock Therapies (PainFREE Rx II) trial results. Circulation. 2004;110(17):2591-6. 22. Kutyifa V, Daubert JP, Olshansky B, et al. Characterization and predictors of first and subsequent inappropriate ICD therapy by heart rate ranges: Result of the MADIT-RIT efficacy analysis. Heart Rhythm. 2015;12(9):2030-7. 23. Ruwald MH, Okumura K, Kimura T, Aonuma K, et al. Syncope in high-risk cardiomyopathy patients with implantable defibrillators: frequency, risk factors, mechanisms, and association with mortality: results from the multicenter automatic defibrillator implantation trial-reduce inappropriate therapy (MADIT-RIT) study. Circulation. 2014;129(5):545-52. 24. Thogersen AM, Larsen JM, Johansen JB, Abedin M, Swerdlow CD. Failure to Treat Life-Threatening Ventricular Tachyarrhythmias in Contemporary Implantable CardioverterDefibrillators: Implications for Strategic Programming. Circ Arrhythm Electrophysiol. 2017;10(9).
Figure Legends Figure 1: Kaplan-Meier survival curve showed cumulative Incidence of endpoints.
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Table 1 Baseline Patient Characteristics NGC Group (n = 514)
GC Group (n = 258)
p Value
Age (yrs)
64.8 ± 13.7
60.3 ± 13.5
<0.01
Female sex
174 (33.9%)
92 (35.7%)
0.62
Race
0.16
White
358 (69.6%)
163 (63.2%)
Black
148 (28.8%)
86 (33.3%)
Asian
6 (1.2%)
7 (2.7%)
American Indian
2 (0.4%)
2 (0.8%)
NYHA
0.28
Class I
36 (7.0%)
27 (10.5%)
Class II
218 (42.4%)
115 (44.6%)
Class III
250 (48.6%)
111 (43.0%)
Class IV
10 (1.9%)
5 (1.9%)
27.0 ± 11.6
26.2 ± 11.5
0.36
Non-Ischemic cardiomyopathy
259 (50.4%)
131 (50.8%)
0.92
Ischemic cardiomyopathy
231 (44.9%)
116 (45.0%)
0.99
Coronary artery bypass grafting
105 (20.4%)
46 (17.8%)
0.39
Percutaneous coronary intervention
137 (26.7%)
62 (24.0%)
0.43
42 (8.2%)
13 (5.0%)
0.11
Diabetes mellitus
195 (37.9%)
91 (35.3%)
0.47
Chronic obstructive pulmonary disease
76 (14.8%)
28 (10.9%)
0.13
Obstructive sleep apnea
99 (19.3%)
49 (19.0%)
0.93
Renal disease
65 (12.9%)
34 (13.2%)
0.84
Cerebrovascular disease
53 (10.3%)
37 (14.3%)
0.10
Atrial fibrillation
180 (35.0%)
78 (30.2%)
0.18
24 (4.7%)
15 (5.8%)
0.49
Left ventricular ejection fraction (%) Comorbidities at baseline
Valvular heart disease
PSVT Medications
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ACE inhibitor
298 (58.0%)
145 (56.2%)
0.64
Angiotensin II receptor blocker
95 (18.5%)
65 (25.2%)
0.03
Beta-Blocker
457 (88.9%)
234 (90.7%)
0.45
Antiarrhythmic drugs
64 (11.9%)
30 (11.6%)
0.92
Statin
344 (66.9%)
154 (59.7%)
0.05
Antiplatelet
277 (53.9%)
171 (66.3%)
<0.01
Oral anticoagulation
148 (28.8%)
68 (26.4%)
0.48
2.1 + 0.9
1.9 + 0.9
<0.01
Follow up time (yrs)
Values are mean + SD or n (%). ACE = angiotensin-converting enzyme; GC = guideline concordant; NGC = non-guideline concordant; NYHA = New York Heart Association; PSVT = paroxysmal supraventricular tachycardia
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Table 2 Device Characteristics NGC Group (n = 514)
GC Group (n = 258)
Type
0.02
Single chamber ICD
163 (31.7%)
106 (41.1%)
Dual chamber ICD
147 (28.6%)
57 (22.1%)
CRT-D
204 (39.7%)
95 (36.8%)
Manufacturer Biotronik
p Value
<0.01 39 (7.6%)
6 (2.3%)
Boston Scientific
237(46.1%)
112 (43.4%)
Medtronic
82 (16.0%)
140 (54.3%)
SJM
156 (30.4%)
0 (0.0%)
Values are mean + SD or n (%). CRT-D = cardiac-resynchronization therapy with defibrillator; GC = guideline concordant; ICD = implantable cardioverter–defibrillator; NGC = non-guideline concordant; SJM = St. Jude Medical
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Table 3 Details of delivered therapy and mortality NGC group (n = 514)
GC group (n = 258)
p Value
ICD Therapy
110 (21.4%)
27 (10.5%)
<0.01
ICD Shock
61 (11.9%)
17 (6.6%)
0.02
Death
41 (8.0%)
13 (5.0%)
0.13
Values are n (%) of patients; the percentage is calculated from the total number of patients with the first occurrence of events during follow up and the total number of persons in each group. The mean follow up time in NGC group was 2.1 + 0.9 years vs. 1.9 + 0.9 years in GC group. GC = guideline concordant; ICD = implantable cardioverter–defibrillator; NGC = non-guideline concordant
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Table 4 Multivariate for ICD Therapy and Shock Therapy (Cox regression analysis model) Hazard Ratio [95% CI]
p Value
GC group
0.47 [0.29 - 0.75]
<0.01
Female sex
0.62 [0.42 - 0.91]
0.02
ICD Therapy
NYHA Class I
1.00
Class II
0.65 [0.37 – 1.14]
0.13
Class III
0.61 [0.35 – 1.07]
0.09
Class IV
0.94 [0.27 – 3.24]
0.92
Diabetes mellitus
0.71 [0.49 – 1.04]
0.08
PSVT
2.05 [1.09 – 3.86]
0.03
Angiotensin II receptor blocker
0.69 [0.43 – 1.10]
0.12
Manufacturer Boston Scientific
1.00
Biotronik
0.62 [0.29 – 1.37]
0.24
Medtronic
0.90 [0.56 – 1.43]
0.65
SJM
0.83 [0.53 – 1.29]
0.40
GC group
0.50 [0.27 - 0.91]
0.02
Age
0.99 [0.97 - 1.00]
0.11
Female sex
0.39 [0.22 - 0.68]
<0.01
Ischemic cardiomyopathy
1.02 [0.76 – 1.35]
0.92
Percutaneous coronary intervention
0.52 [0.26 – 1.06]
0.07
Shock Therapy
Manufacturer Boston Scientific
1.00
Biotronik
0.62 [0.22 – 1.75]
0.37
Medtronic
0.89 [0.48 – 1.64]
0.70
SJM
0.65 [0.33 – 1.29]
0.22
GC = guideline concordant; ICD = implantable cardioverter–defibrillator; NGC = non-guideline concordant; NYHA = New York Heart Association; PSVT = paroxysmal supraventricular tachycardia; SJM = St. Jude Medical
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A
B
C
Figure 1
1