EHRA Key References on Pacing for bradycardia

2013 ESC guidelines on cardiac pacing and cardiac resynchronization therapy: the task
force on cardiac pacing and resynchronization therapy of the European Society of
Cardiology (ESC). Developed in collaboration with the European Heart Rhythm
Association (EHRA). European Society of Cardiology (ESC); European Heart Rhythm Association (EHRA),
Brignole M, Auricchio A, Baron-Esquivias G, Bordachar P, Boriani G,
Breithardt OA, Cleland J, Deharo JC, Delgado V, Elliott PM, Gorenek B, Israel CW,
Leclercq C, Linde C, Mont L, Padeletti L, Sutton R, Vardas PE
Europace. 2013 Aug;15(8):1070-118.

The latest guideline on cardiac pacing and resynchronization therapy.

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.
Tracy CM, Epstein AE, Darbar D, Dimarco JP, Dunbar SB, Estes NA 3rd, Ferguson TB Jr, Hammill SC, Karasik PE, Link MS, Marine JE, Schoenfeld MH, Shanker AJ, Silka MJ, Stevenson LW, Stevenson WG, Varosy PD.
J Am Coll Cardiol. 2012 Dec 12

This update of the ACCF/AHA/HRS guidelines from 2008 introduces a new section on remote follow-up and monitoring of CIEDs. The guidelines contain a revised section on cardiac resynchronisation therapy, which is slightly different from the 2010 Focused Update of the ESC Guidelines on device therapy in heart failure.

The CONNECT (Clinical Evaluation of Remote Notification to Reduce Time to Clinical
Decision) trial: the value of wireless remote monitoring with automatic clinician alerts.
Crossley GH, Boyle A, Vitense H, Chang Y, Mead RH; CONNECT Investigators.
J Am Coll Cardiol. 2011 Mar 8;57(10):1181-9.

Wireless remote monitoring with automatic clinician alerts as compared with standard in-office follow-up significantly reduced the time to a clinical decision in response to clinical events and was associated with a significant reduction in mean length of CV hospital stay.

Follow-up of patients with new cardiovascular implantable electronic devices: is adherence tothe experts' recommendations associated with improved outcomes?
Hess PL, Mi X, Curtis LH, Wilkoff BL, Hegland DD, Al-Khatib SM. Heart Rhythm.2013 Aug;10(8):1127-33.

Follow-up within 2-12 weeks after CIED placement was independently associated with improved survival but increased cardiovascular readmission. Quality improvement initiatives designed to increase adherence to experts' recommendations may be warranted.

Remote monitoring and follow-up of pacemakers and implantable cardioverter defibrillators.
Burri H, Senouf D. Europace 2009;11:701-9. (available online free)

This article gives a general overview of the current status of managing device patients using remote monitoring technology.

Pathophysiology, clinical course and management of congenital complete atrioventricular block.
Bordachar P, Whinnett Z, Ploux S, Labrousse L, Haissaguerre M, Thambo JB.
Heart Rhythm. 2012 Dec 28.

Detailed summary of congenital compete atrioventricular block, focusing on the problem in the absence of structural heart disease. This review leads us through the entity from the pathophysiology to future implications.

Method of pacing does not affect the recurrence of syncope in carotid sinus syndrome.
McLeod CJ, Trusty JM, Jenkins SM, Rea RF, Cha YM, Espinosa RA, Friedman PA, Hayes DL, Shen WK.
Pacing Clin Electrophysiol. 2012 Jul;35(7):827-33. Epub 2012 May 1.

This is a well planned study, which tries to find the suitable pacing mode in cardio-inhibitory CSS. The result could not demonstrate an incremental benefit between VVI, DDDR or DDDR with sudden bradycardia response algorithm. The major limitation of this study is the low number of enrolled patients.

Optimizing pacemaker longevity with pacing mode and settings programming: results from a pacemaker multicenter registry.
Benkemoun H, Sacrez J, Lagrange P, Amiel A, Prakash A, Himmrich E, Aimè E, Mairesse GH, Guénon C,   Sbragia P
Pacing Clin Electrophysiol. 2012 Apr;35(4):403-8. Epub 2012 Feb 6.

This study provides evidence that the reprogramming of dual chamber pacemakers increase the expected longevities. The parameters associated with the major increase in mean longevity were the mode and the atrial and ventricular amplitudes. The SafeR mode (designed to minimize unnecessary ventricular pacing) was associated with a significantly higher expected longevity than the conventional DDD and DDD/AMC (AV delay hysteresis algorithm).

Heart failure in patients with sick sinus syndrome treated with single lead atrial or dual-chamber pacing: no association with pacing mode or right ventricular pacing site.

Riahi S, Nielsen JC, Hjortshøj S, Thomsen PE, Højberg S, Møller M, Dalsgaard D, Nielsen T, Asklund M, Friis EV, Christensen PD, Simonsen EH, Eriksen UH, Jensen GV, Svendsen JH, Toff WD, Healey JS, Andersen HR; DANPACE Investigators.
Europace. 2012 Oct;14(10):1475-82. Epub 2012 Mar 23.

This large randomized study (N=1415) did not find any difference in the development of HF between AAIR and DDDR (with moderately prolonged AVI) pacing modes in patients with SSS. A significant association between HF and right ventricular pacing site (apical vs. non-apical) disappeared with adjustments for baseline variables. Further, the study did not find any association between %VP and development of HF. These findings suggest that DDDR pacing is safe in patients with SSS without increasing the risk of HF.
Limitations of the study: Echocardiography was only performed at enrolment in the trial. Therefore, diagnosis of HF in the present study rests on symptoms and medication.

Adverse effects of long-term right ventricular apical pacing and identification of patients at risk of atrial fibrillation and heart failure.
De Sisti A, Márquez MF, Tonet J, Bonny A, Frank R, Hidden-Lucet F.
Pacing Clin Electrophysiol. 2012 Aug;35(8):1035-43. Epub 2012 Mar 27.

This is a review of the literature on adverse effects of long-term RV apical pacing. The conclusion shows a positive effect of minimal or absent RV pacing which is mainly evident in terms of AFib burden, while there is limited evidence in terms of HF and mortality reduction. In patients with an ICD indication and low LVEF, the negative effects of RV pacing on cardiac performance and survival are more evident. However, some data suggest that avoiding RV pacing may also not be the best option for patients requiring ICD. In patients with impaired LV function, AV synchrony should therefore be ensured. The best pacing mode in ICD patients with HF should be defined on an individual basis.

A comparison of single-lead atrial pacing with dual-chamber pacing in sick sinus syndrome.
Nielsen JC, Thomsen PE, Højberg S, Møller M, Vesterlund T, Dalsgaard D, Mortensen LS, Nielsen T, Asklund M, Friis EV, Christensen PD, Simonsen EH, Eriksen UH, Jensen GV, Svendsen JH, Toff WD, Healey JS, Andersen HR; DANPACE Investigators.
Eur Heart J. 2011 Mar;32(6):686-96. Epub 2011 Feb 7.

A large (N=1415) multicenter study among patients with sick sinus syndrome. The current study is the first large trial to demonstrate that some degree of ventricular pacing in DDDR mode, has no adverse effect on survival in patients with SSS. In patients with SSS, there is no statistically significant difference in death from any cause between AAIR pacing and DDDR pacing programmed with a moderately prolonged atrioventricular interval. AAIR pacing is associated with a higher incidence of paroxysmal atrial fibrillation and a two-fold increased risk of pacemaker reoperation. These findings support the routine use of DDDR pacing in these patients.

Subclinical atrial fibrillation and the risk of stroke.
Healey et al. N Engl J Med 2012;366:120-9.

This report of the ASSERT study evaluated 2580 patients without a history of atrial fibrillation implanted with a dual chamber pacemaker or ICD. Over a 3 month monitoring period, 10% of the patients experienced subclinical atrial tachyarrhythmias (>190bpm during >6min). After a mean follow-up of 2.5 years, subclinical atrial tachyarrhythmias were associated with an increased risk of clinical atrial fibrillation (hazard ratio, 5.56; 95% confidence Interval [CI], 3.78 to 8.17; P<0.001) and of ischemic stroke or systemic embolism (hazard ratio, 2.49; 95% CI, 1.28 to 4.85; P = 0.007). When the analysis included all episodes of atrial tachyarrhythmia detected by devices during the follow-up period, patients were stratified in quartiles according to the duration of the longest episode. The first three quartiles (<17.7 hours) had a rate of stroke or systemic embolism of approximately 1%, whereas the last quartile (>17.7 hours) had a rate of approximately 5%. Continuous atrial overdrive pacing did not prevent atrial fibrillation in this study.

Prospective randomised trial of atrial versus ventricular pacing in sick-sinus syndrome. Andersen HR, Thuesen L, Bagger JP, Vesterlund T, Thomsen PE. Lancet 1994;344:1523-1528.

Landmark first prospective randomised trial of AAI- vs. VVI-pacing in patients with sick sinus syndrome, showing lower frequencies of atrial fibrillation and thromboembolic complications in the AAI-paced group after a mean follow-up of 3.3 years.

Long-term follow-up of patients from a randomised trial of atrial versus ventricular pacing for sick-sinus syndrome.
Andersen HR, Nielsen JC, Thomsen PE, Thuesen L, Mortensen PT, Vesterlund T, Pedersen AK. Lancet 1997;350:1210-1216.

Extension of follow-up in the same patient group (up to 8 years), showing that atrial pacing was significantly associated with freedom from thromboembolic events and survival from cardiovascular death.

Effects of physiologic pacing versus ventricular pacing on the risk of stroke and death due to cardiovascular causes. Canadian Trial of Physiologic Pacing Investigators.
Connolly SJ, Kerr CR, Gent M, Roberts RS, Yusuf S, Gillis AM, Sami MH, Talajic M, Tang AS, Klein GJ, Lau C, Newman DM. N Engl J Med 2000;342:1385-1391.

Large ‘CTOPP’ trial in 2568 patients scheduled for a first implantation of a pacemaker to treat symptomatic bradycardia, randomly assigned to VVI or DDD pacing. After a mean follow-up of 3 years, physiologic pacing provided little benefit over ventricular pacing for the prevention of stroke or death due to cardiovascular causes.

Ventricular pacing or dual-chamber pacing for sinus-node dysfunction.
Lamas GA, Lee KL, Sweeney MO, Silverman R, Leon A, Yee R, Marinchak RA, Flaker G, Schron E, Orav EJ, Hellkamp AS, Greer S, McAnulty J, Ellenbogen K, Ehlert F, Freedman RA, Estes NA, 3rd, Greenspon A, Goldman L. N Engl J Med 2002;346:1854-1862.

A total of 2010 patients with sinus-node dysfunction were randomized in the ‘MOST’ trial to DDD (n=1014) or VVI pacing (n=996) and followed for a median of 33.1 months. Dual-chamber pacing did not improve stroke-free survival but reduced the risk of atrial fibrillation and heart failure, and slightly improved quality of life.

Single-chamber versus dual-chamber pacing for high-grade atrioventricular block.
Toff WD, Camm AJ, Skehan JD. N Engl J Med 2005;353:145-155.

‘UK-PACE’ study in 2021 elderly patients (≥70y) with a pacing indication due to atrioventricular block that dual-chamber cardiac pacing did not reduce mortality from all causes (median follow-up 4.6 years) nor of atrial fibrillation, heart failure, or a composite of stroke, transient ischemic attack, or other thromboembolism (median follow-up 3 years).

Cardiovascular outcomes with atrial-based pacing compared with ventricular pacing: meta-analysis of randomized trials, using individual patient data.
Healey JS, Toff WD, Lamas GA, Andersen HR, Thorpe KE, Ellenbogen KA, Lee KL, Skene AM, Schron EB, Skehan JD, Goldman L, Roberts RS, Camm AJ, Yusuf S, Connolly SJ. Circulation 2006;114:11-17.

Meta-analysis of 5 randomized, controlled, parallel design trials comparing atrial-based pacing with ventricular-based pacing in patients with bradycardia of which individual patient data were available (Danish, PASE, CTOPP, MOST, UKPACE: see also above). Analysis showed no significant reduction in mortality (hazard ratio [HR], 0.95; 95% confidence interval [CI], 0.87 to 1.03; P=0.19) or heart failure (HR, 0.89; 95% CI, 0.77 to 1.03; P=0.15) with atrial-based pacing. There was however a significant reduction in atrial fibrillation (HR, 0.80; 95% CI, 0.72 to 0.89; P=0.00003) and a reduction in stroke that was of borderline significance (HR, 0.81; 95% CI, 0.67 to 0.99; P=0.035). There was no convincing evidence that any patient subgroup received special benefit from atrial-based pacing.

Efficacy of Antibiotic Prophylaxis Before the Implantation of Pacemakers and Cardioverter-Defibrillators: Results of a Large, Prospective, Randomized, Double-Blinded, Placebo-Controlled Trial.
de Oliveira JC, Martinelli M, Nishioka SADO, Varejao T, Uipe D, Pedrosa AAA, Costa R, Danik SB. Circ Arrhythmia Electrophysiol 2009;2:29-34.

Although routinely administered, definitive evidence for the benefits of prophylactic antibiotics before the implantation of permanent pacemakers and implantable cardioverter-defibrillators from a large double-blinded placebo-controlled trial is lacking. This double blinded study included 1000 consecutive patients who presented for primary device (pacemaker or ICD) implantation or generator replacement randomized in a 1:1 fashion to prophylactic antibiotics or placebo. Intravenous administration of 1 g of cefazolin (group I) or placebo (group 2) was done immediately before the procedure. Follow-up was performed 10 days, 1, 3, and 6 months after discharge. The safety committee interrupted the trial after 649 patients were enrolled due to a significant difference in favor of the antibiotic arm (group I: 2 of 314 infected patients--0.63%; group II: 11 of 335 to 3.28%; RR=0.19; P=0.016). Multivariable analysis identified nonuse of antibiotic (P=0.037) and postoperative hematoma (P=0.023) as independent predictors of infection.