NCA - Cardiac Pacemakers: Single-Chamber and Dual-Chamber Permanent Cardiac Pacemakers (CAG-00063R3) - Decision Memo

2.Internal technology assessmentConnolly SJ, Kerr CR, Gent M, Roberts RS, Yusuf S, Gillis AM, Sami MH, Talajic M, Tang AS, Klein GJ, Lau C, Newman DM. Effects of physiologic pacing versus ventricular pacing on the risk of stroke and death due to cardiovascular causes. Canadian Trial of Physiologic Pacing Investigators. N Engl J Med. 2000 May 11;342(19):1385-91.Connolly and colleagues reported the results of the Canadian Trial of Physiologic Pacing (CTOPP), a randomized trial that evaluated the benefit of physiologic pacing in patients requiring a pacemaker for symptomatic bradycardia.  Patients were eligible if they were scheduled for an initial implantation of a pacemaker to correct symptomatic bradycardia, did not have chronic atrial fibrillation, and were at least 18 years old.  Exclusion criteria were atrioventricular nodal ablation or life expectancy less than two years.  Primary outcome was the occurrence of either stroke or death due to cardiovascular causes.  Secondary outcomes were death from any cause, documented AF, and congestive heart failure hospitalization.  A total of 1474 patients were randomly assigned to receive a ventricular pacemaker and 1094 to a physiologic pacemaker (dual-chamber, atrial and ventricular).  Mean age at baseline was 73 years.  Men comprised 59 percent of the study population.  AVB was the most common indication for pacing.  Sinoatrial node disease was present in 40 percent of patients.  Mean follow-up was three years.The authors reported: The annual rate of stroke or death due to cardiovascular causes was 5.5 percent with ventricular pacing, as compared with 4.9 percent with physiologic pacing (reduction in relative risk, 9.4 percent; 95 percent confidence interval, 10.5 to 25.7 percent [the negative value indicates an increase in risk]; P = 0.33).  They concluded: Physiologic pacing provides little benefit over ventricular pacing for the prevention of stroke or death due to cardiovascular causes.Fleishmann KE, Orv EJ, Lamas GA, Mangione CM, Schron EB, Lee KL, Goldman I.:  MOST investigators.  Atrial fibrillation and quality of life after pacemaker implantation for sick sinus syndrome; data from the Mode Selection Trial (MOST).  Am Heart J.  2009 Jul;158(1):78-83.e2.doi: 10.1016/j.ahj.2009.02.023.Fleischmann and colleagues reported the results of a specific analysis of QOL as a pre-specified secondary outcome of the Mode Selection Trial (MOST; see primary results reported by Lamas, 2002).  QOL was measured with the Medical Outcomes Study 36-Item Short Form (SF-36) General Health Survey at baseline, three months, 12 months, 24 months, 36 months, and 48 months.  The investigators found that [p]acemaker implantation resulted in substantial improvement in almost all QOL measures but [s]ubjects 75 years or older experienced significantly less improvement in functional status and physical component summary scores than did younger subjects.  They concluded: Pacemaker implantation improved health-related QOL.  The mode selected was associated with much smaller, but significant, improvements in several domains, particularly role physical function.Fored CM, Granath F, Gadler F, Blomqvist P, Rynder J, Linde C, Ekbom A, Rosenqvist M. Atrial vs. dual-chamber cardiac pacing in sinus node disease: a register-based cohort study. Europace. 2008 Jul;10(7):825-31. doi: 10.1093/europace/eun118. Epub 2008 May 7.Fored and colleagues reported the results of an analysis of a pacemaker registry to compare the incidence of cardiovascular morbidity and mortality in patients with sinus node disease.  Patients who had sinus node disease and received an AAI- or DDD-mode pacemaker implant between 1989 and 2002 and were identified from the Swedish implantable cardioverter defibrillator and pacemaker register (n = 9563).  Patients with a hospital discharge diagnosis of stroke prior to the pacemaker implant were excluded (n = 786).  Primary outcomes were the first hospitalization for, or death from AF or flutter, stroke, or any cardiovascular disease.  Of the 8777 patients in the analysis, 2685 received atrial pacing (AAI; 30.6%) and 6092 received dual chamber pacing (DDD; 69.4%).  Eighty-seven percent of the patients were 60 years or older. Men comprised 47 percent of the cohort.  Mean follow-up was four years for AAI patients and 2.8 years for DDD patients.The authors reported: Patients with DDD pacing and without any pre-implant admission for atrial fibrillation or flutter had an increased risk of post-implant fibrillation or flutter, in relation to corresponding AA[I] patients [hazard ratio (HR) = 1.30; 95% confidence interval (CI) 1.101.52].  A slight increase in the risk of any cardiovascular disease (HR = 1.07; CI, 1.001.15), and all-cause mortality (HR = 1.12; CI, 1.001.25), was seen among DDD patients, in relation to AAI patients, but there was no significant difference in the risk of ischaemic or unspecified stroke (HR = 1.14; CI, 0.941.37).  Among DDD patients, the all-cause mortality did not differ from the general population [standardized mortality ratio (SMR) = 1.04; CI, 0.981.11].  Patients with AAI, however, had a decreased all-cause mortality risk (SMR = 0.89; CI, 0.820.97).  They concluded: Our results support AAI as the preferred mode of pacing in patients with sinus node disease, and a normal AV node function.Kerr CR, Connolly SJ, Abdollah H, Roberts RS, Gent M, Yusuf S, Gillis AM, Tang AS, Talajic M, Klein GJ, Newman DM. Canadian Trial of Physiological Pacing: Effects of physiological pacing during long-term follow-up. Circulation. 2004 Jan 27;109(3):357-62. Epub 2004 Jan 5.Kerr and colleagues reported the results of an extended follow-up analysis of CTOPP, a randomized trial that compared physiological pacing that maintained atrioventricular synchrony (dual-chamber or atrial pacing) compared with ventricular pacing with regard to the composite outcome of cardiovascular death and stroke, reported by Connolly in 2000.  Of the 2568 patients randomized in CTOPP, 1995 were eligible for the extended follow-up study with 94.9 percent follow-up at three years.  The primary outcome was the composite of cardiovascular death or stroke.  Secondary outcomes were overall mortality, stroke, and new development of AF.  Mean follow-up of the combined CTOPP and extended study was 6.4 years.  The authors concluded: The CTOPP extended study does not show a difference in cardiovascular death or stroke, or in total mortality, or in stroke between patients implanted with ventricular or physiological pacemakers over a mean follow-up of 6 years.  However, there is a persistent significant reduction in the development of atrial fibrillation with physiological pacing.Lamas GA, Lee KL, Sweeney MO, Silverman R, Leon A, Yee R, Marinchak RA, Flaker G, Schron E, Orav EJ, Helkamp AS, Greer S, McAnulty J, Elenbogen K, Ehlert F, Freeman RA, Estes NA 3rd, Greenspon A, Goldman L:  Mode Selection Trial in Sinus-Node Dysfunction.  Ventricular pacing or dual-chamber pacing for sinus-node dysfunction.  N Engl J Med. 2002 Jun 13:346(24):1854-62.Lamas and colleagues reported the results of a randomized trial to determine whether dual-chamber pacing would provide better event-free survival and quality of life than single chamber ventricular pacing in patients with sinus-node dysfunction.  Patients aged 21 years and older with SND in sinus rhythm were eligible.  Patients with serious comorbidities (study site determined) were excluded.  Primary outcome was death from any cause or nonfatal stroke.  Prespecified secondary outcomes included cardiovascular mortality, AF and QOL.From September 1995 to October 1999, 2010 patients were enrolled at 91 sites.  All patients received a dual chamber, rate modulated pacemaker but the device programming varied with assignment.  Patients were randomly assigned to dual chamber pacing (n = 1014) or ventricular pacing (n = 996).  Median age was 74 years.  Men comprised 52 percent of the study population.  Median follow-up was 33.1 months.  The investigators found that incidence of the primary end point did not differ significantly between the dual-chamber group (21.5 percent) and the ventricular-paced group (23.0 percent, P = 0.48).  They concluded: In sinus-node dysfunction, dual-chamber pacing does not improve stroke-free survival, as compared with ventricular pacing.  However, dual chamber pacing reduces the risk of atrial fibrillation, reduces signs and symptoms of heart failure, and slightly improves the quality of life.  Overall, dual chamber pacing offers significant improvement as compared with ventricular pacing.Lamas GA, Orav EJ, Stambler BS, Ellenbogen KA, Sgarbossa EB, Huang SK, Marinchak RA, Estes NA 3rd, Mitchell GF, Lieberman EH, Mangione CM, Goldman L. Quality of life and clinical outcomes in elderly patients treated with ventricular pacing as compared with dual-chamber pacing. Pacemaker Selection in the Elderly Investigators. N Engl J Med. 1998 Apr 16;338(16):1097-104.Lamas and colleagues reported the results of a randomized, controlled comparison of ventricular pacing and dual chamber pacing to assess the effect of the pacing mode on the health-related QOL of older adults.  Inclusion criteria were age of 65 years or older, sinus rhythm, and a permanent pacemaker requirement for bradycardia.  Exclusion criteria were inability to participate in the QOL assessments, clinically overt congestive heart failure at the time of implantation, AF without any documented sinus mechanism for more than six months, serious non-cardiac illness, and inadequate atrial-capture or sensing thresholds.  Primary outcome was multidimensional health-related QOL measured with the 36-item Medical Outcomes Study Short-Form General Health Survey (SF-36) at three, nine and 18 months.  Pre-specified secondary end points were death from all causes; first nonfatal stroke or death; first hospitalization for heart failure, first nonfatal stroke, or death; development of atrial fibrillation; and development of the pacemaker syndrome.From February 1993 to September 1994, 407 patients were enrolled at 29 sites.  All patients received dual chamber rate-adaptive pacemakers, but the device programming varied with assignment.  Patients were randomly assigned to single chamber ventricular pacing (n = 204) or dual chamber pacing (n = 203).  Mean age was 76 years.  Men comprised 60 percent of the study population.  The authors reported: Quality of life improved significantly after pacemaker implantation (P < 0.001), but there were no differences between the two pacing modes in either the quality of life or prespecified clinical outcomes (including cardiovascular events or death).  They concluded: The implantation of a permanent pacemaker improves health-related quality of life.  The quality-of-life benefits associated with dual-chamber pacing as compared with ventricular pacing are observed principally in the subgroup of patients with sinus-node dysfunction.Nielsen JC, Kristensen L, Andersen HR, Mortensen PT, Pedersen OL, Pedersen AK. A randomized comparison of atrial and dual-chamber pacing in 177 consecutive patients with sick sinus syndrome: echocardiographic and clinical outcome. J Am Coll Cardiol. 2003 Aug 20;42(4):614-23.Nielsen and colleagues reported the results of a randomized trial to compare single-chamber atrial (AAI) and dual-chamber (DDD) pacing in patients with sick sinus syndrome (SSS).  Inclusion criteria were symptomatic bradycardia < 40 bpm or symptomatic QRS pauses of more than two seconds.  Exclusion criteria included AVB, chronic AF and bundle branch block.  Primary outcomes were changes in left atrial (LA) size and left ventricular (LV) size and function as measured by M-mode echocardiography.  Secondary outcomes included death, stroke and AF.  From December 1994 to March 1999, 177 consecutive patients were randomized to one of three rate-adaptive pacemakers: single chamber atrial (AAIR; n = 54), dual chamber (DDDR-s with a short AV delay; n = 60) or dual chamber (DDDR-l with a fixed long AV delay; n = 63).  Mean age was 75 years.  Men comprised 41 percent of the study population.  Mean follow-up was three years.