Abstract

Aims

The OPTI-MIND study aims to collect 2-year clinical outcomes of pacemaker patients in real-world clinical practice, overall and according to patient characteristics and pacemaker settings.

Methods and results

The present analysis of the OPTI-MIND study describes the programmed device settings after discharge from the pacemaker implant. The objective was to determine whether these settings fit recent guidelines for device-programmed physiological pacing based on the preservation of atrioventricular synchrony, avoiding unnecessary pacing, ensuring rate increase during exercise or preventing neurally mediated symptoms. A total of 1740 patients were enroled at 68 centres worldwide. Baseline patient characteristics and device programming settings are available in 1674 of 1740 patients (96%). Guidelines to ensure physiological pacing were followed in 41% of patients: in patients with sinus node disease (SND), and without atrioventricular block (AVB), device programming could have led to unnecessary right ventricular pacing in 38% of patients. In SND patients with chronotropic incompetence, assisted rate increase during exercise was not programmed in 42% of patients. In 11% of patients with AVB, atrioventricular (AV) synchrony was not pursued; the main drivers being advanced age and history of atrial fibrillation. Patients with both SND and AVB were generally programmed physiologically (87%).

Conclusion

The present analysis showed that frequent deviations occurred when comparing the device settings at discharge from the pacemaker implant in clinical practice to the available guidelines on pacing mode selection. Analysis of 2-year outcomes in the OPTI-MIND study will provide an insight into whether specific physiological settings could improve the quality of pacing with a positive effect on patient outcome.

What's new?

  • Pacemaker technology is underused in about half of the recipients.

  • Disease specific-programming was missed in 40% of patients.

  • Enhanced pacemaker automaticity and predifined disease-specific settings that can be stored in the programmer and downloaded to the device can greatly improve tailored pacemaker programming.

Introduction

Cardiac pacing is a well-established treatment for symptomatic bradyarrhythmias. Recently, along with advances in device technology, the goals of permanent pacing have been broadened, aiming to improve the quality of life and decrease cardiovascular morbidity. Research has shown that atrial-based pacing, which promotes physiological pacing, has clinical benefit including reductions in stroke, atrial fibrillation (AF), and embolic risk in selected patients when compared with ventricular pacing.1–9 Physiological pacing has also been shown to enhance pacemaker longevity and cost-effectiveness,10–14 in part, by reducing complications related to upgrades or exchanges.15,16

Modern pacemakers are designed with a variety of programmable settings to tailor physiological pacing to patient needs. However, this device technology is often underused as these settings are commonly not tailored to the patient by the implanting physicians.17 In fact, up to 80% of devices are left at nominal settings post-procedure and only 12% are reported to be reprogrammed at long-term follow-up.14,18

The pacemaker population appears to be shifting without changes in the indications for pacemaker implantation. For example, the mean age of patients receiving pacemakers has been increasing over the past decade.19 To treat patients in a better manner, it is important to understand how and why devices are selected and programmed. The OPTI-MIND study was designed to collect data from patients implanted with a pacemaker under current clinical guidelines. OPTI-MIND will examine outcomes by relevant patient characteristics, underlying disease, pacemaker choice, and programming.

This analysis examined programmed pacemaker settings at discharge from implant to determine if, based on the specific patient rhythm disease, the settings were programmed to achieve physiological pacing according to the recent guidelines.20 Differences between patients who fit or deviate from the recommended pacing guidelines are analysed.

Methods

OPTI-MIND study design

OPTI-MIND (Clinical Outcome of Pacemaker paTIents according to pacing Modality and primary INDications; ClinicalTrials.gov Identifier: NCT00976482) is an observational, prospective, multicentre, single-arm cohort study. OPTI-MIND aims to collect mid-term clinical outcomes according to real-world clinical practice in a group of patients implanted with a permanent pacemaker. The pacemakers implanted in this study are ALTRUA™ models (Boston Scientific). All the devices and algorithms included in this study are CE-marked and approved for general market release in the participating countries and are used under the approved indication. Any compatible and commercially available pacing leads could have been used.

Patients are selected from the investigator's general patient pacemaker implant population. Each patient is followed for a period of 2 years after enrolment according to the schedule and standard practice at the enroling centre. No additional visits or tests are required for participating patients. Patient enrolment occurred within 15 days post-implantation of the current device, after the patient signed the Patient Informed Consent form. The study complies with the Declaration of Helsinki and the research protocol was approved by each locally appointed ethics committee, as applicable. Inclusion criteria are defined as patients ≥18 years of age implanted with current pacemakers, who are willing and capable of providing informed consent, and participating in all the testing associated with this clinical investigation. Exclusion criteria include the inability to be monitored by the participating centres for a period of 2 years; implantation >15 days prior; women of childbearing potential who are, or are planning to become, pregnant during the time of the study; and patients who are currently enroled in another investigational study or registry that directly interferes with the current study.

The present analysis is focused on data collected at enrolment, within 15 days after pacemaker implant, and describes both patient and device programming characteristics to determine whether specific device settings in different classes of patients ensure physiological pacing. The programmable device parameters, which produce physiological pacing have to meet one or more of the following, as dictated by the patient's rhythm: (i) maintenance of atrioventricular (AV) synchrony along the whole spectrum of patient heart rates; (ii) avoidance of unnecessary ventricular pacing in the absence of advanced atrioventricular block (AVB); (iii) avoidance of unnecessary atrial stimulation in the range 40–150 b.p.m. in the absence of sinus node disease (SND); (iv) rate increase during exercise, with rate-responsiveness activated when required in the case of chronotropic incompetence (CI); and (v) avoidance of hypotension-related symptoms in the setting of neurally mediated syndromes (NMSs).

Clinical endpoints

The present analysis is performed only on baseline data from the cohort of patients enroled into the OPTI-MIND study. This study will collect and analyse follow-up data at 2 years after implant. The primary endpoint of the OPTI-MIND study is 2-year all-cause mortality. Secondary endpoints include cardiac mortality or first cardiac-related hospitalization, all-cause hospitalizations, development of indications to implantable cardioverter-defibrillator (ICD), or cardiac resynchronization device (CRT); device upgrade to ICD or CRT; and the 2-year incidence of documented atrial tachycardia or fibrillation in the subgroup of patients without AF as primary rhythm disease at enrolment. At 2 years, mortality and other clinical outcomes will be stratified as a function of specific baseline patient characteristics, primary indication for pacing, chosen pacing modality, and device programming.

Statistical methods

Descriptive statistics are used to describe and summarize the data collected in this clinical study. For continuous variables, mean, standard deviation, and ranges are given. The default P value for comparing two proportions is from the χ2 test. Fisher's exact test is used when one or both of the following occur: the total number of samples is ≤40 and/or at least one cell count in the 2 × 2 table has an expected value <5.

Results

Patient data

A total of 1740 patients were enroled at 68 centres worldwide (Figure 1). Enrolment was complete in June 2011 and baseline patient and device programming characteristics are fully available in 1674 of 1740 patients (96%). Baseline patient characteristics are shown in Table 1. Overall, the mean age of the patients was 76 years and 60% were male (Table 1). In nearly 50% of patients, the primary indication for permanent pacing was AVB (n = 810), sinus node dysfunction was the cause in 32% (SND; n = 538), permanent AF with AVB or slow ventricular rate in 16% (AF; n = 264), and 4% had NMSs (NM; n = 62) (Table 1). Maintenance of AV synchrony by the use of DDD/R devices occurred in 1227 of 1410 patients (87%, Table 2), but was neglected in 83 of 538 (15%) patients with SND, and in 91 of 810 (11%) of patients with AVB. Neglect of AV synchrony was associated with age ≥75 in 64of 83 SND patients and in 66of 91 AVB patients; and with paroxysmal AF in 54of 83 SND patients and in 35of 91 AVB patients. A total of 42of 83 SND patients and 24of 91 AVB patients were both of advanced age and had paroxysmal AF; and neither of the two characteristics were observed in 7of 83 SND and in 14of 91 AVB patients, respectively.

Table 1

Baseline characteristics

  Pacing
 
 
 
Physiological (N = 693) Non-physiological (N = 981) Both groups (N = 1674) P valuea 
Age at enrolment 74.57 ± 9.94 (693) 76.32 ± 9.50 (981) 75.60 ± 9.72 (1674) <0.001 
Gender 
 Male 61.9% (429/693) 59.0% (579/981) 60.2% (1008/1674) 0.24 
Primary rhythm disease 
 Sinus node dysfunction 36.2% (251/693) 29.3% (287/981) 32.1% (538/1674) 0.003 
 Atrioventricular block 37.5% (260/693) 56.1% (550/981) 48.4% (810/1674) <0.001 
 Neuro-mediated syndrome 4.9% (34/693) 2.9% (28/981) 3.7% (62/1674) 0.03 
 Permanent atrial fibrillation 21.4% (148/693) 11.8% (116/981) 15.8% (264/1674) <0.001 
Additional rhythm disease 
 Paroxysmal, persistent, or recurrent AF 41.8% (290/693) 34.9% (342/981) 37.8% (632/1674) 0.004 
 Chronotropic incompetence 20.9% (145/693) 24.7% (242/980) 23.1% (387/1673) 0.0716 
Aetiology 
 No disease 67.2% (466/693) 65.6% (644/981) 66.3% (1110/1674) 0.50 
 Congenital heart disease 0.6% (4/693) 0.7% (7/981) 0.7% (11/1674) >0.99* 
 Hypertrophic cardiomyopathy 2.2% (15/693) 2.4% (24/981) 2.3% (39/1674) 0.71 
 Idiopathic cardiomyopathy 2.9% (20/693) 2.4% (24/981) 2.6% (44/1674) 0.58 
 Infiltrative disease 0.7% (5/693) 1.3% (13/981) 1.1% (18/1674) 0.24 
 Ischaemic cardiomyopathy 18.8% (130/693) 19.6% (192/981) 19.2% (322/1674) 0.68 
 Neuromuscular disease 0.6% (4/693) 0.3% (3/981) 0.4% (7/1674) 0.46* 
 Valvular cardiomyopathy 7.1% (49/693) 7.5% (74/981) 7.3% (123/1674) 0.72 
Associated disease and risk factors 
 None 15.2% (105/693) 15.4% (151/981) 15.3% (256/1674) 0.90 
 Hypertension 73.6% (510/693) 73.3% (719/981) 73.4% (1229/1674) 0.89 
 Diabetes 22.8% (158/693) 25.8% (253/981) 24.6% (411/1674) 0.16 
 Renal disease 11.3% (78/693) 9.7% (95/981) 10.3% (173/1674) 0.30 
 Chronic pulmonary disease 10.1% (70/693) 8.9% (87/981) 9.4% (157/1674) 0.40 
 Peripheral vascular disease 6.6% (46/693) 5.8% (57/981) 6.2% (103/1674) 0.49 
 Other known malignancies 7.1% (49/693) 4.8% (47/981) 5.7% (96/1674) 0.048 
 Other chronic diseases 22.7% (157/693) 21.3% (209/981) 21.9% (366/1674) 0.51 
Other medical history 
 Previous stroke 10.1% (68/673) 8.0% (77/966) 8.8% (145/1639) 0.13 
 Previous MI 14.6% (99/677) 13.1% (127/968) 13.7% (226/1645) 0.38 
 Previous hospitalization for HF 7.3% (48/661) 7.8% (74/953) 7.6% (122/1614) 0.71 
 Previous ablation 3.8% (26/688) 3.1% (30/979) 3.4% (56/1667) 0.43 
LVEFb 
 Compromised (<35%) 1.6% (11/693) 1.5% (15/981) 1.6% (26/1674) 0.92 
 Partially compromised (35–50%) 9.2% (64/693) 9.2% (90/981) 9.2% (154/1674) 0.97 
 Preserved (>50%) 54.7% (379/693) 55.1% (541/981) 55.0% (920/1674) 0.85 
 Not applicable 34.5% (239/693) 34.1% (335/981) 34.3% (574/1674) 0.89 
NYHA functional classb 
 Non-HF subjects 39.4% (273/693) 33.8% (332/981) 36.1% (605/1674) 0.02 
 Class I 20.8% (144/693) 20.6% (202/981) 20.7% (346/1674) 0.93 
 Class II 28.7% (199/693) 31.5% (309/981) 30.3% (508/1674) 0.22 
 Class III 5.2% (36/693) 5.0% (49/981) 5.1% (85/1674) 0.85 
 Class IV 0.4% (3/693) 0.2% (2/981) 0.3% (5/1674) 0.41* 
 Not applicable 5.5% (38/693) 8.9% (87/981) 7.5% (125/1674) 0.01 
  Pacing
 
 
 
Physiological (N = 693) Non-physiological (N = 981) Both groups (N = 1674) P valuea 
Age at enrolment 74.57 ± 9.94 (693) 76.32 ± 9.50 (981) 75.60 ± 9.72 (1674) <0.001 
Gender 
 Male 61.9% (429/693) 59.0% (579/981) 60.2% (1008/1674) 0.24 
Primary rhythm disease 
 Sinus node dysfunction 36.2% (251/693) 29.3% (287/981) 32.1% (538/1674) 0.003 
 Atrioventricular block 37.5% (260/693) 56.1% (550/981) 48.4% (810/1674) <0.001 
 Neuro-mediated syndrome 4.9% (34/693) 2.9% (28/981) 3.7% (62/1674) 0.03 
 Permanent atrial fibrillation 21.4% (148/693) 11.8% (116/981) 15.8% (264/1674) <0.001 
Additional rhythm disease 
 Paroxysmal, persistent, or recurrent AF 41.8% (290/693) 34.9% (342/981) 37.8% (632/1674) 0.004 
 Chronotropic incompetence 20.9% (145/693) 24.7% (242/980) 23.1% (387/1673) 0.0716 
Aetiology 
 No disease 67.2% (466/693) 65.6% (644/981) 66.3% (1110/1674) 0.50 
 Congenital heart disease 0.6% (4/693) 0.7% (7/981) 0.7% (11/1674) >0.99* 
 Hypertrophic cardiomyopathy 2.2% (15/693) 2.4% (24/981) 2.3% (39/1674) 0.71 
 Idiopathic cardiomyopathy 2.9% (20/693) 2.4% (24/981) 2.6% (44/1674) 0.58 
 Infiltrative disease 0.7% (5/693) 1.3% (13/981) 1.1% (18/1674) 0.24 
 Ischaemic cardiomyopathy 18.8% (130/693) 19.6% (192/981) 19.2% (322/1674) 0.68 
 Neuromuscular disease 0.6% (4/693) 0.3% (3/981) 0.4% (7/1674) 0.46* 
 Valvular cardiomyopathy 7.1% (49/693) 7.5% (74/981) 7.3% (123/1674) 0.72 
Associated disease and risk factors 
 None 15.2% (105/693) 15.4% (151/981) 15.3% (256/1674) 0.90 
 Hypertension 73.6% (510/693) 73.3% (719/981) 73.4% (1229/1674) 0.89 
 Diabetes 22.8% (158/693) 25.8% (253/981) 24.6% (411/1674) 0.16 
 Renal disease 11.3% (78/693) 9.7% (95/981) 10.3% (173/1674) 0.30 
 Chronic pulmonary disease 10.1% (70/693) 8.9% (87/981) 9.4% (157/1674) 0.40 
 Peripheral vascular disease 6.6% (46/693) 5.8% (57/981) 6.2% (103/1674) 0.49 
 Other known malignancies 7.1% (49/693) 4.8% (47/981) 5.7% (96/1674) 0.048 
 Other chronic diseases 22.7% (157/693) 21.3% (209/981) 21.9% (366/1674) 0.51 
Other medical history 
 Previous stroke 10.1% (68/673) 8.0% (77/966) 8.8% (145/1639) 0.13 
 Previous MI 14.6% (99/677) 13.1% (127/968) 13.7% (226/1645) 0.38 
 Previous hospitalization for HF 7.3% (48/661) 7.8% (74/953) 7.6% (122/1614) 0.71 
 Previous ablation 3.8% (26/688) 3.1% (30/979) 3.4% (56/1667) 0.43 
LVEFb 
 Compromised (<35%) 1.6% (11/693) 1.5% (15/981) 1.6% (26/1674) 0.92 
 Partially compromised (35–50%) 9.2% (64/693) 9.2% (90/981) 9.2% (154/1674) 0.97 
 Preserved (>50%) 54.7% (379/693) 55.1% (541/981) 55.0% (920/1674) 0.85 
 Not applicable 34.5% (239/693) 34.1% (335/981) 34.3% (574/1674) 0.89 
NYHA functional classb 
 Non-HF subjects 39.4% (273/693) 33.8% (332/981) 36.1% (605/1674) 0.02 
 Class I 20.8% (144/693) 20.6% (202/981) 20.7% (346/1674) 0.93 
 Class II 28.7% (199/693) 31.5% (309/981) 30.3% (508/1674) 0.22 
 Class III 5.2% (36/693) 5.0% (49/981) 5.1% (85/1674) 0.85 
 Class IV 0.4% (3/693) 0.2% (2/981) 0.3% (5/1674) 0.41* 
 Not applicable 5.5% (38/693) 8.9% (87/981) 7.5% (125/1674) 0.01 

aP value from the χ2 test unless noted with an * wherein the Fisher's exact test was used.

bLast measurement within 12 months.

Table 2

Physiological pacing settings

 SND only N = 441 SND + AVB N = 177 AVB only N = 730 Permanent atrial fibrillation N = 264 NM syndrome N = 62 All patients N = 1674 
Physiologically programmed 182 (41%) 126 (71%) 203 (28%) 148 (56%) 34 (55%) 693 (41%) 
Non-physiologically programmed 259 (59%) 51 (29%) 527 (72%) 116 (44%) 28 (45%) 981 (59%) 
Due to       
  No maintenance of AV synchrony 73 (17%) 19 (11%) 82 (28%) n/a 9 (15%) 183 (11%) 
  No avoidance of unnecessary RV stimulation 166 (38%) n/a n/a n/a 12 (19%) 178 (11%) 
  Forced atrial stimulation at normal sinus rates n/a n/a 434 (59%) n/a 6 (10%) 440 (26%) 
  No rate increase during exercise 20 (5%) 32 (18%) 11 (2%) 116 (44%) 1 (2%) 180 (11%) 
 SND only N = 441 SND + AVB N = 177 AVB only N = 730 Permanent atrial fibrillation N = 264 NM syndrome N = 62 All patients N = 1674 
Physiologically programmed 182 (41%) 126 (71%) 203 (28%) 148 (56%) 34 (55%) 693 (41%) 
Non-physiologically programmed 259 (59%) 51 (29%) 527 (72%) 116 (44%) 28 (45%) 981 (59%) 
Due to       
  No maintenance of AV synchrony 73 (17%) 19 (11%) 82 (28%) n/a 9 (15%) 183 (11%) 
  No avoidance of unnecessary RV stimulation 166 (38%) n/a n/a n/a 12 (19%) 178 (11%) 
  Forced atrial stimulation at normal sinus rates n/a n/a 434 (59%) n/a 6 (10%) 440 (26%) 
  No rate increase during exercise 20 (5%) 32 (18%) 11 (2%) 116 (44%) 1 (2%) 180 (11%) 
Figure 1

Patients enrolled by country.

Figure 1

Patients enrolled by country.

Pacing mode and physiological programming across the four rhythm abnormalities requiring pacemaker implantation

Overall, pacemakers in 693 of 1674 (41%) patients were programmed to provide physiological pacing according to the five defined principles: maintenance of AV synchrony, avoidance of unnecessary right ventricular (RV) stimulation in patients without AVB, avoidance of unnecessary atrial stimulation in patients without SND, rate increase during exercise, and avoidance of hypotension-related symptoms. The occurrence of physiological pacing varied with the primary indication for pacing (Table 2, Figure 2). The highest proportion of physiological pacing was observed in patients with combined SND and AVB (71%), the lowest proportion in patients with AVB (28%). Patient baseline characteristics were similar between pacing groups with the following exceptions: non-physiological-paced patients were older but were less likely to have AF and more likely to be diagnosed with heart failure (Table 1). The reasons for non-physiological pacing programming are reported in Table 2.

Figure 2

Percent of enrolled patients with physiologic versus non-physiologic programming according to primary indication for pacing.

Figure 2

Percent of enrolled patients with physiologic versus non-physiologic programming according to primary indication for pacing.

Among 300 patients with declared CI, 137 (46%) did not have rate-responsiveness activated. This was the only reason leading to non-physiological programming in 64 patients; additional reasons for non-physiological programming coexisted in the other 73 patients (Table 2). Grouping patients by the diagnosis of CI and concomitant rhythm disease uncovered additional differences in the proportion of physiological pacing settings (Figures 3A and B). In general, patients with rhythm disease (SND, AVB, or NM) and CI were less likely to receive physiological pacing compared with patients without CI (Figure 3).

Figure 3

Percent of patients receiving physiologic versus non-physiologic pacing in patients with or without chronotropic incompetence. (A) Patients without chronotropic incompetence. (B) Patients with chronotropic incompetence.

Figure 3

Percent of patients receiving physiologic versus non-physiologic pacing in patients with or without chronotropic incompetence. (A) Patients without chronotropic incompetence. (B) Patients with chronotropic incompetence.

Device choice and lead implantation in patients receiving physiological vs. non-physiological pacing

Examining the type of pulse generator implanted, as well as lead polarity and position, revealed differences between patients with and without physiological programming at discharge (Table 3). In both the physiological pacing and the non-physiological pacing groups, the majority of pacemakers prescribed were DR (60%) or SR (21%) (Table 3). Significantly more DDD devices were implanted in patients who then received physiological pacing (14.9 vs. 10.5%, P< 0.01), whereas SSI devices were implanted significantly more often in patients who received non-physiological pacing (0.3 vs. 4.0%, P < 0.01). More right atrial (RA) and RV leads were bipolar in patients programmed with physiological pacing settings. More RA leads were placed in the right atrial appendage (RAA) than any other location in both groups; significantly more subjects with an RA lead implanted in the RAA received physiological pacing. Three-quarters of the RV leads were implanted in the apex; those patients receiving physiological pacing were significantly more likely to have their RV lead in the low-to-mid septal area.

Table 3

Device choice

  Pacing
 
 
 
Physiological (N = 693) Non-physiological (N = 981) Both groups (N = 1674) P value 
Active pulse generator model type 
 DR 60.9% (422/693) 59.4% (583/981) 60.0% (1005/1674) 0.55 
 SR 19.2% (133/693) 22.9% (225/981) 21.4% (358/1674) 0.07 
 DDD 16.0% (111/693) 9.6% (94/981) 12.2% (205/1674) <0.001 
 SSI 0.3% (2/693) 4.1% (40/981) 2.5% (42/1674) <0.001 
 VDD 3.6% (25/693) 4.0% (39/981) 3.8% (64/1674) 0.70 
Lead polarity 
 RA lead     
  Unipolar 1.5% (8/536) 1.5% (10/681) 1.5% (18/1217) 0.97 
  Bipolar 97.0% (520/536) 95.3% (649/681) 96.1% (1169/1217) 0.13 
  Unknown 1.5% (8/536) 3.2% (22/681) 2.5% (30/1217) 0.05 
 RV lead     
  Unipolar 2.8% (19/688) 2.8% (27/977) 2.8% (46/1665) >0.99 
  Bipolar 95.6% (658/688) 94.0% (918/977) 94.7% (1576/1665) 0.13 
  Unknown 1.6% (11/688) 3.3% (32/977) 2.6% (43/1665) 0.03 
RA lead position 
 Right atrial appendage 83.4% (447/536) 76.9% (523/680) 79.8% (970/1216) 0.005 
 Septal wall 1.7% (9/536) 2.1% (14/680) 1.9% (23/1216) 0.63 
 Lateral wall 5.6% (30/536) 8.7% (59/680) 7.3% (89/1216) 0.04 
 Unknown 9.3% (50/536) 12.4% (84/680) 11.0% (134/1216) 0.09 
RV lead position 
 Apex 72.4% (498/688) 79.2% (774/977) 76.4% (1272/1665) 0.001 
 Septal (low to mid) 15.4% (106/688) 8.2% (80/977) 11.2% (186/1665) <0.001 
 Septal (high to RVOT) 3.6% (25/688) 3.3% (32/977) 3.4% (57/1665) 0.69 
 Unknown 8.6% (59/688) 9.3% (91/977) 9.0% (150/1665) 0.60 
  Pacing
 
 
 
Physiological (N = 693) Non-physiological (N = 981) Both groups (N = 1674) P value 
Active pulse generator model type 
 DR 60.9% (422/693) 59.4% (583/981) 60.0% (1005/1674) 0.55 
 SR 19.2% (133/693) 22.9% (225/981) 21.4% (358/1674) 0.07 
 DDD 16.0% (111/693) 9.6% (94/981) 12.2% (205/1674) <0.001 
 SSI 0.3% (2/693) 4.1% (40/981) 2.5% (42/1674) <0.001 
 VDD 3.6% (25/693) 4.0% (39/981) 3.8% (64/1674) 0.70 
Lead polarity 
 RA lead     
  Unipolar 1.5% (8/536) 1.5% (10/681) 1.5% (18/1217) 0.97 
  Bipolar 97.0% (520/536) 95.3% (649/681) 96.1% (1169/1217) 0.13 
  Unknown 1.5% (8/536) 3.2% (22/681) 2.5% (30/1217) 0.05 
 RV lead     
  Unipolar 2.8% (19/688) 2.8% (27/977) 2.8% (46/1665) >0.99 
  Bipolar 95.6% (658/688) 94.0% (918/977) 94.7% (1576/1665) 0.13 
  Unknown 1.6% (11/688) 3.3% (32/977) 2.6% (43/1665) 0.03 
RA lead position 
 Right atrial appendage 83.4% (447/536) 76.9% (523/680) 79.8% (970/1216) 0.005 
 Septal wall 1.7% (9/536) 2.1% (14/680) 1.9% (23/1216) 0.63 
 Lateral wall 5.6% (30/536) 8.7% (59/680) 7.3% (89/1216) 0.04 
 Unknown 9.3% (50/536) 12.4% (84/680) 11.0% (134/1216) 0.09 
RV lead position 
 Apex 72.4% (498/688) 79.2% (774/977) 76.4% (1272/1665) 0.001 
 Septal (low to mid) 15.4% (106/688) 8.2% (80/977) 11.2% (186/1665) <0.001 
 Septal (high to RVOT) 3.6% (25/688) 3.3% (32/977) 3.4% (57/1665) 0.69 
 Unknown 8.6% (59/688) 9.3% (91/977) 9.0% (150/1665) 0.60 

P value from the χ2 test.

The proportion of patients implanted with pulse generators with an available rate-response function is shown in Table 4. In those patients with single sensors, nearly 60% of patients with physiological pacing activated the sensor compared with just over 20% if not (P < 0.01, Table 4). If a dual sensor device was implanted, ∼15% of patients with physiological pacing used both sensors vs. 5% in patients without physiological pacing (P < 0.01, Table 4).

Table 4

Sensor availability

  Pacing
 
 
 
Physiological (N = 693) Non-physiological (N = 981) Both groups (N = 1674) P value 
None (devices without sensors) 16.3% (113/693) 13.7% (134/981) 14.8% (247/1674) 0.13 
Single sensor devices 30.0% (208/693) 31.7% (311/981) 31.0% (519/1674) 0.46 
 Accelerometer ON 57.2% (119/208) 20.9% (65/311) 35.5% (184/519) <0.001 
 Sensor OFF 42.3% (88/208) 79.1% (246/311) 64.4% (334/519) <0.001 
Dual sensors devices 53.7% (372/693) 54.6% (536/981) 54.2% (908/1674) 0.70 
 Dual sensors ON 14.0% (52/372) 4.7% (25/536) 8.5% (77/908) <0.001 
 Accelerometer ON 46.8% (174/372) 28.2% (151/536) 35.8% (325/908) <0.001 
 Both sensors OFF 38.4% (143/372) 66.2% (355/536) 54.8% (498/908) <0.001 
  Pacing
 
 
 
Physiological (N = 693) Non-physiological (N = 981) Both groups (N = 1674) P value 
None (devices without sensors) 16.3% (113/693) 13.7% (134/981) 14.8% (247/1674) 0.13 
Single sensor devices 30.0% (208/693) 31.7% (311/981) 31.0% (519/1674) 0.46 
 Accelerometer ON 57.2% (119/208) 20.9% (65/311) 35.5% (184/519) <0.001 
 Sensor OFF 42.3% (88/208) 79.1% (246/311) 64.4% (334/519) <0.001 
Dual sensors devices 53.7% (372/693) 54.6% (536/981) 54.2% (908/1674) 0.70 
 Dual sensors ON 14.0% (52/372) 4.7% (25/536) 8.5% (77/908) <0.001 
 Accelerometer ON 46.8% (174/372) 28.2% (151/536) 35.8% (325/908) <0.001 
 Both sensors OFF 38.4% (143/372) 66.2% (355/536) 54.8% (498/908) <0.001 

P value from the χ2 test.

Discussion

The OPTI-MIND study aims to collect clinical outcomes of patients implanted with pacemakers in real-world clinical practice. This preliminary analysis gives an insight into the current practice of device selection and pacing mode programming according to the underlying cardiac rhythm abnormality. Based on the available literature and on the recent HRS/ACCF update on device selection and pacing mode programming,20 we defined simple principles to identify physiological programming in the different rhythm diseases: preservation of AV synchrony, avoidance of unnecessary RV stimulation in non-AVB patients, avoidance of unnecessary atrial stimulation at normal sinus rates, rate increase during exercise, and prevention of neurally mediated symptoms. We observed that only 41% of the patients received physiological programming, based on the above-mentioned criteria, and that the differences exist among the specific rhythm diseases. We investigated device programming in this study population with respect to these simple physiological principles to understand how tailored device programming can be achieved.

Sinus node disease

Atrioventricular synchrony was not pursued in 17% of patients. The decision to accept AF as the ultimate rhythm in patients with frequent atrial arrhythmias may be the reason to implant VVIR units. It is more interesting that unnecessary RV pacing was not avoided in 38% of patients without AV block (Table 2), despite compelling evidence to do so.8,21,22 This finding highlights the reluctance to change from shipment programming, with AV delay settings that do not meet SND-specific programming. In these specific cases, the minimum AV delay should be at least longer than the intrinsic AV conduction,21 or the ‘RV stimulation avoidance’ algorithm should be automatically activated to search for spontaneous AV conduction. Rate increase during exercise was not aided by rate-responsiveness in ∼42% of SND patients declared to have CI (Table 2, Figure 2). In the light of the difficult assessment of CI in pacemaker candidates,23,24 we believe that rate-responsiveness should automatically be activated when the sensor input dictates a rate increase up to a physician-programmed value that is not met by the patients' spontaneous activity. Indeed, 79% of dual-chamber pacemakers were rate-responsive in this study; while severely symptomatic patients (maximum heart rate during exercise <80 b.p.m.) benefit from rate-responsiveness, there is little evidence that pacing in the DDDR mode provides any advantage over physiological DDD pacing in unselected pacemaker recipients.25 Although of moderate clinical importance, this feature may significantly improve the quality of life of aged pacemaker recipients who are most likely to receive negative chronotropic drugs and to have heart failure.23,26,27

Atrioventricular block

Atrioventricular synchrony was not pursued in 11% of patients (Table 2); although the main drivers for a VVI/R unit were age ≥75 and history of AF, no reason to neglect AV synchrony was found in 1.7% of patients. This finding is expected, as older patients with a history of AF are less likely to benefit from physiological pacing, especially if not pacemaker-dependent.28 Indeed, this behaviour is also reflected in the recent HRS/ACCF recommendations on device selection and mode programming and 2013 ESC Guidelines on cardiac pacing and cardiac resynchronization therapy.20,29

Shipment programming of dual-chamber units suit AVB patients fairly well; however, forced atrial stimulation at the normal sinus rate in the range 40–60 b.p.m. can cause unnecessary battery depletion and may cause loss of atrial kick due to a non-tailored paced AV delay. The optimal left ventricular filling time is critically dependent on the interatrial conduction time when atrial stimulation is delivered; although frequently neglected in pacemaker recipients, this has been clearly elucidated in CRT recipients.30 Thus, unless symptomatic bradycardia coexists, the lower rate should automatically allow VDD pacing from 40 b.p.m. up to the maximum tracking rate in AVB patients. The lower rate was indeed unchanged from 60 b.p.m. in 59% of AVB patients with normal sinus node function (Table 2).

Coexistent sinus node dysfunction and atrioventricular block

This subgroup of 177 patients highlights very well the attitude of ‘no change from shipment’ as, when there is no CI, nearly 87% of patients were programmed physiologically because the default shipment settings provide coverage for both SND and AVB. In contrast, in the event of declared CI, physiological programming drops to around 50% despite having a DR unit implanted in 89% of this latter group of patients. This means that rate-responsiveness was never turned on in half of the CI patients. This behaviour seems to be in keeping with the Automaticity trial, in that physician-driven reprogramming may not be dictated by clinical evidence, and may be influenced by misleading perceptions.31 This finding confirms that rate-responsiveness should automatically turn on when a mismatch of spontaneous heart rate with sensor-indicated activity occurs in daily-life exercise, to improve patients' quality of life.

Atrial fibrillation patients

Rate increase during exercise was not available in 44% of patients, although 89% of single-chamber pacemakers were rate-responsive and despite the indication of permanent AF with either slow ventricular conduction or AVB. As for the SND patients, when a rate increase is needed, rate-responsiveness should be automatically activated as dictated by patient's activity at the sensor-recommended rate when it is not met by the intrinsic rhythm.

Neurally mediated syndromes

Although prevention of symptoms was achieved by rhythm management, the same proportion of non-physiological pacing as in the SND and the AVB patients also occurred in this subgroup, confirming the general attitude towards pacemaker programming.

Overall, we observed that, with increasing complexity of the underlying rhythm disease, the chance of physiological stimulation increases owing to the shipment setting (that is appropriate for a broad rhythm disease), whereas single rhythm diseases require a specific setting to ensure a physiologically tailored programming. Disappointingly, in the broad real-life scenario put forth in OPTI-MIND, pacemaker programming decreases the chances of receiving physiological programming (Figures 2 and 3, Table 2). Our data highlight the importance of pre-defined disease-specific settings that are either programmable in a single shot after implantation or automatically activated, to ensure physiological pacemaker programming. This possibility is currently offered by some manufacturers, allowing physician-defined settings labelled with specific rhythm diseases (i.e. SSS, AVB, and NMS) to be saved in the programmer software and, thus, programming a device at implantation with a single click. This would obviate the need for the implanting physician to run all the steps of parameter programming and would minimize the possibility of random errors. At the same time, it would make programming time-efficient.

Indeed, we observed in this study that, despite the physicians' awareness of the patients' rhythm disorder being triggered by the participation in the study, tailored physiological programming was missed in more than half the population (Table 2). This is not surprising, since pacemakers are rarely reprogrammed from shipment,18 and the physicians rely on manufacturer-based programmed settings that are rarely updated based on recent studies.5,8,11,21,22,28,31,32 This has been recently confirmed in the Automaticity study, where <5% of devices were reprogrammed at follow-up when all the automatic features were activated soon after implantation,31 uncovering a reluctant physician attitude at device (re)programming. More importantly, about one-third of physician-operated changes were not appropriate for the clinical setting; thus, resulting in random mistakes.31

We believe that this attitude may stem from the presentation format of the pacing parameters in the devices, and from incomplete information about disease-specific programming. Owing to the high reliability of automatic algorithms for stimulation, a disease-specific setting with a clinical presentation format of the pacing parameters would make programming clinically appropriate and efficient in 100% of patients. In the future, pacemakers may themselves automatically programme the most appropriate settings based on information gathered by the device (e.g. the sinus rate and AV conduction) over the first 2–4 weeks after implantation. To further personalize the device settings, the physicians would enter the optimal range of the atrial rate and the longest AV delay for each individual patient to ensure avoidance of unnecessary atrial and ventricular pacing, maintenance of the atrial kick, and appropriate rate increase during exercise.

Conclusion

Physiological pacemaker programming in specific rhythm abnormalities is not met in about 60% of patients. Pre-defined/customized disease-specific settings that are stored in the programmer and could be programmed in a single-shot after implantation would dramatically improve the quality of cardiac stimulation delivered to patients. Programming based on physiologic hints would be more meaningful to clinicians, and may trigger useful programming changes when the predefined settings prove suboptimal. The follow-up of the OPTI-MIND patients, a registry of the real-life paced population, will provide a meaningful insight into the effect of physiological programming related to the five simple principles on patients' outcome.

Study limitations

OPTI-MIND used devices from a single manufacturer (Boston Scientific) and clinical and reprogramming practice patterns may differ with device brand. In addition, although the protocol instructed participating sites to use local, routine clinical practice, differences between sites and countries may affect the patterns of reprogramming. Finally, the number of patients enroled per country varies and could imply a potential bias.

Acknowledgements

The authors thank Kristine Roy, PhD (Boston Scientific Corporation) for assistance in manuscript preparation and Alex Shih (Boston Scientific Corporation) for statistical analysis. This work was supported by Boston Scientific.

Conflict of interest

M.B. declares involvement in educational activity and speaker bureau of Boston Scientific and Medtronic. E.V. is a full-time employee and stockholder of BSC.

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