Discussion

We examined the temporal trends in the FC and the relationship between the FC and prognosis in patients receiving an initial pacemaker implantation. The major findings of this study were that (1) 43% of the patients with a poor or moderate FC improved to a good FC 3 months after the pacemaker implantation, (2) a poor FC was an independent predictor of both a hospitalization and the total mortality, and (3) the lack of an improvement in the FC at 1 year after the pacemaker implantation was associated with an increased risk of mortality.
It is well established that the exercise capacity, daily physical activity, and daily walking performance are significantly associated with the clinical outcome. 9-11 Recent studies using pacemaker built-in accelerometers found a significant correlation between the physical activity and mortality. Tyagi et al. assessed the physical activity measured by a pacemaker accelerometer in de novo pacemaker implantation patients who had a preserved left ventricular function. 12 They classified the patients into 4 groups based on the average active time and followed them for an average of 4.1 years. The rate of the all-cause mortality significantly increased as the active minutes decreased. Patients with an average of <1 h/day of active time had a nearly 7.5-fold increased risk of death compared to those who were active >3 h/day. In another study, Conraads et al. showed a significant relationship between the physical activity and the mortality in patients with implantable cardioverter defibrillators (ICDs) and reduced the left ventricular ejection fraction. The patients in the lowest tertile for daily activity (<146 min/day) had a 5 times higher risk of mortality compared to those in the highest tertile for daily activity (>235 min/day). 13 These data suggested that the device-measured physical activity may have served as a marker for the unmeasured factors contributing to the mortality risk. In addition, a novel chronotropic incompetence measure (Heart Rate Score) also predicts a worse outcome in patients that undergo device implantations.14, 15 Furthermore, Richards et al. suggested that a blended sensor with minute ventilation and an accelerometer improves the Heart Rate Score in patients with pacemakers. 16 While these device built-in objective indicators may be useful to quantify an individual’s activity, this device software has difficulty in interpreting because the measurement method and calculation method differ depending on the manufacturer. Additionally, device interrogation or remote monitoring are required to use these indicators. On the other hand, a subjective FC by a questionnaire, not a device-measured physical activity, is easily obtainable and is able to predict the outcome.
In this study we showed that 43% of the patients with a poor or moderate FC at the time of the pacemaker implantation had an improved FC 3 months after the implantation and an improved FC was associated with a better outcome. Previous studies showed that the device-measured physical activity increased over a 30-day period after the implantation in patients that received an ICD or cardiac resynchronization therapy defibrillator. 13 That observation was consistent with our study, in that a most of the patients had an improved FC probably because the bradycardia-associated symptoms were alleviated by the pacemaker. Fleischmann et al. demonstrated that the pacemaker implantation itself was associated with a significant improvement in the health-related quality of life (QOL) scores. This improvement extended to almost all domains such as the physical function, physical role, social function, mental health, and vitality. 17Importantly, a QOL improvement was similarly observed irrespective of the sex, presence of heart failure, or comorbidity level. We suspected that the improved QOL with the pacemaker implantation may also have influenced the subsequent prognosis in the present study.
To preserve or improve the physical activity after the permanent pacemaker implantation, physiological pacing is expected to be a promising strategy. Minimizing any inadvertent ventricular pacing is important for maintaining the exercise capacity and preventing subsequent cardiac events. A more physiological pacing such as His-bundle pacing 18is a promising option. Among patients with left ventricular (LV) systolic dysfunction and a wide QRS complex or with ventricular pacing dependency, cardiac resynchronization therapy may be a better device to improve the exercise tolerance. An improvement in the hemodynamic profile and sympatho-inhibitory effect lead to a reversal of skeletal myopathy and an enhanced exercise performance. Cardiac resynchronization increases the LV contractility and reduces functional mitral regurgitation, resulting in an increased cardiac output and dp/dt index. These improvements in the cardiac hemodynamics result in a decrease in the muscle sympathetic nerve activity, reversal of muscle inflammation, and improve the long-term skeletal myopathy. 19
Our study showed that physical inactivity was associated with a poor survival independent of other risk factors. Cardiologists should pay attention not only to the device condition but also to encourage increased physical activity and to follow the patient compliance with physical activity recommendations. Considering the association between significantly reduced physical activity and a poor prognosis, individuals with an FC of <2 METs were stratified into serious conditions and required careful observation. In the majority of patients, the FC improved at 3 months after the pacemaker implantation and was maintained for at least 1 year. Patients with an improved FC at 1 year after the pacemaker implantation had a relatively good prognosis. Particularly, no patients died in the group with an improved FC (METs> 4). Thus, a reevaluation of the physical disability between 3 months and one year may be suitable in patients who have undergone a pacemaker implantation.

Study Limitations

Our study included heterogenous patients receiving pacemakers for atrioventricular block, sick sinus syndrome, and atrial fibrillation with a slow ventricular response. We did not investigate the detailed pacemaker pacing mode, pacing rate, heart rate distribution (i.e., Heart Rate Score), or pacing site, therefore, the relationship between the pacemaker settings and physical activity could not be examined. However, irrespective of the device status, a poor FC was proven to be useful as a prognostic indicator. The conventional prognostic clinical tests such as the B-type natriuretic peptide, renal function, echocardiographic findings, and cardiopulmonary exercise testing were not analyzed. This study did not include the currently available leadless pacemakers.

Conclusions

The pacemaker implantation improved the FC in 43% of the patients with a poor or moderate FC at baseline and remained at that level to the end of 1 year. The poor FC (<2 METs) at baseline was significantly associated with a worse outcome. The patients whose FC improved at 1 year after the pacemaker implantation had a relatively good prognosis.