The present study used two methods to assess impaired chronotropic response to physical activities in patients with heart failure. The method of traditional treadmill exercise testing identified 50% of patients whose maximal HR during peak exercise failed to reach at least 70% of APMHR, a criterion for CI diagnosis in heart failure patients [12, 19, 20]. Holter-Actigraph recording and corresponding measurements showed a high concordance with the results of exercise testing. Furthermore, in the 24-h recording of HR and physical activities by the Holter-Actigraph system, the assessment of chronotropic response during 6-MHW and daily living found worse chronotropic response in CI patients than in non-CI patients, demonstrating the feasibility of assessment of impaired chronotropic response in heart failure patients by this method.
In the present study, maximal HR during peak exercise failed to reach at least 70% of APMHR in 50% of tested patients, thus CI was diagnosed accordingly for these patients. When HR reserve and chronotropic index-β were used to assess CI, 21 (80.8%) of 26 patients who took exercise testing failed to attain ≥80% of HR reserve and 10 (38.5%) patients failed to attain ≥60% of the chronotropic index-β. Thus, the CI incidence in heart failure population depends on the methods used for diagnosis . The criterion of 70% APMHR was used in the present study, based on which the study found that (1) patients who met the CI diagnosis criterion had a significantly lower HR reserve and chronotropic index-β than those who did not meet the CI diagnosis criterion, and (2) HR changes in response to daily physical activities and the 6MHW distance were significantly smaller in patients who met the CI criterion than those who did not. When compared to the general population who have no heart failure and can reach the target heart rate during exercise testing (e.g., ≥85% APMHR) [7, 8], the heart failure patients in the present study whose heart rate during exercise testing could reach ≥70% APMHR, but still less than 85% might have reduced chronotropic response even though the CI could not be definitively diagnosed.
The present study applied a wearable recording system (Holter-Actigraph) during treadmill exercise testing in heart failure patients and assessed the correlation between treadmill exercise test results and measurements by Holter-Actigraph recording. The rationale to adopt Holter-Actigraph recording was to validate an ease-of-use tool that can be used to screen for and assess CI without the need of special infrastructure like a treadmill exercise test laboratory. The uniqueness of the present study was to use Holter-Actigraph recording to determine HR during physical activities during daily living including 6MHW and thus evaluate chronotropic capacity. The analysis of HR and physical activities based on Holter-Actigraph recording revealed a significant correlation between heart rate and physical activity levels, e.g., chronotropic response. Furthermore, the study found a significant correlation between the 6MHW distance and the percent APMHR achieved during exercise testing and reduced physical activity intensity in patients with impaired chronotropic incompetence. Thus, the Holter-Actigraph system can potentially be used to screen for CI and assess impaired chronotropic response in heart failure patients.
Exercise intolerance and symptoms of dyspnea and fatigue on effort are clinical manifestations in patients with heart failure. It is assumed that the appearance of these symptoms is more likely due to heart failure if rapid heart rate occurs in response to a moderate activity rather than the cause of CI in which there is a lack of a significant increase in heart rate. Thus, heart rate changes in response to a physical activity can be used to distinguish whether symptoms are caused by CI or not.
Recent studies have demonstrated a high incidence of CI in the heart failure population and CI has been recognized as an independent risk factor for cardiovascular morbidity and mortality. Daily exercise is recommended for patients with chronic heart failure. However, the exercise intensity in terms of magnitude and time interval still remains uncertain and the intensity of exercise is significantly influenced by the capability of chronotropic response. Furthermore, use of β-blockers complicates chronotropic response, leading to a reduced chronotropic response [8, 9, 11, 21,22,23]. On the other hand, β-blockers have been a standard therapy that prolongs survival of heart failure patients in several clinical trials [24,25,26]. There are approximately 5.8 million patients with heart failure in the United States and 23 million worldwide . It can be assumed that the majority of heart failure patients would not receive an assessment of their chronotropic response. As shown in the present study, of 40 heart failure patients, 14 (35%) patients who declined treadmill exercise testing did have low %APMHR achieved during 6MHW and daily physical activities. Thus, if a simple, ease-of-use tool can be used to screen for CI and assess impaired chronotropic response in heart failure population, more patients with impaired chronotropic response could be identified and better managed during heart failure treatment including exercise-based cardiac rehabilitation and treatment with β-blockers. Rate-responsive pacing is an effective method to relieve symptoms caused by CI [8, 28]. However, such a therapy may be underutilized in the heart failure population because exercise intolerance-related symptoms are more often recognized as heart failure symptoms instead CI-caused symptoms. Exertional dyspnea and weakness-asthenia are common symptoms in both chronic heart failure and CI. If drug therapy, such as loop diuretics, does not effectively relieve exertion-related symptoms in heart failure patients with CI, rate-responsive pacing can be considered. In addition, CI can be a manifestation of sick sinus dysfunction whose symptoms include dyspnea, asthenia, fatigue, frequent dizziness, and possible fainting or syncope with the potential of precipitating or aggravating a state of heart failure . Thus, rate-responsive pacing can be used if these patients receive a pacemaker. The present study clinically not only confirmed a high CI incidence in heart failure patients, but also investigated the feasibility of using Holter-Actigraph recording as an alternate and simpler tool to identify heart failure patients with CI and impaired chronotropic response. Prospective studies are needed to evaluate clinical benefits that can be provided by the assessment of chronotropic impairment with the use of tools as the Holter-Actigraph recording.
The present study used the symptom-limited maximal exercise test that did not have respiratory monitoring or measurement of peak oxygen consumption. Thus, the present study did not incorporate the information of metabolic and oxygen demand during exercise. Second, the present study had a relatively small sample size and enrolled heart failure patients with LVEF ranging from 35% to 53%. Moreover, exercise intolerance is one of the clinical manifestations of heart failure and use of β-blockers further complicates chronotropic response [8, 11, 21,22,23]. Thus, the variables for determining CI or chronotropic impairment derived from the present study need to be further confirmed in a clinical study with a large population including patients with all levels of LVEF and different medications.