Background <p>Exercise training, delivered within a cardiac rehabilitation program, improves both quality of life and clinical outcomes in patients with cardiovascular diseases (CVDs). Assessing heart rate variability (HRV) during training sessions has been shown to assist in tailoring exercise programs and optimizing their therapeutic effects. In this study, we investigated how the discontinuation of the betablocker bisoprolol affects HRV assessed during exercise in CVDs patients.</p> Methods <p>We present a case series of eight CVDs patients, (age: 71.3±5.7; BMI: 27.4±1.8 <InlineEquation ID="IEq1"> <EquationSource Format="TEX">\(\text {kg/m}^2\)</EquationSource> </InlineEquation>), seven male and one female in stable clinical conditions, who performed cycle-ergometer exercise at a constant pedaling cadence. During the exercises: i) the HR (mean over instantaneous HR values) was meaningfully regulated, through a variable control load, to a piecewise constant reference, with the aim of meeting stationarity conditions for a 3-minutes short-term analysis of HRV; ii) the first HR reference value, within each exercise bout, was set close to the HR resting value of the patients, thus making room for the HRV baseline measure. Each patient performed three HR-controlled training bouts, at a non-decreasing rate of perceived exertion, in two different experimental sessions: A) while taking bisoprolol; B) 48-hours after discontinuation of the bisoprolol therapy. HRV recordings were made during all the phases of the bouts in which a constant HR reference was imposed. They led to the evaluation of low frequency (LF) and high frequency (HF) components, all of them normalized with respect to the total power.</p> Results <p>In most phases, the use of bisoprolol non-negatively affects the HR regulation performance. On the other hand, when the analysis, over a proper subset of patients, is restricted to the phases for which a direct comparison – with and without bisoprolol – can be made at the same HR (almost constant) level, it is uniformly observed that: i) normalized HF was higher with bisoprolol in A session than in the B session, ii) normalized LF was lower with bisoprolol (A session) than in the B session, and consequently, iii) the LF/HF ratio is lower with bisoprolol (A session) than in the B session. Such modifications are stronger in a patient whose HR is more largely reduced by the effect of bisoprolol.</p> Conclusions <p>The experimental data of this paper go beyond previous studies showing that betablockers affect HRV (at rest) in patients with CVDs. Indeed, they extend those findings to an HR-controlled exercise framework that is, in our view, feasible and potentially advantageous in the cardiac rehabilitation field, since it provides quantitative variables (namely, the integral of the HR regulation error over the 3-minute-long time window at constant HR reference, as well as the normalized HF, LF, respectively): i) to characterize the HR regulation performance whose accuracy is necessary for measuring the HRV; ii) the subject’s functional response to the training level assessed during the exercise, which might allow for a precision approach to rehabilitation.</p>