**2. Making the devices smarter**

#### **2.1 Historical glimpse**

The implementation of artificial pacing goes back more than 70 years [6]. The first electrical devices connected to a patient to provide electrical impulses to stimulate the heartbeat in bradycardia cases have been known since the 1950s. Thanks to the invention of silicon transistor in 1956, the 1958 was a remarkable milestone. In winter 1958, engineer Earl Bakken of Minneapolis, USA, co-founder of Medtronic company, produced the first wearable external pacemaker for a patient of C. Walton Lillehei. On October 8, 1958, the first electronic pacemaker was implanted by Senning and Elmqvist in Solna, Sweden. In 1958, Dr. William Chardack teamed up

with engineer Wilson Greatbatch and Dr. Andrew Gage to implant an electrode in a dog attached to a pulse generator. They worked for the next two years to refine their design of a unit. They implanted the pacemaker into a man and commercialized the product in 1960.

All the early pacemakers maintain the same constant pulse rhythm for long periods of time. A pacemaker in demand also appeared in the 1960s, which only paced when stimulation was required (when natural pacing ceased). In addition, the dualchamber pacemaker with synchronized pacing of both atrium and ventricle (known as physiological pacing) was first designed in 1960s [6]. In the end of this period are included also first attempts to use the variable pacing rhythm to adapt it to a physiological need, i.e., the metabolic requirement corresponding to body's work known as rate-responsive pacing [7]. The medical use of rate-responsive pacing began in early 1980s [8].

#### **2.2 Sensing and sensors for the adaptive and closed-loop control of pacing rate**

The problem is: how to get information for the adjusting of pacing rate? Obviously, it is almost impossible to use the body's natural sensing nodes for this purpose; the help of artificial means or sensors is required [7, 8]. Some of the proposed information sources for regulating the pacing rate are oxygen saturation level, venous pH, QT interval, activity of body motions, respiratory rate, minute volume (MV), stroke volume (SV), central venous temperature, peak endocardial acceleration, and electrical impedance changes of the right ventricle (reflects a stroke volume) during the whole cardiac cycle. QT interval (reflecting both physiological and mental status) and minute volume (MV) sensors based on the electrical bioimpedance measurement of a tidal volume (TV) of lungs and stroke volume (SV) and cardiac output (CO) sensors based on the measurement of the internal bioimpedance of the left ventricle have been lifted onto the shield. There is no single sensor giving adequate information for regulating the pacing rate. The carefully weighted resultant from multiple sensors can provide reliable information for setting the pacing rate. Artificial intelligence methods, the results of which are under strict supervisory inspection to avoid the possibility of fatal error, can be the direction for future developments [9–11].

#### **2.3 Principles of bioimpedance sensing**

For bioimpedance sensing, a low-level microamp (μA) range alternating current (AC) excitation of kilohertz range (kHz) is delivered from one electrode to another, and the caused voltage drop is measured. For example, these electrodes can be the pacing electrodes inside the right ventricle (in apex) and the case of implanted pacemaker [9]. Between these electrodes are situating both breathing lungs and contracting/relaxing myocardium of the beating heart [9–13]. As a result, we can measure the dynamic impedance of breathing lungs ZL(t) and of working myocardium ZM(t). The impedance ZL(t) gives the bases for calculating the tidal volume (TV), respiration rate (RR), and minute volume MV = TV × RR in liters. It is well known how the minute volume (MV) of breathing correlates with the physical work W of patient's organism, which, in turn, determines the need for a fresh oxygen-rich blood expressed through a stroke volume (SV) and cardiac output CO = SV × HR in liters. Heart rate (HR) is equal to pacing rate (PR) for pacemaker patients. Therefore, the pacing rate (PR) determines the amount of oxygen-rich blood (CO) directly. The described mechanism forms the pacing rate (PR) management principle in modern cardiac rhythm devices. However, because we do not know exactly the functional relationship between the required blood volume (CO) and PR, it becomes necessary to measure the effective CO and compare it with the desired comparison and negative feedback. With this, we achieve the automatic PR adjustment based on the feedback principle of closed-loop control [8, 14]. The feedback mechanism is provided determining the resulting stroke volume (SV) and cardiac output (CO) via measuring the electrical bioimpedance ZV of the right ventricle, which is inversely proportional to stroke volume [13].
