For patients with normal A-V conduction system, AAI mode pacemaker is sufficient for bradycardia therapy. However, for patients with an abnormal A-V conduction
system, dual chamber pacemakers are needed to maintain A-V synchrony and heart rate. In the figure below we simulated a patient with bradycardia and concealed type II
(Wenckebach type) heart block. The mechanism of this kind of heart block was shown in Medical validation of VHM. The heart model on its own appears to have simple bradycardia
with 1:1 atrium to ventricle conduction. A physician may prescribe a simple single-chamber AAI pacemaker, which can only pace and sense in the atrium. However, by
running the AAI pacemaker and the heart model together, it becomes obvious that this mode is not adequate for this situation. The pacing interval of AAI
pacemaker is short enough to activate on RRP of the AV node, thus lengthening the ERP interval and causing AV nodal conduction delay. We can see a gradually
prolonged A-V delay until there is a dropped beat at (1) in the ventricle. The AAI pacemaker cannot sense this dropped beat, nor can it pace the ventricle in order
to prevent the dropped beat. Using the real-time models, we can show that this situation requires a more sophisticated dual-chamber pacemaker. A DDD mode
pacemaker can maintain proper pacing in this complicated arrhythmia situation, as shown in the figure below. The pacemaker model delivers pacing to both the atria and the ventricles at a proper rate to maintain AV synchrony and hemodynamics.

While simple pacemaker operations can be satisfactorily verified using pre-recorded electrogram signals, the high-level operations require a complex and interactive platform for validation and verification. The VHM provides this interactive device-in-the-loop environment, where pacing therapy from the pacemaker software will directly cause changes in the VHM, creating a more realistic testing environment. This also allows the testing parameters to cover a greater span of arrhythmias. With the VHM, we can create multiple arrhythmias to test the interactions between different features of the pacemaker.

Cavotricuspid-Isthmus-Dependent (CTI) Atrial Flutter (AFL) is a commonly seen supraventricular arrhythmia. The physiology of the right atrium, shown in the right panel the figure above, lends itself to forming conduction pathways along pathological tracks. Slow conduction through the CTI, the area bounded by the inferior vena cava and the tricuspid valve annulus, creates a long cycle length in the tissue and allows for the reentry circuit to form. Typical AFL occurs in the counter-clockwise direction, with activation following the posterior atrial wall through the CTI, along the inter-atrial septum, back across the anterior wall, and down the exterior wall. Clockwise direction conduction, known as reverse AFL, is also seen but is not as common. AFL encompasses a large portion of the atrium in a reentry circuit with rates up to 350 beats per minute. It is associated with significantly high morbidity rates because it occurs in transition from a regular rhythm to atrial fibrillation.

The reentry circuit for AFL is modeled in the VHM by placing additional nodes and paths in the right atrium connected to the SA node. In order to model the reentry circuit with cycle length 226 msec, the sum of conduction timers for all paths along the circuit equals the cycle length. The effective refractory timers for the nodes in the circuit were set to 150 msec, which allows the condution to continue through the nodes without encountering block. However, the effective refractory timer for the AV node is known to be 500 msec. This means that every other activation signal conducted through the atria will be blocked at the AV node and not conduct to the nodes and paths in the ventricles, causing 2:1 conduction. The underlying bradycardia is modeled by setting the rest timer of the SA node to be 1000 msec. Simulated synthetic EGMs are shown below:

The AFL rate of 240 to 350 bpm dominates the intrinsic slow rate of the SA node, and causes activation to conduct to both atria. Commonly, this rapid activation in the atria causes the conduction properties of the tissue downstream towards the ventricles to slow. This blocks several activations from conducting to the ventricles and results in a 2:1 atrium to ventricle conduction ratio . The atrial rate is very fast while the ventricular rate remains relatively normal, around 100 beats per minute. When the AFL terminates on its own, the diseased heart returns to a bradycardia state.

In many cases, patients require a dual chamber pacemaker to maintain synchrony between atria and ventricles, such as in bradycardia with heart block. The Post Ventricular Atrial Refractory Period (PVARP) is a period after each ventricle event that no atrial event should happen. In DDD mode pacemaker, atrial events sensed during PVARP will be marked as AR and will not trigger ventricular pacing\cite{Jiang1}. The figure below illustrates the situation where a DDD pacemaker can cause more harm than good. Although some atrial events fall into the PVARP period of the pacemaker and are ignored (AR in the figure), the ventricles are still paced for every sensed atrial event (AS in the figure), which results in rapid and irregular pacing of the ventricles with rates up to 150 beats per minutes, creating a ventricular tachycardia. At rates this fast, the ventricles do not have enough time to fill between contractions, and pumping efficiency suffers.

For patients who require dual chamber pacing due to bradycardia and have intermittent supraventricular tachycardias, a more advanced mode of pacemaker operation is necessary. The mode switch operation can disable the atrial pacing function of a DDD mode pacemaker and turn it into a VDI mode pacemaker during supraventricular tachycardias while switching back to DDD mode when the AFL terminates. The figure below illustrates how a mode-switch would occur in closed-loop operation with the VHM. The pacemaker starts in DDD mode. The pacemaker constantly monitors the atrial beat-to-beat interval and records the number of intervals shorter than 500ms. When there are five consecutive short intervals in the atrial channel (both AR and AS), mode-switch occurs from DDD to VDI mode. In VDI mode, the pacemaker decouples atrial sensing and ventricular pacing. The ventricles are paced at the LRI of 800ms and only when a ventricular event has not been sensed.

Most supraventricular tachycardias are transient and eventually terminate on their own. The pacemaker must be able to mode-switch out of VDI mode to regain its normal operation when the tachycardia terminates. The pacemaker continues to monitor the atrial rate in order to detect when the AFL terminates, characterized by an interval recorded to be longer than 500ms. This triggers the reverse mode switch from VDI to DDD. If the interval length exceeds the LRI interval, the pacemaker will switch to DDD mode and simultaneously deliver an atrial pace to maintain natural conduction pattern.

Oversensing is a general term for inappropriate sensing caused by noise or far-field signals. It’s very common among pacemaker malfunctions and it may trigger adverse effect or inappropriate therapy. Generally it can be treated by adjusting the sensitivity of the sensing circuit or the blanking and refractory period in pacemaker settings. But in some special case like ICD, these adjustments may result in missed events.

Crosstalk is a special case for oversensing which occurs when the pacemaker stimulus in one chamber is sensed in the other chamber. It happens when two leads are close to each other or pacing signal in the other chamber is too strong. Other than adjusting appropriate thresholds for the sensing circuit, there are several means to prevent crosstalk or avoid its consequences. First, a short blanking period during which the sensing circuit in one channel is disabled after pacing in the other channel. Second, a Ventricular Safety pacing mechanism is introduced to prevent the inappropriate ventricular inhibition.

In this case we’ll show how oversensing caused by crosstalk can trigger inappropriate pacemaker mode switch. We use VHM to simulate a patient with intrinsic rate:100bpm and prolonged AV conduction. A DDD pacemaker is implanted in order to maintain A-V synchrony. The Atrial lead is placed in the right atrium and the ventricle lead is placed in the right ventricle outflow tract rather than the right ventricle apex.

Since the ventricle lead is placed close to the right atrium, the atrial lead can sense far-field ventricular signal during Ventricular pacing(marker 1 in the figure on the left. If the sensing threshold of the atrial channel is low, the far-field signal can be treated as atrial event by the pacemaker. Since the signal is shortly after Ventricular pacing, it falls into the PVARP period thus won’t trigger atrial sense and is marked as [AR](marker 2 in the figure on the left). The interval between two intrinsic atrial events(AS) is 600ms and is longer than the SVT sensing threshold of 500ms. However the sensed far-field signal(ARs) doubled atrial events and the atrial rate sensed by the pacemaker exceeds the SVT sensing threshold. The mode-switch function of the pacemaker is triggered and the mode switched from DDD to VDI(first MS marker in the figure on the left). During VDI, A-V synchrony is not maintained, which leads to inappropriate therapy since A-V synchrony should be the primary treatment for this particular patient. During the same period an intrinsic ventricular event happened(marker 3 in the figure on the left). Since the amplitude of an intrinsic ventricular event is not as large as a ventricular pacing signal, no far-field sensing happened in the atrial channel and the rate sensed by the pacemaker dropped below the SVT threshold. The pacemaker then switches its mode from VDI to DDD to maintain A-V synchrony(2nd MS marker in the figure on the left). In this case mode-switch happens for every 3 intrinsic atrial event and switch back after one intrinsic ventricular event. The frequent mode-switch may potentially drain the battery of the pacemaker faster.

In order to avoid this behavior, we can simply lower the sensing threshold in the atrial channel to avoid oversensing. In the figure on the right we lower the sensing threshold and the far-field signal is not treated as atrial event. The pacemaker can thus provide effective atrial tracking and save battery.

Lead displacement affects many patients and can lead to inappropriate or ineffective therapy. In this cases, We use VHM to simulate a patient with bradycardia(intrinsic rate:50bpm) and delayed AV conduction. A DDD pacemaker is implanted to maintain heart rate and A-V synchrony.

The figure below shows the simulation result for the pacemaker function when the leads are in their designated location. From the figure we can observe: 1) Each P-wave is initialized by an Atrial Pace signal. 2) Each QRS complex is initiated by a ventricular pacing signal. 3) The interval between AP and VP is 150ms, which matches the programed AVI period.

For some reason, the atrial lead dislodged and fell into the right ventricle outflow tract, as shown in the figure below. As the result the atrial lead will sense ventricular signal rather than atrial signal and will initiate ventricular event when it paces. The figure on the above right shows the simulation results after the atrial lead dislodged. The figure reveals several facts: 1)No P wave is sensed or tracked. 2)Atrial Pace initiates a abnormal, wide QRS which is then sensed by the ventricle lead. 3)intermittent appearance of VP on QRS 110ms after the AP.

The ‘Double pacing’ in the ventricle is caused by Ventricular Safety Pacing which is triggered by a ‘Racing condition’(The figure on the right). There are two sources for stimuli: the intrinsic pacemaker SA node and the atrial lead. Stimuli originated from SA node will arrive the ventricular lead through a fast pathway(SA-AV-His) and stimuli originated from the atrial lead will arrive the ventricular lead through a slow pathway formed by ventricle myocardial. The ‘Atrial Pace’ will inititiate a ventricular event which will be sensed by the ventricular lead. With normal AV conduction, this signal will arrive the ventricle lead after the Atrial Blanking Period and Crosstalk Sensing Window which follows the ‘Atrial Pace’. In this case, the ventricle is paced by the atrial lead every LRI period and the pacemaker is actually functioning like in VVI mode. However, since the intrinsic P waves are not sensed and traced, An intrinsic P wave may happen slightly before the ‘Atrial pace’ and sensed by the ventricular lead before the paced signal arrives. In this case the intrinsic ventricle activation conflict with the paced ventricle activation, causing uncoordinated ventricle contraction which may affect cardiac output. If the intrinsic signal is sensed during the crosstalk sensing window, Ventricle Safety Pacing is triggered to pace the ventricle 110ms after the AP. Although the pacing is ‘safe’ because the pacing is early enough to avoid vulnerable refractory period, the damage caused by pacing on depolarized tissue is unknown.

Pacemaker Mediated Tachycardia (PMT) is the circumstance where the pacemaker paces the heart at an inappropriately high rate. In the following two cases, we observe the pacemaker can introduce complications that may lead to unsafe heart conditions.

Endless Loop Tachycardia (ELT) is a situation where the pacemaker and heart tissue form a “circuit”, which is known as reentry circuit. Reentry circuit is one of the most common reason for Tachy-arrhythmia. Its mechanism is based on timing anomalies caused by additional (accessory) conduction pathways within the heart. In this situation the “additional pathway” is the pacemaker AV synchrony function. The figure on the left shows the mechanism of ELT where natural conduction pathway serves as the slow pathway of the circuit and the A-V synchrony function of the pacemaker serves as the fast “pathway”. A Premature Ventricle Contraction (PVC) can trigger retrograde conduction through the slow pathway and triggers atrial sense event in the pacemaker. The pacemaker will then pace the ventricle after the AVI timer runs out, triggering another retrograde conduction and causing reentrant tachycardia. The VHM’s simulation result is shown in the figure on the right. The first ventricle sense (VS) is a Premature Ventricular Contraction (PVC). It propagates retrogradely to the atrium and triggers atrial sense (AS). The AS-VP interval is equal to the AVI timer value of the pacemaker. The VP-AS intervals are equal to the first VS-AS interval, indicating all VPs are also going retrogradely to the atrium. The resulting heart rate is around 150bpm.