Implantable pharmacological defibrillator with automatic recognition of ventricular fibrillation

The invention provides an automatic implantable defibrillator with the following essential characteristics: a) reliable recognition of a ventricular fibrillation state by noting mechanical ventricular systole noise and taking action if absent; b) effecting defibrillation not by electrical pulses fed to the heart but by a bolus of medicaments (or solutions under particular physical conditions, such as a cold bolus at 30.degree. C.) fed by a hydraulic system into the coronary sinus by a retrograde path to obtain an artificial circulation so as to rapidly pervade the coronary circuit. The symbol A.I.Ph.D. (Automatic Implantable Pharmacological Defibrillator) is proposed (D.A.I.F., Defibrillatore Automatico Impiantabile Farmacologico, in Italian).

In the known art, patients at risk from prolonged ventricular fibrillation 
crises are provided with automatic implantable defibrillators (symbol 
A.I.C.D.), generally composed of a cardiac rhythm alteration detection 
system able to determine ventricular fibrillation and usually designed to 
measure and interpret cardiac electrical signals, plus a generator which 
emits an electrical defibrillation pulse of the order of 20-25 J of 
energy. These instruments however currently suffer from numerous drawbacks 
which limit their use, and in addition are rather aggressive in their 
therapeutic action. These drawbacks include the following: 
as the electrical defibrillation threshold is not constant, the action may 
be ineffective; 
in the case of sustained ventricular tachycardia there is the risk of 
interpretation errors and hence of false positive indications with the 
probability of a worsening of the situation; 
possible non-recognition of fibrillation, with consequent lack of action; 
aggressive action in the case of application of epicardial patches, with a 
statistical mortality of 8-10%; 
considerable size and weight; 
possible myocardial lesion because of electric shock; 
early battery wear; 
considerable delay of action; 
reduced ventricular filling because of patches fixed to the ventricular 
wall. 
Thus, beside the technological availability, the A.I.C.D. is also very 
difficult to use. 
Most of these drawbacks are obviated by the type of instrument described 
hereinafter. 
Considering that the problems derive essentially from the difficulty of 
recognizing ventricular fibrillation and the impossibility of reliably 
defining the electrical defibrillator threshold, a system is proposed 
which differs in terms of these essential characteristics from those 
already available. 
As an alternative to electrical signal analysis, ventricular fibrillation 
can be recognized by determination of circulatory and pump arrest based on 
the absence of the mechanical sound produced by ventricular contractions. 
If circulatory arrest is determined there are two possible causes, namely 
asystole or ventricular fibrillation. 
The proposed apparatus then immediately produces ventricular stimulation by 
means of an incorporated pacemaker. If the cause is asystole the 
stimulation causes ventricular contraction, so restoring the alert state; 
the V V I stimulation proceeds if necessary, or stops if automatic rhythm 
is restored. If on the other hand the cause is ventricular fibrillation, 
the stimulation has no effect and after a few stimulations (2-4 or 
thereabouts) the instrument produces its defibrillation action. 
This is the second novelty of the proposed system. Instead of an electric 
shock a system of bolus-perfusion of antiarrhythmic and antifibrillation 
medicaments or cooled solutions is proposed. These are fed under a certain 
pressure directly into the coronary circulation via a catheter in a 
retrograde direction, inserted chronically into the coronary sinus or into 
a coronary artery.

On this basis the system, which is described in detail hereinafter, 
consists of: 
A) A subcutaneous generator implant contained in a casing of biocompatible 
metal (such as titanium) and comprising: the electrical power unit; the 
reservoir which can be refilled from the outside by a hypodermic needle; 
the propulsive system for the bolus infusion; the V V I or dual demand 
pacemaker; a telemetric programming system for choosing the pacemaker 
parameters (duration and amplitude of the stimulus, frequency, sensing 
etc.) and the bolus parameters (duration and possibly quantity). 
B) A venous-introduced catheter comprising: the stimulation electrode or 
electrodes; the noise detection sensor of piezoelectric or any other type. 
C) A venous-introduced catheter with an internal lumen, to be connected to 
the bolus emission system. 
As can be seen, in contrast to an AICD a thoracotomy is not required, but 
merely a simple implant similar to that for a normal pacemaker. 
With reference to FIG. 1, an example of a block circuit for obtaining the 
operating algorithm will now be described. An initial normal rhythm 
monitoring situation will be assumed. The catheter 1 is inserted venously 
into the patient in the manner of a normal pacemaker electrocatheter. The 
catheter 1 carries within its body the stimulation electrode 2 and the 
sensor 3 for sensing cardiac noise. This noise is caused by the movement 
of the cardiac muscle or by the blood flow during systolic pumping and 
corresponds to the initial phonocardiographic tone. Noise preceding the 
diastole is not sensed because of the refractory period described 
hereinafter. The electrical signal originating from the sensor 3 is 
amplified by 6 (A in FIG. 1B) to obtain an amplitude sufficient to control 
the circuit 7 (for example a monostable circuit) which generates a trigger 
pulse of constant characteristics (B in FIG. 1B). Via a monostable circuit 
8, this signal triggers a signal of programmable duration so as to blank 
the amplifier 6 in order to inhibit it for the time required for it not to 
sense signals due to diastolic cardiac noise. 
The signal B from 7 is also fed to the pacemaker 5 which uses it to inhibit 
its V V I operating generator, in parallel with the signal G sensed by the 
electrode catheter 2. The signal B from 7 also synchronizes a 
retriggerable monostable multivibrator 9, which is programmed for a signal 
of sufficient length to exceed the sum of 2 or 3 periods of the generator 
contained in the pacemaker 5. As 9 is retriggerable, the signals B from 7 
maintain its output Q at level 1, so impeding operation of the timer 
circuit 10 which is designed to start with a negative signal. The 
components 11 and 12 therefore remain at rest. 
The facility for telemetric programming can be provided in blocks 5, 6, 8 
and 10, to allow adjustment of the stimulation and defibrillation 
parameters after the implant. For example, it can be programmed the 
frequency and amplitude of the stimulus of the pacemaker 5, the sensing 
amplification 6, the refractory period 8 and the duration of the 
pharmacological bolus by 10; if the pacemaker is of dual demand type, the 
upper intervention frequency in the case of tachycardia will also be 
programmable. 
In programming the time of 10, an external program can be connected to make 
the time independent of the automatic circuit, so allowing continual 
perfusion from the outside or from the internal reservoir. 
It will now be assumed that a ventricular fibrillation episode begins. The 
cardiac noise becomes a murmur which is not sensed by the system 
comprising the sensor 3 and amplifier 4, so that the monostable circuit 7 
is no longer synchronized and no longer emits the signals B. After the set 
time the pacemaker 5, which is no longer inhibited by the signal B or by 
the signal G received from the electrode 2, commences stimulation via 2. 
As the cardiac muscle is in fibrillation the stimulus cannot be effective. 
Thus after the time programmed for 9, this multivibrator changes state 
from 1 to 0 to trigger the timer 10. This operates the propulsive system 
12 for infusion of the bolus of antifibrillation medicaments, this system 
being controlled by the actuator 11. An embodiment of this system is 
described hereinafter. The medicament bolus is injected into the coronary 
circuit by the tubular catheter 4, which is inserted into the coronary 
sinus or otherwise into a coronary artery. The duration of the signal F is 
adjusted on the basis of the quantity of medicament required to arrest 
fibrillation. 
When this happens, the stimuli emitted by the pacemaker 5 stimulate the 
heart if this is not able to restart spontaneously. In either case 
(stimulated heart or spontaneous rhythm) the normal monitoring conditions 
are restored, with the return of the cardiac noise signals B and the 
relative electrical signal G. 
If however the circulatory arrest is due to an AV block or an asystole, the 
pacemaker continues to stimulate until a spontaneous rhythm at higher 
frequency is restored. In this case the electrical pacing pulses continue 
in D and therefore E remains at high level, thus not allowing the bolus 
emission controlled by E, which is always at level 0. 
An embodiment of the infusion system for the pharmacological bolus will now 
be described. 
This system can be in the form of any mechanical and/or electrical system 
able to rapidly feed a sufficient quantity of medicament into the vein. It 
can consist for example of a rotary electric pump (peristaltic or not), a 
linear electromagnetic pump or an elastic mechanical system. By way of 
example, a hydropneumatic system has been chosen, which can result in a 
reduction in the size and weight of the implant as it requires little 
electrical power and allows the battery to be used almost exclusively by 
the monitoring and stimulation circuit, with the mere addition of a small 
solenoid valve. 
FIG. 2 shows one embodiment of such an apparatus. 
The arrangement of the various components of the bolus emission part shown 
in the figure can be actually used in practice, however the components can 
also be grouped and arranged in such a manner as to reduce the implant 
dimensions. In the figure the access port 16 for the necessary filling of 
the medicament reservoir 21 is shown separated from the reservoir 
structure. This arrangement can be used in practice as it makes the point 
for injection filling more easily recognizable from the outside. 
Alternatively, the port 21 could be located on the structure of the system 
13 in a position corresponding with the reservoir 21, in such a manner as 
to project from the structure of the implanted system and be easily 
locatable under the cutis. 
On this basis it can be seen that the described system comprises 
essentially the hydropneumatic system 13, the access port 16 for filling, 
and the solenoid valve 19 for emission of the bolus. The system 13 is 
composed of a capsule, which can consist, as in the figure, of two shells 
welded together in such a manner as to contain in their centre a flexible 
membrane 14 which in the figure is shown by way of example as a thin 
elastic plate of biocompatible metal (such as 316 stainless steel) made 
flexible by undulation pressing. It can however be of elastic plastics 
materials (latex, silicon rubber or the like). 
The chamber must be of sealed assembly. 
The part 22 of the system contains an inert gas compressed to a pressure 
sufficient to overcome the resistance of the external circuit to be fed 
with the pharmacological bolus. 
This gas is fed in through a tube 20 which is rigid with the chamber 22 and 
is hermetically sealed after filling. The chamber 21 is filled with the 
medicament to the extent of overcoming the pressure of the gas present in 
22 by displacing the flexible membrane towards the outer wall of 22. 
The following are connected to the chamber 21 either directly or via tubes: 
the access port 16 with a series-connected unidirectional non-return valve 
to prevent liquid flowing back to the port, and the solenoid valve 19 
(controlled by the circuit 11 of FIG. 1) which by its opening time 
determines the quantity of bolus injected. 
The door 16 is constructed on the standard basis, in the manner for example 
of access port for the injection of anesthetic liquids for analgesia, 
namely a resin piece bonded to a metal disc and a self-sealing rubber 
closure membrane to form a small prechamber 17 connected to the chamber 21 
via the tube and non-return valve 15. Filling is by a percutaneous needle 
through the rubber 18. 
The system constructed in this manner is simple and does not require 
electrical energy, and in addition is in practice rechargeable from the 
outside. The filling procedure also resets the position of the membrane 14 
such that the gas pressure is still active. Filling is by a system 
comprising a hypodermic needle, which perforates the port membrane 18 and 
is connected to a vessel containing the pharmacological liquid at a 
pressure slightly higher than that of the gas in the chamber 22, the 
system automatically halting delivery when the pressure reaches the value 
indicating maximum filling of 21. 
The reservoir 13 can be of a different shape than the circular 
cross-sectional shape shown in the example for simplicity of 
representation. The outlet of the solenoid valve 19 must be connected to 
the catheter to be inserted into the coronary sinus or otherwise into the 
coronary circulation. 
This catheter must have the following characteristics (see FIG. 3): 
a) Small dimensions to allow easy positioning; a diameter of between 1 and 
3 mm for the tube 23 can be acceptable. 
b) Its distal part should possibly, but not indispensably, comprise a 
system which prevents blood flowing back into the catheter, to prevent the 
formation of thrombi which could obstruct it, in which respect in addition 
to this mechanical system the antiarrhythmic pharmacological medicament 
can be mixed with heparin or the like. A non-limiting example of a 
possible arrangement is shown in FIG. 3, in which the tube 23 carries an 
endpiece which directs the liquid to the outside through the holes 25 and 
26. A thin elastic cap 27 (for example of latex or a similar material) is 
fitted by gluing at its proximal part onto the endpiece 24, the cap 
comprising in its distal part a hole which is made such that it is not 
normally in contact with the holes in the endpiece 24. When the 
pressurized liquid is emitted, its pressure moves the elastic cap forward 
so that the holes 26 and 28 communicate, to enable the liquid to emerge. 
When in its rest position blood is unable to enter. 
c) Immediately upstream of the distal exit of the catheter there can be 
provided, optionally for the purposes of the invention, a system which 
blocks the vessel into which the catheter is introduced so that the bolus 
liquid is unable to flow backwards into the vessel but is injected only 
into the coronary circulation. 
This could take the form of a portion of the catheter having in its wall 
holes 29 covered with an elastic sleeve 30 of such thickness that the 
pressure exerted by the injection system is sufficient to inflate this 
segment in the manner of a balloon. 
The entire described system can be contained in a single casing on which 
connections are provided for the stimulating electrocatheter and sensor 
and for the bolus infusion catheter. This however is not essential for the 
purposes of the invention, which can be constructed in the form of two or 
more units connected together. FIG. 4 shows how the two catheters can be 
inserted into the heart through the venous system, as in the case of a 
normal pacemaker implant.