The Forgotten Driving Forces in Right Heart Failure: New Concept and Device*
Sayed Nour1,
Guifu Wu2,
Zheng Zhensheng2,
Juan C Chachques1,
Alain Carpentier1,
Didier Payen3
1 Laboratory of Biosurgical Research, Pompidou Hospital, University of Paris, France
2 Cardiovascular Research Center, The First Affiliated Hospital Sun Yat-sen University, Guangzhou, China
3 Department of Anesthesiology, Critical Care and SAMU, Lariboisiere Hospital, Paris, France
Sayed Nour, Tel: +0033140907615, Fax: +0033145405049, E-mail: nourmd{at}mac.com, Laboratory of Biosurgical Research, 96 rue Didot, 75014 Paris, France.
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ABSTRACT
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Background: Right heart failure is a frequent hemodynamic disturbance in pediatric cardiac patients. Besides inotropic and chronotropic drugs, fluid administration and inhaled nitric oxide, right ventricular mechanical assistance remains difficult to perform. A circulatory assist device adapted for the right heart biophysics and physiology might be more efficient. Materials and Methods: We are developing a prototype of a non-invasive cardiac assist device (CAD) for neonates and pediatrics. It is based on a pulsatile suit device covering and affecting all territories of the right heart circuit. It will be tested in a neonatal animal model of right ventricular (RV) failure. Experimental models will be matched and compared with control and sham groups. Expected results would be immediate hemodynamic improvement due to synchronized diastolic reduction of stagnant venous capacitance, increasing preload and contractility. On long term, increased shear stress with changing intrathoracic pressure in a phasic way would improve and remodel the pulmonary circulation. Future studies will be focused on: hemodynamic, biochemistry, endothelium function test, and angiogenesis. Comments: A non-invasive CAD guarantees better hemodynamics and endothelial function preservation with low morbidity and mortality. This is a physiological approach, cost-effective method, and particularly interesting in neonates and pediatrics with RV failure.
Key Words: Pulsatile suit • Right heart failure • Shear stress • Pediatric circulatory assist device
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INTRODUCTION
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Pressurized flow and shear rates are two constant endothelial stimulants that continue to regulate the closed hydraulic cardiovascular circuit since intrauterine life.1 Our heart and peristaltic arteries represent the main circulatory driving forces, otherwise accessory forces are necessary to move up the steady blood flow at the right heart side.2
Surprisingly the right heart could adjust blood volume and shear rates at 5 different anatomical zones according to its physiological demands. In antenatal period, the right heart receives and pumps in equal rates more volume than the left, but keeps low remodeling due to pressure release through physiological shunts.3 After birth and shunts closure, both right and left ventricles share equal volume and rate inducing equal pulmonary and systemic cardiac output (CO), but remodeling remains inferior at the right heart side most probably due to venous steady flow and ventricular wall trabeculae.
According to Guyton concept,4,5 the venous side blood volume can be considered containing two volumes; first the "unstressed volume" that fills the venous circuit without generation of driving flow forces; second, the stress volume that is mobilizing blood towards the right ventricle. Change in partition between these 2 components is physiologically obtained by sympathetic overflow or by fluid loading.6 The consequence of this partition modification is a change in right heart filling and performance. According to the net effect, this may improve physical performance in healthy persons or cardiac congestion with nitrates in cardiac failure. Although professional scuba divers and astronauts are subjected to totally opposite superficial surrounding pressures, they share almost the same circulatory disorders.7,8 This may result from a trend to reduce the driving pressure for venous blood, since forward and backward pressures tend to equalize.9
In general right ventricular (RV) hemodynamic disorders could be improved by intravenous fluids and chronotropic and inotropic drugs with or without pacemaker.10 This improvement has potential negative impact such as right side congestion (liver and kidney congestion) and/or reduced right ventricle coronary perfusion during pacing.
Conversely to adult context, right heart failure occurs more frequently in pediatric patients with more endothelium dysfunction than atherosclerosis.11 As a consequence, left heart cardiac assist devices as intra-aortic balloon pump cannot be efficient because of the large vessel compliance in pediatric patients.
The aim of this work is to develop a non-invasive cardiac assist device (CAD) to improve or replace accessory driving forces, adjust the requested volume and rates in each zone of the right heart circuit in regular synchronized pulsations. Leading to a better hemodynamic as well as remodeling specially in the very young populations.
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CONCEPT AND DEVICE
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Understanding volume and rate interdependency mechanism is the main concept of this study for building up the best device adapted to the right heart physiology and biophysics. As shown in (Table 1
) and (Figure 1) we could distinguish 5 different anatomical zones:
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Figure 1. Represents the 5 different remodeling zones of the right heart circuit as following: • Zone 1 (Z1) represents the superior vena cava (SVC) and inferior vena cava (IVC) low remodeling zone. • Zone 2 (Z2) represents a mild remodeling zone of the right atrio-ventricular cavity (A-V cavity). • Zone 3 (Z3) represents a normal remodeling interventricular septum zone. • Zone 4 (Z4) represents high remodeling infundibular zone. • Zone 5 (Z5) represents a pulmonary artery low remodeling zone.
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Zone1: low remodeling systemic venous zone, where blood is driven from extremities helped by the aforementioned accessory driving forces in a low pressure, steady stream flow.
Zone 2: mild remodeling atrio-ventricular cavity zone, where the tangential frictions wall stress is induced by contractions are tamed and alleviated by trabeculae in order to keep the right ventricular mass almost the 1/6th of the left one.12
Zone 3: normal remodeling zone, represented by the interventricular septum.13
Zone 4: high remodeling infudibular zone.
Zone 5: low remodeling zone of the pulmonary arterial tributaries, with low resistance and pressure as shear forces are already alleviated due to trabeculae, rotation and squeezing axis of the RV, infudibulum, the pulmonary artery compliance capacity, competent valves and less developed Valsalva.
Device design:
A 3 layers, pulsatile suit composed of detachable parts: a. trouser, b. waist belt, c. chest jacket. The three parts will be reassembled together in one unit and wrapped tightly around the patient body through straps and zippers, as shown in (Figure 2) and as patent descriptions (WO/2008/000111).
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Figure 2. Shows 4 schematic figures (A,B,C and D) of the pulsatile suit cardiac assist device (CAD): • (A), represents a whole figure of the pulsatile suit in 3 units compartments (jacket, belt and trouser), reassembled together and detailed as following: 1 = Zipper and straps, are conceived to keep the suit tightly fit to the body. 2 = Holes, to allow body access for medical management. 3 = Security air release valve, to avoid over inflation accidents in case of mechanical failure. 4 = Airport connectors, adapted to pneumatic rhythmic driving force. 5 = Inner layer in direct contact with the skin, made of elastic material (e.g. neoprene). 6 = Sandwiched, middle layer, contains gelatinous fluid, allowing mitigation of pulsed shocks, and facilitating impulses propagation. 7 = Air receiving external space, connected directly to pneumatic driving force, through airports (4), and security valves (3), to allow air delivery inward-towards the body in safe manner. 8 = Non-inflatable parts at the posterior parts of the suit to avoid spinal injury. • (B) = Represents the supra-diaphragmatic compartment of the suit, means a Jacket, composed of vest and 2 sleeves, that could be reassembled together through zippers and straps to fit the patient body tightly and securely to be used as circulatory as well as respiratory assist. • (C) = Trouser and waist Belt, representing the infra-diaphragmatic compartment of the suit. • (D) = Shows the 3 suit layers: (5–7) arranged inward-outward respectively, with air release security valve3 attached to the external layer7.
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The suit would be connected to a generator of rhythmic driving force, through specific connectors. Regular pulsations would be obtained via a currently used pneumatic driving forces, or a specific either pneumatic or low voltage-electric system.
The suit must be suitable for the postoperative situations and provided with security features as following:
- Inner layer made of elastic material (e.g. neoprene) to insure smooth tight massage like pulsed surge at the baby’s delicate skin.
- Middle sandwiched layer filled with gelatinous fluid, to alleviate the vigorous inflation/deflation, power induced by the driving force.
- External layer made from tougher materials to keep the pulsed wave inwards toward the body. This part is equipped by security air releasing valve to prevent over inflation accident in case of mechanic defect.
- Holes are previewed in the suit body, in order to facilitate medical administrations and prevent bedsores.
- Layers thickness and design are modified according to age, body weight and indication of the patient.
- The back portion of the trunk part of the suit (vest and belt) must not be inflatable in order to avoid any spinal, or back injuries.
- Blood must be pulsed back from periphery towards the heart in a sloping progressive wave in longitudinal axis. Except at the chest part, pulsations must be started backward - forward towards the front, in a horizontal axis in such a manner to increase venous return within respect of the respiratory movement.
- Device manipulation including pulse rate, inflation volume . . . etc must be adapted to each clinical situations to insure a harmonic, homogenous venous return waveform, in continuity with each part.
- The chest jacket and sleeves must be synchronized together in a manner to avoid respiratory distress or vascular incidents at the armpit, e.g. thrombosis, edema.
- Each suit component has its own inflation/deflation control security valve. This allows different pressure application according to different parts of the delicate pediatric body.
Models: a neonatal animal model of right ventricular (RV) failure. Future studies will be focused on: hemodynamic, biochemistry, endothelium function test, and angiogenesis. Experimental models will be matched and compared with control and sham groups.
Patients: The suit could be applied in clinical trials, in patients with chronic RV failure after right heart bypass operations as secured non-invasive device.
Expected results: would be immediate hemodynamic improvement due to synchronized diastolic reduction of stagnant venous capacitance, increasing RV preload and contractility. On long term increased shear stress with changing intrathoracic pressure in a phasic way would improve and remodel the pulmonary circulation.
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DISCUSSION
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The pulsatile suit could assist or replace some of the troubled accessory driving forces and factors (Table 2), that affect the right heart circuit.14 A tight elastic suit driven by regular external synchronized pulsations could induce a continuous harmonic compressive waveform movement over the body. This blood movement is obtained by squeezing stagnant venous capacitance which is usually accumulated at the superficial venous - lymphatic vessels and visceral area in infants. The consequence for right heart would be a better filling inducing a better function to push blood towards pulmonary circulation. In addition, this principle could increase vascular shear stress in pulmonary circulation which has been described as an important controller of the downstream vascular resistances.15
The potential effect of the device on the different defined anatomical zones can be viewed as follows (Table 3): Increased volume in zone "1" induces venous circuit hemodynamic disorders with a venous congestion, reduction of such a congestion is a major goal for treatment. To achieve it, one can use diuretics, increase in venous capacitance by nitrates and improve in right ventricular pumping by inotropic-chronotropic drugs.
This strategy may have side effects such as a non adapted reduction of preload, increase myocardial oxygen consumption related to tachycardia, and arterial blood pressure fall.
The proposed device would improve the mobilization of the venous congestive blood towards the pulmonary circulation synchronized or not with the right heart rhythm, in a more physiological way. It keeps the optimal preload, does not increase the heart rate, and reduced the venous congestion.
In addition, for the zone 2 and 3 for which the diastole is essential, the device may help to oxygenate the trabeculated crypts and the ventricular septum coronary circulation particularly in complex congenital heart disease.20 In zone 4 and 5, both volume and rate are needed to keep pulmonary resistance as low as possible in acute situation. A sustained better volume put the pulmonary circulation in a condition of remodeling. If such a remodeling is over efficient in absence of endothelial function, it might induce pulmonary vascular hypertrophy leading at maximum to an Eisenmenger syndrome.16 The proposed device might overcome such inconvenience by decreasing pulmonary afterload through endogenous nitric oxide process and enhancement of ventricular mass remodeling, particularly in patients of sub-acute and chronic pulmonary hypertension.
The previous systems used for management circulatory disorders such as anti-G suit17 cannot be used in pediatric context. Cardiomyoplasty as bioassist device,18 which was used in RV failure by increasing shearing rate only in volume dependent zone 2 and 3, might not be efficient for right heart bypassed patients. The other devices (Table 4), such as enhanced external counter-pulsation (EECP)19 are mostly indicated and usable for adults and do not fit well with pediatric patients. They induce strong and vigorous compression forces on deep arteries and on thoracic cage, which may have side effects in the pediatric patients.
Concerning clinical application of this concept and device, it is important to remark that this is the first described "non-invasive cardiac assist device" for neonates and pediatrics. It will be equipped with security features facilitating clinical use, e.g.: in cases of failed Fontan procedure with no issues except heart transplant.
It is important to consider the right heart compliance in physiological conditions (represented by Z1 in our concept). Since the right heart circuit contains almost 64% of blood volume, i.e. venous compliance is 10–20 times greater than systemic arterial compliance, therefore the right heart represents a compliant chamber and a good candidate for positive remodeling.21 A decreased pulmonary vascular resistance is the mean target in any case of right heart hemodynamic disturbances, which is shear stress-mediated endothelial nitric oxide synthesis (NOS) dependent. Clinically in acute RV failure, the improvement of hemodynamics with chronotropic drugs or pacemaker is directly related to increased pulmonary shear rates. Except our proposed pulsate suit, nothing is currently available for the chronic phase of RV failure management.
Proven clinical evidences show that the RV is a preload dependent ventricle, necessitating both systolic and diastolic phases for its oxygenation. RV is seriously jeopardized in cases of decreased venous return, for this reason is highly recommended to avoid nitrates in RV ischemia. Recently it was shown improved Norwood’s operation results with the Sano’s shunt, due to increased RV diastolic filling. Maintained RV volume by IV fluids is mandatory in cases of RV failure. Otherwise it is true that vigorous abrupt squeezing forces could deteriorate the overloaded RV, for this reason the device is equipped with security features, as been detailed, to insure sloping smooth regularly synchronized pulsed waves at the level of the superficial venous system.
We believe that this concept is a cornerstone approach in RH failure management. Currently we are testing prototypes in neonate piglet’s models with acute pulmonary hypertension (Z5) and acute RV failure (Z2). Future studies will include application of this concept in chronic or sub-acute phase of right heart failure models, which are usually affecting (Z1).
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CONCLUSION
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A pulsatile suit is a physiological, non invasive therapeutic method to manipulate the right heart side natural blood reservoir containing almost 64% the total blood volume and endothelium stores. Such a reservoir serves as a physiological therapeutic backup in case of hemodynamic disturbances and circulatory disorders particularly in pediatrics.
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ACKNOWLEDGMENTS
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We would like to express our gratitude to the following Doctors: Claude Planche, MD, Yves Lecarpentier, MD, Guy Mazmmanian, MD, Pierre Chastanier, MD, Daniel Carbognani, MD, Gerard Dine, MD, from Paris (France), and Marc Deleval, MD from London (UK).
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Footnotes
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* This paper was presented at the 4th International Cardiac Bio-Assist Association Congress, 12–13 March 2008, Singapore. 
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Asian Cardiovasc Thorac Ann 2009;
17:525-530
© 2009 by SAGE Publications
DOI: 10.1177/0218492309348638
TOP
ABSTRACT
INTRODUCTION
