Artificial Hearts
Partial Support
BiVAD doesnt cover the entire CI range LVAD supports fully left ventricle but doesnt support RV -capable of replacing CI = 2.5-4 LVAD supports partially left ventricle: ex - Impella does not support all of left ventricular function - about 1/3, not meant for long term function
TAH Anatomical fit Summary
TAH anatomy and interfacing with cardiovascular system: true TAH vs BiVAD connection with and without native atria
Asynchronous Pacemaker
generates pulse internally: 70-90 bpm pulses may be generated by a free running oscillator or microcontroller constant voltages (5.5V) or constant current (8-10 mA 1-1.2 ms) pulse are used lithium iodide batter - high source resistance
Asynchronous Pacemakers
generates pulses at a fixed frequency problems: excitation may occur too soon causing fibrillation or tachycardia natural and artificial pacemaker should not compete solution = frequency is higher than natural heart frequency
Pacemakers
asynchronous synchronous rate responding
typical viscosity
at 37 degrees is 1.2 N*s/m^2
continous flow
blood is propelled by spinning rotor patients do not have pulse
TAH
bridge to transplantation only FDA approved device: SynCardia
Demand pacemakers
generator is set to a certain frequency- typically 60-80 Hz after each pulse the generator resets itself and waits for certain periods of time to pass or for the QRS pulse if QRS is not detected, the the generator sends a pulse if QRS is detected, the generator is reset and the cycle begins again
Animal Studies
geometry of the device has to be altered to fit the animal model animal id monitored 24/7 blood analysis (every hour) looking for oxygenation, blood damage, kidney function etc blood pressure waveform is recorded (resting vs walking)
problems with animal studies
geometry/anatomy different blood properties calcification of membranes and valves thrombosis growth animals are healthy before implantation thus do not emulate the real clinical situation
Congestive heart failure
heart is unable to pump enough blood to deliver nutrients to the body around 6.5 million people live with CHF and 960,000 new cases annually projected to increase to 8 million by 2030
Axial Flow Pump - LVAD
heartmate II more common flow path comes straight through pump apex to aorta configuration
shear stress rate too high
hemolysis - red blood cells split
Advantages of TAH over BiVAD
higher survival rate patients undergoing long term support tended to have improved survival when supported under TAH - lower incidence of neurological events long length of mechanical support lower incidence of stroke or reoperation more successful in bridging patients to transplants
Blood Compatibility- physiological context
human body can remove around 20 g of free hemoglobin per day - 14g (12 mg/dL/hg) by renal clearance 6g (5 mg/dL/hg) by reticuloendothelial
Synchronous Pacemaker
ideally we should have intermittent cardiac pacing (for people who can establish normal rhythm between periods of block two types: demand pacemakers atrial synchronous pacemakers
Type of Errors
if the sample indicates that the mean is greater in the device treated group than in the controls (thus rejecting the null hypothesis) when in population there is no difference between means) a Type I error, also called alpha error, is made if the sample indicates no difference between means (accepting null hypothesis) when the device mean is actually greater, then Type II error is made
Advantages of TAH
immediately available at SynCardia centers patients recover rapidly up to 9.5 L/min through both ventricles 79% bridge to transplant eliminates complications cause by a failing heart patient's body automatically adjust blood flow reliability second to none hospital reimbursement
Freedom Portable Driver
investigational device, limited by US law to investigational use
heart disease
leading cause of death in the Us 1 in 7 deaths growing problem gobally
Anatomical fit
limited space in thoracic cavity limited availability to connect to exist vasculature
Tissue Compatibility
material mechanical anchoring contact pressure inside chamber: allow fibrous tissue, endothelial cell formation, binds to fibrous layer sometimes inner surface of the blood chamber is porous - HeartMate II outside: integrates with surrounding tissue, down not cause voltage bridges, inflammation, thermal burns
Full Support Requirements
max flow rate of 8-10 L/min max pressure 300 mmHg max ejection volume 70-80 mL
Body Surface Area
measures how well blood is flowing BSA= ((W*H)^1/2)/6 or BSA = ((W*H)/36)^1/2 W= kg H = m
LVAD Types
INCOR (intracorporeal)- inside human body EXCOR (extracorporeal)- outside human body
Non Invasive LVAD
Impela 2.5 non invasive axial pump LVAD
Mechanical Cadiovascular Orthotic Devices
Intra Aortic balloon Pump Left Ventricle Assist Device (LVAD) Bi-ventricular Assist Device Artificial heart
Cardiac Index
L/min/m^2 CI = CO/BSA or CI = SV*HR/BSA co= cardiac outpute L/min HR = heart rate bpm SV = stroke volume, L
LVAD Anatomical Fit Summary
Main types of devices: Axial Flow Centrifugal Pump LVAD anatomy and interfacing with cardiovascular system: atrium to aorta ventricular apex to aorta ventricular apex to abdominal aorta alternative connection to the left atrium and aorta Trend towards miniaturization of pumps for better anatomical fit
Right atrial pressure
0-7 mmHg pressure in atrium before flowing to ventricle
heart frequency
1-2 Hz
Maximal physiological stress
10 N/m^2 above 40 N/m^2 endothelial cells can be damaged
Pulmonary Arterial Pressure
15-39/8-14 mmHg
Cardiac Index
2.5-4 L/min/m^2
Mean flow of circulatory system
3-5 L/min
Left atrial pressure
4-12 mmHg
Normal shear stress
8-12 dynes/cm^2
Systemic Arterial Pressure
90-140/60-90
Cardiac Output
CO = MAP - MRAP/SVR or SV*HR MAP = mean arterial pressure MRAP = mean right atrial pressure SVR = systemic vascular resistance
Animal Models
Calves (TAH) - anatomical fitting, physiological testing Sheep(LVAD) - similar pulmonary vasculature Pigs (LVAD) - blood is closer match to humans Rats (LVAD)- ventricle loading and unloading LVAD procedure
Continous Flow LVADs
Centrifugal pump Does not have inflow tube Fits in chest cavity apex to aorta configuration
Clinical Trials
Control Groups: pharmacological therapy for CHF, do not receive the blood pump more common to have a new blood pump tested for efficacy and "non inferiority" another device in clinical trial a new blood pump is "non inferior" to an existing blood pump based on clinical data and patient outcomes For LVAD, the control device is heartmate II For TAH, the control device is Syncardia
In Vivo testing: Thrombus Formation
Danger of Stagnant Flow - thrombus formation
Newborn Oyxgenators
ECMO - Extracorporeal Membran Oxygenation
The Future of TAH
France CARMAT - sent to begin clinical trials in 2018 would rival the SynCardia
Humanitarian Device Exemption
HDE will allow up to 4,000 US patients annually who are not transplant eligible to receive the TAH on a permanent basis currently, these patients have no other options for long term survival and are often referred to hospice
Hemolysis Rate index
HRI =ΔHb*V*(100-Ht)/ T]
TAH Function Summary
Max flow rates Max pressure CI range Hydraulic Power
Normal Index of Hemolysis
NIH = = [ΔHb *V * (100- Ht)] / [(Q*T)/100] Hb = increase in free hemoglobin concentration (g/l) v = total blood volume (L) Q = flow rate (L/min) Ht = hematocrit in % T = duration of test
Null Hypothesis
No difference between untreated (control group) and treated group
Problem with Mechanical Support
No factor of safety for TAH microthrombo embolism hemolysis neurological problems infection pulmonary hypertensions acquired von Willebrand disease: deficieny of von Willebrand Factor - multimeric protein that is required for platelet adhesion result = bleeding
Power equation
P = flow * pressure
Pulmonary Vascular Resistance
PVR 2.8-3.9 mmHg/Lmin
LVAD- HeartMate II
Parts of LVAD: batteries controller pump must be placed on outside of body - easy to replace batteries, LI toxicity
Materials
Polyurethane- housing, membrane titanium - housing stainless steel - housing tygon medical/surgical - tubing Gore- tex
Right Side of heart
Pulmonary circulation
Stroke Volume
SV = EDV- ESV EDV = end diastolic volume ESV = end systolic volume
Systemic Vascular Resistance
SVR 24.6-29.8 mmHg/Lmin
Flow/ Pressure testing - Input Impedance
Zi = P/Q
Blood Pump Mechanical Power
around 1 W
Important Design Issues
anatomical fit physiological modelling blood compatibility tissue compatibility bench top testing Animal Testing Human Clinical Trials
Heartmate II LVAD
battery worn externally
Effects of Increased Hemoglobin
can cause endothelial cell dysfunction, vasomotor instability by reducing nitric oxide bioavailability, increased blood pressure, renal damage, and activation of platelets
Guaranteed treatment for end stage CHF
cardiac recovery is impossible limited supply of biological donor hearts lengthy wait time for donor heart
goals fo animal studies
device implantability an doperability show long term survival - more than 3 months demonstrate the blood pump's ability to sustain life and physiological function: animal survives in good health good arterial pressure, no pulmonary hypertension no indicators of bleeding or other complications good CO2 and O2, pH 7.38-7.41 Prove hemocompatibility: show low hemolysis show no thrombus formation inside blood pump and valves no thrombo-embolism in the brain, lungs Show adequate blood flow support (physiological CI) Show adequate perfusion (blood gases and post mortem)
Aortic Input Impedance for children vs adults
difference between age and vessel compliance with modulus of elasticity children's aortas are stretchier because they are still growing
pulsatile
either pneumatic or electromechanical flexible membrane or pusher plate with one way valves blood is sucked into chamber then expelled
TAH Physiological Responsive Desing
elastic membrane permits addition distension for changes in volume preload and after load as results of atrial pressures and changes to SVR and PVR
Types of Oxygenator Pumps
film type - large rotating disc in direct contact with 100% oxygen membrane oxygenator
Why resistance (SVR and PVR) is not enough to stimulate circulatory system
flow and pressure are not in phase with one another. each frequency the phase difference and amplitude ratios are different
LVAD function Summary
full support partial suport pulsatile vs non pulsatile
Physiological Function
full support (heart replacement, BiVAD, LVAD) partial support (LVAD) pulsatile or non pulsatile short term (days/weeks) long term (months) permanent
Pump Oxygenators
open heart surgery sometimes requires the heart is stopped O2 and CO2 exchange must occur elsewhere pump oxygenators provide mechanical pump and deliver oxygen to the blood stream as well as remove CO2 from vena cava to femoral artery right atrium to femoral artery femoral vein to femoral artery if oxygenator must be kept away from the heart
Pacemakers and Simulators
pacemaker: low current duty cycle stimulators defibrillators: high current single pulse mechanical cardiovascular orthotic devices
Pulsatile vs Non Pulsatile
partial pulsatile support needs to by synchronized with EKG usually synchronization assures that LVAD ejects blood when aortic valve is closed non pulsatile strategies can vary non pulsatile vs pulsatile debate: is pulsatile necessary? more prone to failure
Flow Studies
particle image velocity particle visualization surface washout - dye on surface stagnation area - dye in the volume valve flow - presence of jets, turbulence
Intra Aortic Balloon Pump
placed in descending aorta inflated during diastole when aortic valve opens, balloon is deflated deflation of the balloon decreases pressure seen by the heart, balloon generates region of lower pressure to which blood can easily be moved by weakened heart blood pressure waveform counter pulsation every other heart cycle the balloon is activated
electrodes
platinum alloys platinum with stainless steel, carbon, titanium elgiloy: cobalt chromium, iron, nicke, molybendum, manganese and traces of other metals
Pump Types
pulsatile continous flow pumps
TAH Anatomical Fit
pump inlets are mounted/integrated with left and right atria all heart valves and ventricles replaced outputs connect directly to the pulmonary artery and aorta via artificial valves pneumatic lines penetrate diaphragm
BiVAD Summary
pumps takes blood from left and right atrium ejects blood into aorta and pulmonary artery pulsatile VAD - blood pump stays outside of the human body
Wind Kessel Theory
rate of flow in aorta = rate of change of volume of elastic chamber + rate of flow into rigid tube windkessel theory describes flow pressure relationship in big arteries (aorta) only viable for large vessels, not the entire system
Atrium/ Inlet Variant 2
ventricles are removed as well as part of the atria and vessels ex: BiVAD - Berlin heart
Atrium/Inlet variant 1
remove ventricles and the valves leaving the pulmonary artery and aorta in tact Quick connects are sewn in and the TAH is replaces ex: SynCardia TAH
Problems with Human Studies
researcher bias patient bias control groups (ethical issues)- do not receive blood pump FDA allows TAH/LVAD experiments only with patients who are very sick - compassionate use
Types of Pumps
roller pump multiple finger pumps pulsatile pumps centrifugal pumps
Testing synthetic heart for blood compatibility
shear rate studies hemolysis- NIH, in vitro, in vivo thrombus formation - in vivo
Pre Market Studies ( Human Studies)
show safety and efficacy
Left side of heart
systemic circulation
shear stress rate too low
thrombus formation - blood clot hemolysis causes coagulation cascade which can cause clotting
Heartmate II thrombosis
thrombus formation was reported at the regions of the rear impeller hub and the entry of the impeller blades thrombus extended along the flow straightener blades
Purpose of blood circulation
transport and distribute oxygen and nutrients to tissue and remove by products
Types of BiVAD- berlin heart configurations
types: Left atrium to aorta configuration Left ventricle to aorta configuration installed outside the body for easy access to fix
Pharmacological therapy for CHF
use drugs to mitigate symptoms slows the onset
Numerical Modeling
use software to design and optimize the VAD/TAH prior to physical testing experiments speeds up the design process and reduces development costs prediction can be made regarding the overall pump performance - hydraulic performance, power usage some design question can only be answered through numerical modeling: fluid streamlines to predict flow path predictions of shear stress blood damage potential prediction of forces of the impeller or diaphragm predictions of thermal effects
Lead Wires
used to be most problematic part of device - 20% chance of failure in 10 years mechanically robust: helical coils, multiple stands well insulated: highly compliant silicone rubber or polyurethane as insulator unipolar: one electrode (negative) on the heart, second electrode away from heart bipolar: two electrodes within the heart placed against the inside surface of the heart
Controls blood flow in heart
valves
TAH surgical implantation
ventricles and valves are removed leaving pulmonary artery and aorta intact atria are preserved quick connects are sewn in and the TAH is attached
Post Market Studies (Human Studies)
with growing number of case studies safety can be better understood (rare cases of adverse effects will start showing up with larger n)