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Mechanical
Circulatory and
Respiratory Support
Editors
Shaun D. Gregory
Michael C. Stevens
John F. Fraser
ACADEMIC PRESS
An imprint of Elsevier
Contents
Contributors xxv
Preface xxxi
Acknowledgments xxxiii
PART 1 HEART FAILURE AND N0NDEV1CE TREATMENT
CHAPTER 1 Descent into Heart and Lung Failure 3
Introduction 3
Cardiac Anatomy and Physiology 3
Heart Chambers 4
Heart Valves and Coronary Arteries 5
Left Ventricular Mechanics 6
Cardiogenic Shock 8
Chronic Heart Failure 12
Respiratory Anatomy and Physiology 20
Structure and Function 20
Respiratory Pathophysiology 25
Conclusion 30
Acknowledgment 30
References 30
Further Reading 36
CHAPTER 2 Heart and Lung Transplantation 37
Introduction 37
History of Thoracic Transplantation 37
Decision-Making in Thoracic Transplantation 40
Recipient Evaluation, Indications, Contraindications for
Heart and Lung Transplantation 41
Indications for Heart, Lung, and Heart-Lung
Transplantation 42
Listing for Heart Transplantation 42
Listing for Lung Transplantation 42
Listing for Heart-Lung Transplantation 43
Contraindications to Heart and Lung Transplantation 43
Specific Contraindications To Heart Transplantation 44
Specific Contraindications to Lung Transplantation 44
V
Specific Listing Indications in Heart and Lung
Transplantation 44
Multiorgan Transplantation 45
The Heart and Lung Donor 45
The Effects of Brain Death on Donor Heart and LungFunction 45
Heart and Lung Donor Selection 47
Selection of Donor Hearts 47
Selection of Donor Lungs 48
Donor-Recipient Matching in Heart and Lung
Transplantation 49
Donor-Recipient Size Matching 49
Immunological Matching 49
Surgical Techniques 50
Donor Heart and Lung Procurement 50
Donor Procurement Operation 51
Immunosuppression 59
Immunosuppression Agents 60
T-Cell Directed Therapy 60
B-Cell Directed Therapy 61
Agents Targeting Cytokines 63
Pooled Polyclonal Antibodies as Immunosuppressive
Agents 63
Immunosuppressive Agents With Multiple Cellular
Targets 64
Cytotoxic Agents as Immunosuppressive Agents 65
Principles of Immunosuppression for Heart and Lung
Transplantation 65
Induction Therapy 65
Maintenance Immunosuppression 65
Treatment of Acute Rejection in Heart and Lung Recipients 66
Hyperacute Rejection 66
Acute Rejection 66
Chronic Lung Allograft Dysfunction 70
Malignancy 72
Airway Complications After Lung Transplantation 75
Cardiac Allograft Vasculopathy 77
Infection After Heart and Lung Transplantation 79
Other Complications After Lung Transplantation 82
Long-Term Complications After Heart and Lung
Transplantation 82
Contents
Survival After Heart and Lung Transplantation 83
Conclusion 84
References 84
Further Reading 89
PART 2 TYPES OF CARDIOVASCULAR DEVICES
CHAPTER 3 First-Generation Ventricular Assist Devices 93
Introduction 93
Principle of Operation 94
History of First-Generation VADs 95
Devices 98
Thoratec HeartMate 1 98
Thoratec PVAD 99
Thoratec IVAD 100
Abiomed BVS 5000 101
Abiomed AB5000 101
Arrow LionHeart 102
Berlin Heart EXCOR 103
MEDOS-HIA VAD 105
NIPRO-VAD 106
Novacor LVAS 106
ZEON VAD 107
Advantages and Disadvantages 108
Advantages 108
Disadvantages 109
Future Considerations 110
Conclusion 110
References Ill
Further Reading 115
CHAPTER 4 Second-Generation Ventricular Assist Devices 117
Introduction 117
Disadvantages of First-Generation VADs 118
What Defines a Second-Generation VAD? 118
History and Technological Approaches of
Second-Generation VADs 118
Different Approaches and Pump Types Within the
Second-Generation 118
Less Invasive VADs 119
Long-Term VADs 120
viii Contents
Extra- and Paracorporeal VADs 121
History: Timeline and Important Dates 121
Detailed Description of Major Second-Generation VADs 124
Available Devices 124
Devices Under Development 138
Discontinued Devices 138
Clinical Outcome and Comparison of First- and
Second-Generation VADs 143
Outlook for Second-Generation Devices 147
Conclusion 148
References 148
Further Reading 150
CHAPTER 5 Third-Generation Ventricular Assist Devices 151
Introduction 151
History and Status of Third-Generation VADs 153
Technology of Third-Generation VADs 155
Hydrodynamic Bearings 155
Magnetic Bearings 157
Profiles of Third-Generation VADs 159
Clinically Available Implantable Third-Generation
VADs 159
Clinically Available Extracorporeal Third-Generation
VADs 171
Third-Generation VADs in Development 173
Historical Third-Generation VADs 175
Summary and Future Considerations 179
Conclusion 181
References 182
Further Reading •186
CHAPTER 6 Biventricular Assist Devices 187
Introduction 187
Requirement for Biventricular Support 189
Device Requirements 190
Supporting Systemic and Pulmonary Circulations 192
Flow Balancing 194
Technical Considerations 195
Surgical Considerations.. 197
First-Generation Devices 198
Abiomed BVS5000 199
Contents ix
Abiomed AB5000 199
Thoratec PVAD 200
Thoratec IVAD 201
Berlin Heart EXCOR 202
Medos HIA-VAD 203
Second-Generation Devices 203
BioMedicus 204
RotaFlow 205
TandemHeart 205
Jarvik 2000 207
MERA HCF-MP23 207
ImpellaRP 208
Third-Generation Devices 209
Thoratec CentriMag 209
HeartWare HVAD 210
Summary and Future Considerations 211
Conclusion 213
References 214
CHAPTER 7 Total Artificial Hearts 221
Total Artificial Heart Requirements and Challenges 221
Origins of the TAH 222
Liotta-Cooley TAH (1969) 222
Akutsu III TAH (1981) 224
Jarvik 7 TAH (1982) 225
Totally Implantable TAH Technology 227
Sarns-3M TAH 228
Nimbus TAH 229
AbioCor TAH 231
The Future of TAH Technology 233
Rotary TAH 233
Positive Displacement 238
Conclusion 241
References 241
CHAPTER 8 Extracorporeal Membrane Oxygenation 245
Introduction 245
Circuit Configuration and Design 246
Primary Challenges in ECMO Circuit Design 246
Considerations for Circuit Selection 251
x Contents
Overview of Common Commercial Devices for
Extracorporeal Support 252
iLA Membrane Ventilator 252
CARDIOHELP System 254
HEMOLUNG RAS 254
Differences in Loading Conditions and Hemodynamics by
Configuration 254
Candidate Selection: Relative Indications and
Contraindications 256
Respiratory Support: Venovenous ECMO for
Hypoxemic and Hypercarbic Respiratory Failure 257
Extracorporeal Carbon Dioxide Removal 258
Cardiac Support 258
Extracorporeal Cardiopulmonary Resuscitation 258
Bridge-To-Transplant: Evidence for Awake ECMO
in Lung Transplantation 258
Use of ECMO in Primary Graft Dysfunction 259
Evidence in Heart Transplant 259
Additional Critical Illness Indications 259
Strategy for Management 260
Complications: Common Problems With Current Systems 261
Economics and Resources 261
Resource Utilization and Long-Term Outcomes 261
Center Volume 262
Future Prospects 262
Technological Developments 262
Ongoing and Future Clinical Trials 263
Establishing Care Standards Through Robust Research
Networks 263
Conclusion 264
References 264
CHAPTER 9 Pediatric Devices 271
Introduction 271
Etiologies of Heart Failure in Children 271
Cardiomyopathies 272
Congenital Heart Disease 272
Myocarditis 272
Patient Selection and Comorbidities 272
Contents xi
ECMO Devices and Short-Term VADs 273
The Pump 273
The PMP Oxygenators 274
The Cannula 275
Short-Term Pediatric VADs 279
Durable VADs 279
Pulsatile Flow VADs 281
Continuous Flow VADs 283
BiVADs and TAHs 284
Total Artificial Heart 285
Postoperative Management 288
Outpatient Management 289
Future Considerations 290
Destination Therapy 290
Pediatric Specific Devices 290
Conclusion 291
References 291
Further Reading 296
PART 3 PUMP DESIGN
CHAPTER 10 Hydraulic Design 301
Introduction 301
Classification and Performance of Blood Pumps 302
Geometry Design 303
Head and Power Estimation 303
Velocity Diagrams 304
Selecting Pump Type and Cordier Diagram 305
Viscous Effects in Designing Blood Pumps 309
Experimental Design 310
Test Rig Design 310
Hydraulic Performance Results 311
Hydraulic Losses in Rotary Pumps 313
Physical Description 313
Graphical Description 317
Properties of Pump Performance Curves 317
Computational Design 319
CFD Equations and Turbulence Modeling 321
Simulation Procedure and Result Validation 322
Numeric Pump Performance Estimation 325
Contents
Conclusion 331
References 332
Further Reading 334
CHAPTER 11 Motor Design and Impeller Suspension 335
Introduction 335
Motor Design 336
Considerations in Motor Design 336
Theory of Magnetism 338
Motor Topologies 344
Vector Control 353
Impeller Suspension 353
Mechanical Bearings 354
Hydrodynamic Bearings 354
Magnetic Bearings 355
Examples of Magnetic Suspension Systems for RBPs 367
Axial Suspension System With Double Stators 373
Conclusion 376
References 376
CHAPTER 12 Pulsatile vs. Continuous Flow 379
Introduction 379
Quantification of Pulsatility 381
Considerations of Pulsatile and Continuous Flow 383
Arterial Vascular Dysfunction 383
Blood Trauma 384
Gastrointestinal Bleeding 384
End-Organ Function 385
Specific Design Considerations 385
Left Ventricular Assist Devices 385
Total Artificial Hearts 389
Extracorporeal Membrane Oxygenation (ECMO) 394
Summary and Future Considerations 398
Conclusion 399
References 399
Further Reading 406
CHAPTER 13 Preclinical Evaluation 407
Introduction 407
In Silico Evaluation 408
Lumped Parameter (0D) Models 408
Contents xiii
Distributed (ID) Models 411
CFD/FSI (3D) Models 412
Multiscale Models 413
In Vitro Evaluation 414
The Windkessel Model 414
Resistance 415
Compliance 416
Inertia 417
Autoregulation 417
Mock-Circulation Loops 417
Particle Image Velocimetry 422
Ex Vivo Models 422
In Vitro Testing for Hemolysis 424
Standard for Evaluation of Hemolysis 425
Quantifying Hemolysis 425
In Vivo Evaluation 425
Model Selection 425
Acute Studies 427
Chronic Studies 428
Models of Heart Failure 429
Models of Acute Respiratory Distress Syndrome 430
Summary 432
Conclusion 433
References 433
Further Reading 438
PART 4 IMPLANTATION AND MEDICAL MANAGEMENT
CHAPTER 14 Optimizing the Patient and Timing of the
Introduction of Mechanical Circulatory and
Extracorporeal Respiratory Support 441
Introduction 441
Extracorporeal Respiratory Support for Respiratory
Failure 442
Acute Respiratory Failure 443
Chronic Respiratory Failure 448
ERS Summary 451
Mechanical Circulatory Support in Cardiac Failure 452
Acute Cardiac Failure 453
Chronic Cardiac Failure 459
xiv Contents
Advanced Extracorporeal Life Support in Cardiorespiratory
Failure 461
Conclusions 462
References.. 462
CHAPTER 15 Surgical Implantation 469
Introduction 469
Decision-Making 469
Technique 471
HeartMatell 471
HeartMate III 475
HeartWare HVAD 476
Total Artificial Heart Implantation 479
Extracorporeal Membrane Oxygenation (ECMO) 480
Other Left Ventricular Support Techniques 482
Management of the Right Ventricle 483
Protection of the Right Ventricle 483
Temporary Right Ventricular Support 484
HeartWare HVAD RVAD 485
Management of Valvular Pathology 487
Aortic Valve 487
Mitral Valve 488
Tricuspid Valve 489
Variations in Implantation 489
Alternate Outflow Cannulation Sites 489
Hostile Left Ventricular Apex 489
Minimally Invasive and Off-Pump Implantation 490
Conclusion 490
References 491
CHAPTER 16 Complications of Mechanical Circulatory and
Respiratory Support 495
Introduction 495
Part 1: ECMO-Related Complications 497
Introduction 497
Bleeding and Coagulopathy 498
Thrombosis 498
Other Hematological Complications 499
Cannulation Complications 500
Infection and Sepsis 503
Neurological Complications 503
Inadequate Support 504
Contents xv
Mechanical Failure 505
Specific Problems Related to Type of Support 505
Venovenous ECMO 505
Venoarterial ECMO 506
Patient-Related Complications 506
Pre-ECMO Severity of Illness 506
Timing and Natural History of the Disease 507
Etiology 507
Long-Term Complications of ECMO 507
Part 2: Complications in Durable VAD Support 508
Complication Rates in Pulsatile VADs 508
Bleeding 508
Thrombosis 513
Long-Term Complications 517
Conclusion 518
References 519
CHAPTER 17 Medical Management of the Supported Patient 529
Preparing for ECMO Support 529
Management of ECMO Flow 530
Access Limitation 530
Venoarterial ECMO Flow Management 530
Monitoring Distal Leg Perfusion 531
Venovenous ECMO Flow Management 531
Respiratory Management on Venovenous ECMO 531
Maintaining Adequate Oxygenation on Venovenous
ECMO 532
Management of Hypercapnia on Venovenous ECMO 532
Respiratory Management on Venoarterial ECMO 533
Differential Hypoxemia 533
Hypercapnia on Venoarterial ECMO 533
Anticoagulation 533
Balancing the Risks of Bleeding and Thrombosis 533
Heparin and Alternative Anticoagulants 534
Drug Therapies During ECMO Support 535
Sedation 535
Muscle Relaxation 535
Infections and Antibiotics 536
Investigations 536
Hemolysis: Detection and Management 537
Continuous Renal Replacement Therapy 537
Nutrition 538
Weaning Venoarterial ECMO 538
Weaning Venovenous ECMO 538
Decannulation: Venoarterial and Venovenous ECMO 538
Post Decannulation 539
Medical Management of Patients With Ventricular
Assist Devices and Total Artificial Hearts 539
Pre-VAD Assessment and Optimization 539
Assessment of RV Function 539
Fluid Status and Renal Function 540
Hepatic Function 541
Management of Bleeding Risk 541
Management of Infection 541
Nutrition 541
Anesthetic Considerations 541
Induction of Anesthesia 541
Monitoring 542
Use of Vasoactive Agents 542
Early Postoperative Management 543
Pump Settings 543
Hemodynamic Management 544
Mechanical Ventilation 547
Fluid Balance and Renal Management 548
Nutrition 548
Early Mobilization 548
Management of the Ambulatory Patient on Durable MCS 549
Setting the Pump Speed 549
Optimization of Pump Speeds 550
Exercise 552
Remodeling 552
Anticoagulation 552
In Intensive Care 552
Monitoring 553
Antiplatelet Therapy 553
Acquired von Willebrand Deficiency 553
Blood Pressure 554
Measurement Techniques 554
Outcomes 554
General Care 555
Driveline Management 555
Dressings 555
Contents xvii
Antibiotics 555
Antibiotic Prophylaxis Post Discharge 556
Exercise Therapy 556
Rehabilitation 556
Exercise Capacity 556
Activities of Daily Life 557
Conclusion 557
References 557
PART 5 PHYSIOLOGICAL INTERACTION BETWEEN
THE DEVICE AND PATIENT
CHAPTER 18 Cannula Design 567
Introduction 567
Thrombus Formation 568
Postoperative Bleeding 569
Perfusion 570
Ventricular Assist Devices 571
Inflow 571
Outflow 579
Total Artificial Heart 581
SynCardia Total Artificial Heart 581
AbioCor Total Artificial Heart 581
Alternative Total Artificial Heart Options 582
Extracorporeal Membrane Oxygenation 583
Cannula Design 584
Cannula Placement 588
Cannula Problems 589
Summary and Future Considerations 590
Conclusion 590
References 591
Further Reading 596
CHAPTER 19 Blood-Device Interaction 597
Introduction 597
Hemolytic Threshold of Blood 599
Effects of Hemolysis 601
Free Radical Generation Due to Hemolysis 601
Increased Free Hemoglobin Limits Nitric Oxide
Bioavailability 602
Contents
Changes in Blood Rheology 603
Effects of Mechanical Support on Blood Viscosity 603
Erythrocyte Functional Changes—Cellular
Deformability 605
Changes in Erythrocyte Aggregation 606
Effects of Altered Rheology 607
Changes in Platelet Function 607
Activation Due to Biomaterial Interface 608
Activation Due to Mechanical Forces 608
Coagulation Effects Due to Changes in Platelet
Function 610
Responses of Plasma Proteins 613
Fibrinogen 614
Von Willebrand Factor (VWF) 616
Albumin 617
Coagulation Cascade 618
Changes in White Cell Function 620
Potential Interventions to Limit Mechanical Damage 620
Conclusions 621
References 622
Further Reading 626
CHAPTER 20 Physiological Control 627
Introduction 627
Why Do We Need Physiological Control? 628
Native Heart Response to Circulatory Changes 628
Rotary Blood Pump Response to Circulatory Changes 628
Structure of a Physiological Control System 629
Control Theory Used in VADs 631
Rotary LVAD Control Strategies 632
Pressure Control 632
Flow Control 635
Multiobjective Control 639
Rotary BiVAD Control Systems 641
Summary of Physiological Control 642
Measurement and Estimation of Feedback Variables:
Closing the Feedback Loop 642
Direct Measurement: Sensors 642
Indirect Measurement: Estimation and Feature
Extraction 648
Contents xix
Future Outlook 649
Conclusion 650
References 650
CHAPTER 21 Percutaneous and Transcutaneous Connections 659
Introduction 659
ECMO-Associated Infections 659
Total Artificial Heart Related Infections 661
Ventricular Assist Device-Associated Infections 661
Clinical Significance of VAD-Associated Infections 662
Risk Factors of VAD-Associated Infections 662
Epidemiology of VAD-Associated Infections 662
The Emerging Link of Biofilms to the Pathogenesis of
VAD-Associated Infections 663
Biofilm Growth Initiates Percutaneous Driveline
Infections 663
Biofilm Growth Mode Plays an Important Role
in Persistence of Percutaneous Driveline Infections 666
Biofilm Dissemination and Migration Leads to Deeper
Tissue Infections 667
Preventive Strategies to Reduce VAD Driveline Infections 668
Patient Education and Care of Driveline Exit Site 668
Prophylactic Antimicrobial Agents and More
Advanced Surgical Techniques 668
Advances in Materials and Surface Engineering to
Combat Biofilm Formation and Driveline Infections 669
Transcutaneous Energy Transfer Topologies for
MCS Devices 674
Basics of Wireless Power Transfer 675
Performance Indices 676
Parameter Selection and Performance Optimization 676
TETS Coil Optimization 676
Power Converters 677
Repeaters for TETS 677
System Parameter Tuning 678
Control and Communication 678
Design Considerations and Practical Issues 678
Operating Frequency Selection 678
Backup Implantable Storage 679
Effects on the Body 679
Contents
Electromagnetic Exposure Limits 680
Summary and Future Directions 682
Conclusion 682
References 683
Further Reading 689
CHAPTER 22 Wearable Systems 691
Design of Wearable Peripherals: How They Developed
to the Current Status 691
Alarm Tracking and Pump Flow Monitoring 698
Battery Lifetime and Different Wearing Options 698
Technical Complications and Design Aspects of Wearable
Systems 699
Pump Cable and Connector Damage 699
Safety and Design Aspects of Power Supply and
Driveline to Controller Connection 702
Preclinical Design and Assessment: Human Factor
Engineering 707
Design of Clinical Trials and Best Practices for
Bench Testing 708
Usability Studies 708
Influence of Wearable VAD Peripherals on the
Quality of Life 712
Activity Restrictions 714
Physical Functioning and Quality of Life 716
Emotional Distress and Anxiety of Patients and
Their Caregivers 716
Outlook 717
Conclusion 718
References 718
Further Reading 721
PART 6 ROUTE TO MARKET (AND STAYING THERE!)
CHAPTER 23 Route to Market 725
Introduction 725
Where to Start? Founding the Company 727
Selecting the Proper Tax Structure for the Business 727
Forming a Board of Directors and the Executive
Management Team 728
Contents
The Business Plan/Executive Summary/Investor Slide
Deck 729
Business Plan 729
Executive Summary 730
Slide Deck 730
Creating a Valuation for the Company 730
Financials 731
Legal 731
Due Diligence 731
Intellectual Property 732
Insurance 732
Human Resources 732
Employee Benefits 733
Incentive Options and/or Shares in the Company 733
Managing Payroll 734
Creating the Device Development Plan 734
R&D Coordination With Quality Affairs 734
Create User-Requirement Specifications 736
Create a Product Specification 736
Begin Developing the Device 736
Perform a Risk Analysis and Failure Modes
Effect Analysis (FMEA) 737
Create and Execute a Preclinical Verification/Validation
(V&V) Test Plan 737
Regulatory Path 739
Clinical Trial Requirements 740
Orphan Designation 742
Good Laboratory Practice (GLP) 742
Good Manufacturing Practice (GMP) 742
Government Grants and/or Contracts 743
Sales and Marketing 743
Technical Support and Service 743
Crisis Management 744
Recalls 744
Warning Letters 745
Growing the Company Toward Profitability and
Sustainability 745
Exit Strategy—Liquidity for Your Investor 746
Conclusions 748
Acknowledgments 748
xxii Contents
CHAPTER 24 Cost-Effectiveness 749
Introduction 749
Cost-Effectiveness Analyses 749
Background and Objectives 750
Broader Context and Relevance for Health Policy
or Practice 750
Methods 751
Target Population and Subgroups 751
Setting and Location 751
Study Perspective 752
Comparators 752
Time Horizon 753
Health Outcomes 753
Estimating Resources and Costs 753
Choice of Model 755
Assumptions 758
Analytic Methods 759
Decision-Making 759
Results 760
Study Parameters 760
Incremental Costs and Outcomes 761
Characterizing Uncertainty 762
Discussion 763
Study Findings, Limitations, Generalizability,
and How It Relates to Current Knowledge 763
Conflicts of Interest and Source of Funding 767
Future knowledge 768
Conclusion 769
References 769
PART 7 SUMMARY
CHAPTER 25 The Past, Present, and Future 775
Introduction 775
How Technology Will Change Mechanical Circulatory
and Respiratory Support? 776
ECMO 776
Mechanical Circulatory Support 778
Emerging Applications for Mechanical Circulatory
and Respiratory Support 781
Contents xxiii
ECMO 781
Mechanical Circulatory Support 785
Organizing the Provision of Mechanical Circulatory
and Respiratory Support in the Future 788
ECMO 788
Mechanical Circulatory Support 789
Conclusion 791
References 791
Further Reading 798
Index 799
