the RIGHT HEART.

Foreword
Preface
Contents
Part I: Physiology, Pathology and Pathobiology
	1: Function of the Right Ventricle
		From Early to Recent Ideas on RV Function
		Physiology of RV Contraction and Relaxation
			Myocyte Contraction
			Myocyte Relaxation
		RV Contraction, Ejection, and RV Pressure Curve
		Influence of LV Contraction on RV Ejection
		Description of RV Function
		The Ventricular Pressure-Volume Loop
		Systolic Properties: The End-Systolic Pressure-Volume Relation
		Considerations for the Application of RV ESPVR and Ees
		The Cardiopulmonary System
		Diastolic Properties: The End-Diastolic Pressure-Volume Relation
		Single-Beat Analysis of Ees and Eed
		Regulation of RV Function
		Volume Response: The Frank-Starling Mechanism
		Afterload Response: Sympathetic Activation
		Conclusions
		References
	2: Right Ventricular Pathobiology
		Introduction
			RV Functional Decline and Recovery Are Highly Variable
			RV Failure Is in Part Independent of Pulmonary Hemodynamics
		Pathology of RV Failure
		Molecular Mechanisms of RV Failure
			Ischemia and Angiogenesis
			Neurohormonal Activation in RV Failure
			Right Ventricular Metabolism and Mitochondrial Function
			Sex Hormones
			Other Causes of RV Failure
		Genetics of RV Failure
			BMPR2
		RV Failure in Non-group 1 PH
		Future Directions
		References
	3: Experimental Models
		Introduction
		MCT-Induced PAH
		MCT Plus Pneumonectomy
		Hypoxia-Induced PH
		Chronic Hypoxia in Mice
		Chronic Hypoxia in Rats
			Sugen 5416 Plus Chronic Hypoxia in Rats
			Sugen 5416 Plus Chronic Hypoxia in Mice
		Schistosomiasis
		PH Due to Left-Heart Disease
		Myocardial Infarction (MI)
		Transverse Aortic Constriction (TAC)
			Metabolic Syndrome
		Chronic Thromboembolic PH (CTEPH)
		Pulmonary Artery Banding (PAB)
		Other Models
			Smoke-Induced PH
			Intermittent Hypoxia
			Lung Cancer-Associated PH
		Summary
		References
	4: Mechanical and Functional Interdependence Between the RV and LV
		Introduction
		Physiology of RV-LV Interactions
		RV-LV Interactions When the RV Is Hypertensive
		Mechanical-Molecular RV-LV Interactions in RV Hypertension
		RV-LV Interactions at the Septal Hinge-Point Regions
		Therapeutic Targeting of Molecular-Tissue RV-LV Interactions in RV Hypertension
		RV-LV Interactions in Congenital Heart Disease
		Summary
		References
Part II: Imaging the Right Heart
	5: MRI of the Right Ventricle in Normal Subjects and Those with Pulmonary Hypertension
		Introduction
		Measuring Ventricular Volumes, Mass and Global Function
			Measuring Regional Right Ventricular Function: Myocardial Tagging and Strain Mapping
			CMR-Guided Right-Heart Catheterisation
			Defining Normal Values for Right Ventricular Mass and Volume
			Factors Affecting Normal Values: Scaling Right Ventricular Size and Function for Body Size
				Ageing and the Right Ventricle
				Sex
				Race
				Physical Activity (in the Non-athlete)
				Obesity
				Normative Equations for RV Variables
		Role of CMR in the Diagnosis and Management of Patients with Pulmonary Hypertension
			Diagnosis of Pulmonary Hypertension
			Effects of Pulmonary Hypertension on Cardiac Structure: Measurements by CMR
				RV (and LV) Mass/Volumes/Damage
			Effects of Pulmonary Hypertension on Cardiac Function: Measurements by CMR
				RV-PA Coupling
				Global vs. Regional Cardiac Function in PH
				Myocardial Perfusion
			Treatment of Pulmonary Hypertension: Efficacy Measured by CMR
		Conclusion
		References
	6: Right Ventricular Structure and Function During Exercise
		Introduction: Why Is Right Ventricular Function Important During Exercise?
		Physiology of the RV and Pulmonary Circulation and Its Relevance to Exercise
		Exercise Causes a Disproportionate Increase in RV Pressures, Wall Stress and Work
		How Can RV Function Be Assessed During Exercise?
		Can the Healthy RV Cope with the Increased Pulmonary Vascular Load of Exercise?
		Clinical Settings in Which the Assessment of RV Function During Exercise May Be Important
			Athletes
			Chronic Pulmonary Disease
			Pulmonary Vascular Pathology
			Heart Failure
			Valvular Heart Disease
			Congenital Heart Disease
		Can Pulmonary Vasodilators Improve Exercise Tolerance?
		Conclusions
		References
	7: Echocardiography of the Right Heart
		Introduction
		Measurement of the Pulmonary Pressures and Cardiac Output
		Accuracy of Echocardiographic Measurements of the Pulmonary Circulation
		RV Systolic Function and RV-Arterial Coupling
		Echocardiographic Indices of RV Systolic Function
		RV Systolic Function Assessed by 3D Echo and 3D Right Ventricular Ejection Fraction
		RV Dimensions, Remodeling, and Diastolic Function
		RV Dyssynchrony
		Conclusions
		References
Part III: Causes of Right Heart Dysfunction
	8: Volume Overload and the Right Heart
		Introduction
		Overview of RV Volume Overload
			Anatomic and Functional Adaptation to RV Volume Overload
			Cellular and Molecular Adaptation to RV Volume Overload
			Clinical Course and Management of RV Volume Overload
		Specific Etiologies of RV Volume Overload
			Tricuspid Regurgitation
			Pulmonary Regurgitation
			ASD/PAPVR
		Conclusions
		References
	9: Right Ventricular Response to Pulmonary Arterial Hypertension and Chronic Thromboembolic Pulmonary Hypertension
		Introduction
		RV Responses to Load
			RV Remodeling in Pulmonary Arterial Hypertension of Congenital Heart Disease
			RV Remodeling in Chronic Thromboembolic Hypertension
		Assessment of RV Contractility
			Echocardiography
			Cardiac Magnetic Resonance Imaging
			Pressure-Volume Loops
				End-Systolic Elastance as a Measure of RV Contractility
				Pulmonary Arterial Elastance as a Measure of Afterload
				Preload Recruitable Stroke Work as a Measure of Contractility
		Alterations in RV Contractility and Ventricular-Arterial Coupling in PAH and CTEPH
			Pressure-Volume Loop Evaluation of RV-Pulmonary Arterial Coupling
			RV-PA Coupling Predicts Outcomes in PAH
			Echocardiography Evaluation of RV-Arterial Coupling
			cMRI Evaluation of RV-PA Coupling
		RV-PA Coupling and Disease
			RV-PA Coupling in Idiopathic PAH and Systemic Sclerosis-Associated PAH
			RV-PA Coupling in Congenital Heart Disease
			RV-PA Coupling in CTEPH
			Sex Differences in RV-PA Coupling
			RV Reserve
		Mechanisms Underlying Maladaptive RV Adaptation in PAH
			Macro- and Microvascular RV Ischemia
			Metabolic Shifts in the RV Myocardium
			Neurohormonal Activation
			Metabolic Syndrome and RV Remodeling
		RV Diastolic Dysfunction in PAH and CTEPH
		Conclusion
		References
	10: Left-Heart Failure and Its Effects on the Right Heart
		Introduction
		Causes of Right-Heart Dysfunction in HFrEF Patients
		Causes of Right-Heart Dysfunction in HFpEF Patients
		Gaps in Evidence and Perspectives
		Conclusions
		References
	11: Cor Pulmonale
		Introduction
		Physiological Reminders
		Diagnosis of Cor Pulmonale
		Treatment of Cor Pulmonale
		References
	12: High Altitude and the Right Ventricle
		Introduction
		Definitions
		Altitude as a Cause of Increased RV Afterload
		Does Hypoxic Exposure Exert Negative Inotropic Effects?
		The Right Ventricle During Hypoxic Exercise
		High Altitude-Induced Right-Heart Failure
		Perspective
		References
	13: The Right Ventricle in Congenital Heart Diseases
		Introduction
		Lesions Affecting Preload
			Atrial Septal Defect
		Tetralogy of Fallot
			Historical Perspective
			Pulmonary Incompetence
			RV Motion: A Gradient from Base to Apex
			RVOT Akinesia and Dyskinesia
			Dyssynchrony and RV-LV Interaction
			Restrictive RV Physiology
			Outcome and Risk Factors
		The Systemic RV
			The Systemic RV in a Biventricular Circulation: ccTGA and TGA-Senning/Mustard
			TGA and Atrial Switch
			RV Dysfunction in Systemic RV
			Tricuspid Insufficiency
			Dyssynchrony
			Response to Exercise/Stress
			Treatment Options
			Pulmonary Artery Banding and Double Switch
			The Systemic RV in Hypoplastic Left-Heart Syndrome
		The RV in PAH Associated with CHD
		Summary
		References
	14: Pulmonary Embolism
		Introduction
		Mechanisms Regulating Thrombosis
		Epidemiology of Venous Thromboembolism
		Pulmonary Vasculature
		Pulmonary Arterial System Network and the Right Ventricle
		Acute Pulmonary Embolism, Right Ventricular Architecture, and Myocardial Mechanics
		Diagnosis and Assessment of Right Ventricular Function in Acute Pulmonary Embolism
		New Frontiers in the Assessment of Right Ventricular Function in Acute Pulmonary Embolism
		After Acute Pulmonary Embolism Diagnosis
			Risk Assessment
			Imaging
			Prognosis
			Groups at Increased Risk of Recurrence (High at >8%/Year)
			Duration of Anticoagulation
			Chronic Pulmonary Embolism
		Conclusion
		References
	15: Right Ventricular Cardiomyopathies
		Arrhythmogenic Cardiomyopathy
			Historical Notes and First Clinical Descriptions
			Epidemiology
			Pathological Findings
			Genetic Background
				Plakophilin 2 (PKP-2)
				Desmoplakin (DSP)
				Desmoglein 2 (DSG-2)
				Desmocollin 2 (DSC-2)
				Plakoglobin (JUP)
					α-T-Catenin (CTNNA3)
					Cadherin-2 (CDH2)
					Laminin (LMNA)
					Desmin (DES)
					Transmembrane Protein 43 (TMEM-43)
					Titin (TTN)
					Filamin C (FLNC)
					Ryanodine Receptor 2 (RYR2)
					Nav1.5 (SCNA5)
					Phospholamban (PLN)
			Clinical Features and Natural History
		Sports Activity and Arrhythmogenic Cardiomyopathy
			Disease Diagnosis
			Diagnostic Tools in AC
				Personal and Familial Anamnesis
				Twelve-Lead Electrocardiogram (ECG)
				Ventricular Arrhythmia (VA) Detection
		Two-Dimensional Echocardiography
			Advanced Echo Modalities
		Cardiac Magnetic Resonance
			Endomyocardial Biopsy
		Arrhythmogenic Left Ventricular Cardiomyopathy
		Therapeutic Strategies in AC
			Physical Restriction
			Drug Therapy
				Beta-Blockers
				Antiarrhythmic Drugs
				Heart Failure Drugs
				New Drugs
			Catheter Ablation
			ICD Implantation
			Heart Transplant
		Right Ventricular Myocardial Changes in Specific Diseases
			Cardiac Sarcoidosis
			Dilated Cardiomyopathy
			Hypertrophic Cardiomyopathy
		References
Part IV: Treatment of Right Heart Dysfunction
	16: Right-Heart Reverse Remodeling During Treatment for Pulmonary Hypertension
		The Heart Remodeling
		Right Ventricle Response to Chronic Pressure Overload
		The Concept of Reverse Remodeling
		Reverse Right Ventricular Remodeling in Patients with Pulmonary Hypertension: The Effect of Ventricular Unloading
		The Evaluation of Right Ventricular Reverse Remodeling
		The Impact of PAH-Specific Therapies on RV Reverse Remodeling
		References
	17: Acute Right-Heart Failure in Patients with Chronic Precapillary Pulmonary Hypertension
		Introduction
		Pathophysiology of Right-Heart Failure
			Acute Right-Heart Failure Decompensation
		Epidemiology of Acute Decompensated Pulmonary Hypertension and Prognosis
		Treatment of RHF in ICU
			Identification and Management of Triggering Factors
			Fluid Status Optimization
			Cardiac Output and Blood Pressure Optimization
			RV Postload Optimization
			Management of Refractory Right-Heart Failure
				Urgent Lung and Heart-Lung Transplantation in Pulmonary Hypertension
				Extracorporeal Life Support in Acute Decompensated Pulmonary Hypertension
		Monitoring of Acute RHF in PH Patients
			Clinical Monitoring
			Circulating Biomarkers
			Noninvasive Hemodynamic Evaluation
			Invasive Hemodynamic Monitoring
		Conclusion
		References
	18: Cardiac and Lung Transplantation and the Right Heart
		Introduction
		Donor Right Ventricular Failure in Cardiac Transplantation
		Prediction of Risk of RV Failure in a Cardiac Transplant Candidate
			Interpretation of Initial Hemodynamics
			Pulmonary Artery Diastolic Pressure to Pulmonary Capillary Wedge Gradient
		Acute Modulation of Hemodynamics
			Acute Vasoreactivity Testing
			Subacute Efforts to Improve Pulmonary Hemodynamics
			Left Ventricular Assist Devices to Improve Pulmonary Hemodynamics
			Lung and Heart-Lung Transplantation in Pulmonary Hypertension
			Cardiac and Noncardiac Pathophysiology of the Advanced PAH Patient
			Timing of Lung Transplantation in PAH1
		Factors Relevant to a Previously Compensated Patient Who Suffers Abrupt Deterioration
		Conclusions
		References
	19: Arrhythmias in Right-Heart Failure due to Pulmonary Hypertension
		Introduction
		Pathophysiology
		Supraventricular Arrhythmias
		Therapy
		Ventricular Arrhythmias
		Conclusion
		References
	20: Atrial Septostomy
		Introduction
		Rationale
		Theoretical Background
		Computational Models
		Experimental Models
		Clinical Evidence
		Characteristics of Patients Submitted to Atrial Septostomy
		Safety, Clinical and Hemodynamic Effects of Atrial Septostomy
		Late Effects of Septostomy on Right Ventricular Function
		Effects on Blood Gases and Oxygen Transport
		Risks and Limitation of Atrial Septostomy
		Atrial Septostomy and Therapeutic Strategy in Pulmonary Hypertension
		Atrial Septostomy Plus Dedicated Devices for the Management of HF with Preserved Ejection Fraction
		References
Part V: Future Perspectives
	21: Treating the Right Ventricle Directly in Pulmonary Hypertension
		Introduction
		Drugs Targeting Pulmonary Hypertension That Are Vasodilators and May Have a Pressure-Independent Effect on the Right Ventricle
		Myocardial Capillaries and Fibrosis in Right Ventricular Failure
		Lessons Learned from Solving Hemodynamic Problems in Children with Congenital Cardiac Abnormalities
			Reverse Potts Shunt
			Lessons Learned: Age- and Disease-Related RV Function
		Conclusions and Outlook
		References
Index