Pathologie et conséquences cliniques de l`insuffisance cardiaque

Pathologie et conséquences cliniques
de l’insuffisance cardiaque droite
Septième Symposium de la
Société Québécoise d’Insuffisance Cardiaque
François Haddad, MD, FRCPC, FACC
Clinical Assistant Professor of Medicine
Division of Cardiovascular Medicine
Stanford University
Disclosures
No disclosures
Plan
1) Historical Perspective on the Right Ventricle
2) Key Features of RV Anatomy and Physiology
3) The Right Heart Failure Syndrome
Historical Perspective
Historical Perspective
`Thus the right ventricle may be said to be made
for the sake of transmitting blood through the
lungs, not for nourishing them.`
Harvey W. De Motu Cordis 1616
The Dispensable RV
Animal studies in 1940-1960s
The Fontan circulation
Kagan A, Circulation 1952
Fontan F , J Thorac Cardiovasc Surg 1983
The Essential RV
Goldstein et al., Circulation 1982
The Essential RV
Goldstein et al., Circulation 1982
The Essential RV
Mehta et al., J Am Coll Cardiol, 2001
Study
Pop.
NYHA
n
Criteria
Main findings
Polak,
1983
CAD
II-IV
34
RVEF < 35%
23% survival ( RVD) vs
71 % survival at 2 years
Di Salvo,
1995
CAD
IDC
III-IV
67
RVEF < 35%
RVD and % VO2 independent
predictors of survival at 2 years
De Groote
1998
CAD
IDC
II-III
205
RVEF < 35%
RVD, maximal VO2, NYHA
independent predictors of
survival at 2 years.
Ghio,
2001
CAD
IDC
III-IV
(70%)
377
RVEF < 35%
Incremental value of PAP and
RV function in predicting event
free survival.
Sun,
1997
IDC
III-IV
(74%)
100
RV area/LV
area > 0.5
RV enlargement independent
predictor of survival
Meluzin,
2005
CAD
IDC
II-IV
140
RVMPI > 1.20
IVA < 2.52 TAV
< 10.8
RVMPI and TDI were
predictive of mortality or eventfree survival.
RV dysfunction in Heart Failure
Ghio et al. J Am Coll Cardiol, 2001
Clinical Importance in PAH
Alonzo et al. Ann Int Med, 2001
Prognostic Value of BNP in IPAH
Nagaya et al, Circulation 2000.
Right Ventricular Adaptation to Disease
Several studies have shown that right ventricular
adaptation to pressure or volume overload is the most
important predictor of outcome.
Clinical Significance of Right Heart
Failure in Cardiac Surgery
•
Post-cardiotomy refractory RHF: 0.04 to 0.1%
•
Acute refractory RHF post heart transplant in 2-3%
•
Acute refractory RHF in almost 20-30% patients who
receive LVAD.
Maslow et al, Anesth Analg 2002
Kaul et al,Cardiovas Surg 2000
Circulation. 2006;114:1883-1891
The Helical Ventricular Myocardial Band
Torrent-Guasp et al., JCTS 2001.
Torrent-Guasp et al., JCTS 2001.
Heart Fields
Buckingham et al., Nature 2005.
Function of the RV
Primary function:
To receive venous return from the systemic circulation
To pump it into the pulmonary system
Under normal circumstances,
RV and LV connected in series, and SV ( RV) ≈ SV (LV)
Pulmonary vascular system is a low resistance-impedance,
highly distensible system.
RV Physiology
1)
Mechanical aspects of RV contraction
2)
Cardiodynamics
3)
Ventricular interdependence
4)
Coronary perfusion
Mechanisms of RV Contraction
1)
Inward movement of the free wall -> bellow effect
2)
Contraction of the longitudinal myofibers which draw
the tricuspid annulus towards the apex
3) Traction of the free wall to their point of attachment to
the Left Ventricle
Determinants of RV function
RV ejection depends on:
1) Contractility
2) Preload
3) Afterload
4) RV geometry
5) Ventricular interdependence
6) Ventricular synchrony
7) Valvular regurgitation or shunt physiology
Holy Grail of Ventricular Physiology
Finding an index of ventricular function that is
independent of loading conditions
Especially important in Right Heart Disease where the
loading conditions are often abnormal. The hope is that
such an index would better predict long term survival or
recovery after corrective surgery
Ideal index of contractility
1) Sensitive to change in inotropy
2) Independent of loading conditions
3) Independent of heart size and mass
4) Easy and safe to apply
5) Proven to be useful in the clinical setting
Carabello BA. Evolution of the study of left ventricular function: everything old is new again.
Circulation 2002
Pressure Volume Curve
Pressure
Telesystolic pressure
Ejection volume
Telediastolic pressure
Volume
Telesystolic volume
Telediastolic volume
Time Varying Elastance Model of RV
Champion et al., Circulation, 2010
Non-invasive indices of Ventricular Function
1) Volumetric or dimension based indices
2) Time Phase indices
3) Derivative of Pressure or time (dP/dt)
4) Tissue Velocity, strain or stain rate
5) Combined indices
TAPSE
Echo Evaluation of RV Function
Myocardial Performance Index
Miller, et al. JACC 2004;17:443-447
Echo Evaluation of RV Function
Measurement of dP/dtmax and IVA during pacing in 8
animals
Vogel, M. et al. Circulation 2002
Functional parameters
Normal value
Load
dependence
RVEF (%)
61±7 % (47-76%)
> 40-45%
+++
RVFAC (%)
> 32%
+++
TAPSE (mm)
> 15
+++
Sm annular
(cm/s)
> 12
+++
Strain
Basal : 19±6
Mid : 27±6
Apical : 32±6
+++
Strain rate (s-1)
Basal: 1.50±0.41
Mid: 1.72±0.27
Apical : 2.04±0.41
++
RVMPI
0.28± 0.04
++
dp/dt max (mmHg/s)
100-250
++
IVA (m/s2 )
1.4 ± 0.5
+
Maximal RV elastance
(mmHg/ml )
1.30±0.84
+
Diastolic Parameters
Right ventricular filling
Starts before and finishes
after LV filling.
Rapid filling velocity (E):
lower
Deceleration time of E:
longer
E/A ratio:
smaller
Length of atrial contraction:
longer
Isovolumic contraction period:
shorter
Respiratory changes:
increased
Models of Pulmonary Circulation
Indices of Afterload
Index of Afterload
Index of
afterload
Comment
Pulmonary pressure
+
Easy to measure
Pulmonary vascular
resistance (PVR)
++
Takes into account
flow and pressure
Pulmonary capacitance
++
Takes into account
compliance
Pulmonary Impedance
+++
Combined index but
more difficult to
measure
Models of Pulmonary Circulation
Naeije, Pulmonary Circulation, 2004
Ventricular Interactions
Ventricular interactions is defined as the influence
of the structure and function of one ventricle on the
other ventricle
Secondary to :
-Anatomical factors: refers to ventricular interdependence
-Circulatory factors: pulmonary hypertension
-Neurohormonal factors: NE, BNP, RAAS, endothelin
Belenkie et al., Ann Med 2001
Ventricular Interdependence
Size, shape, compliance of one ventricle affect size,
shape, P-V relationship of the other ventricle.
Anatomical substrate:
- Shared septum
- Shared muscles bundles
- Common pericardium
Diastolic Interdependence
Dell’Italia, NEJM, 1998
Systolic Interdependence
1)
Systolic interdependence is mediated mainly by the
interventricular septum
2)
The pericardium is not as important as for diastolic
interdependence
3)
The LV could contribute to 20 to 40 % of RV systolic
pressure in the absence of a dilated RV
4) In the presence of a dilated RV, the efficiency of left to
right interaction is decreased significantly.
Elzinga G et al., Am J physio, 1974
Feneley, Mpet al., Circulation, 1985
Weber, K T et al., Am J Cardio, 1981
RV Circulation and Perfusion
Frank H. Netter, The Heart, CIBA Collection.
Metabolism of the RV
Right Ventricular Failure
Complex clinical syndrome that can result from any
structural or functional cardiovascular disorder that impairs
the ability of the RV to fill or to eject blood
Cardinal Manifestations
1)
Fluid retention, which may lead to peripheral edema,
ascites and anasarca
2)
Decreased systolic reserve or low cardiac output which
may lead to exercise intolerance and fatigue
3) Arrhythmias (supraventricular and ventricular)
Mechanism of RHF
Specific etiology
Pressure overload
Pulmonary hypertension
RVOT obstruction
Double chambered RV
Systemic RV
Volume overload
Tricuspid regurgitation
Pulmonary regurgitation
Atrial Septal defect
Sinus of Valsalva rupture into the RA
Ischemia and infarction
RV myocardial infarction
May contribute to RV dysfunction in CHD*
Intrinsic myocardial process
Cardiomyopathy and HF
Arrhythmogenic right ventricular dysplasia
Sepsis
Inflow limitation
Tricuspid stenosis
Superior vena cava stenosis
Complex congenital defects
Ebstein's anomaly
Tetralogy of Fallot
Transposition of Great Arteries
Pericardial disease
Constrictive pericarditis
RV Adaptation to Disease
- Importance of timing:
Time of onset ( congenital vs. acquired)
Time course (acute vs. chronic)
- Type of overload
In general the RV adapts better to volume than to
pressure overload.
- Neurohormonal and immunological factors
- Genetic Factors
Litherson, R. et al., Am J Cardiol, 1981.
Hopkins, W. E., J Heart and lung Transplant, 1996
Right ventricular dysfunction
Ventricular
Interdependence
Arrhythmia
Systolic and diastolic
LV dysfunction
Compression of LM
by pulmonary artery
in PH patients (rare)
Diastolic dysfunction
Systolic dysfunction
TR
Low cardiac output
Circulatory failure
Right to left shunt
Myocardial
Ischemia
Hypoxemia
Congestive component
Congestive hepatopathy
( cirrhosis possible)
Protein losing enteropathy
Fluid retention
Genetic Factors
Abraham et al., Journal of renin-angiotensin-aldosterone, 2002.
Cellular Mechanisms
Nagendran, Circulation, 2007
Specific Molecular Pathways
Active Areas of Investigation
1- Phenotypic characterization
2- Role of Matrix Remodelling
3- Role of Mitochodrial Function
4- Role of micro-RNA
5- Oxidative Stress
6- Importance of Apoptosis
Management
1) Should always take into account:
- the cause and setting of RVF
- the severity of RVF
2) Goal is to optimize RV preload, afterload and contractility
3) In acute RVF, hypotension should be avoided
4) Evidence is less well established than in HF with LV
dysfunction
Stages of RV failure
Hunt et al, ACC/AHA Guidelines HF, 2005
Potential Breakthrough Areas
Early diagnosis of PH
Defining novel indices of right heart function
Conduit engineering for CHD
Understanding mechanisms (e.g.microRNA,mitochondrial
medicine, genomics) and its clinical and therapeutic
implications
Mechanical Support of the failing RV
Targeted RV therapy
Research Effort
Pulmonary Hypertension
Jeffrey Feinstein
David Rosenthal
Roham Zamanian
Kristina Kudelko
Vinicio De Jesus Perez
Heart Failure
Euan Ashley
Randy Vagelos
Michael Fowler
Pulmonary Medicine
David Weill
Gundeep Dhillon
Rama Sista
Mark Nichols
Heart Transplant
Sharon A Hunt
Michael Pham
Hannah Valantine
Thu Vu
Congenital Heart Disease
Daniel Murphy
Joe Wu
Cardiac Surgery
Bruce Reitz
Robert Robbins
Philip Oyer
Tobias Deuse
Imaging
Ingela Schnittger
Phil Yang
Michael McConnell
Shahriar Heidary
Basic Science
Joe Wu
Daniel Bernstein
Euan Ashley
Marlene Rabinovitch
Collaborators
Haissaim Haddad
André Denault
Paul Hassoun
Patrick Fisher
Acknowledgements
Sharon A. Hunt, MD, MACC
Michel White, MD, FACC
André Y. Denault, MD PhD, FRCPC
Euan Ashley, MB DPhil, FACC
David N. Rosenthal, MD, FACC
Evangelos Michelakis, MD, FACC