Pathologie et conséquences cliniques de l’insuffisance ... · PDF fileRV Physiology . 1) Mechanical aspects of RV contraction 2) Cardiodynamics 3) Ventricular interdependence 4)

Pathologie et conséquences cliniques de l’insuffisance cardiaque droite

François Haddad, MD, FRCPC, FACCClinical Assistant Professor of Medicine Division of Cardiovascular Medicine Stanford University

Septième Symposium de la Société Québécoise d’Insuffisance Cardiaque

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

Harvey W. De Motu Cordis 1616

`Thus the right ventricle may be said to be made

for the sake of transmitting blood through the

lungs, not for nourishing them.`

The Dispensable RV

The Fontan circulationAnimal studies in 1940-1960s

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

CADIDC

III-IV 67 RVEF < 35% RVD and % VO2 independent predictors of survival at 2 years

De Groote1998

CADIDC

II-III 205 RVEF < 35% RVD, maximal VO2, NYHA independent predictors of survival at 2 years.

Ghio, 2001

CADIDC

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

CADIDC

II-IV 140 RVMPI > 1.20IVA < 2.52 TAV < 10.8

RVMPI and TDI were predictive of mortality or event-free 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 2002Kaul et al,Cardiovas Surg 2000

Circulation. 2006;114:1883-1891

Torrent-Guasp et al., JCTS 2001.

The Helical Ventricular Myocardial Band

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 circulationTo 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) Contractility2) Preload 3) Afterload4) RV geometry5) Ventricular interdependence6) 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

Pres

sure

Volume

Pressure Volume Curve

Telediastolic volumeTelesystolic volume

Ejection volume

Telediastolic pressure

Telesystolic pressure

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

Miller, et al. JACC 2004;17:443-447

Myocardial Performance Index

Echo Evaluation of RV Function

Vogel, M. et al. Circulation 2002

Measurement of dP/dtmax and IVA during pacing in 8 animals

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±6Mid : 27±6 Apical : 32±6

+ + +

Strain rate (s-1) Basal: 1.50±0.41Mid: 1.72±0.27Apical : 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 accountflow and pressure

Pulmonary capacitance ++ Takes into accountcompliance

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, 1974Feneley, Mpet al., Circulation, 1985Weber, 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 hypertensionRVOT obstructionDouble chambered RVSystemic RV

Volume overload Tricuspid regurgitation Pulmonary regurgitationAtrial Septal defect Sinus of Valsalva rupture into the RA

Ischemia and infarction RV myocardial infarctionMay contribute to RV dysfunction in CHD*

Intrinsic myocardial process Cardiomyopathy and HF Arrhythmogenic right ventricular dysplasiaSepsis

Inflow limitation Tricuspid stenosisSuperior vena cava stenosis

Complex congenital defects Ebstein's anomalyTetralogy of FallotTransposition 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 FactorsLitherson, R. et al., Am J Cardiol, 1981.Hopkins, W. E., J Heart and lung Transplant, 1996

Right ventricular dysfunction

Ventricular Interdependence

Systolic and diastolic LV dysfunction

Compression of LM by pulmonary artery in PH patients (rare)

Systolic dysfunction

Arrhythmia TR

Low cardiac output

Circulatory failure Myocardial Ischemia

Hypoxemia Congestive hepatopathy( cirrhosis possible)Protein losing enteropathyFluid retention

Right to left shunt Congestive component

Diastolic dysfunction

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 contractility3) 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 CHDUnderstanding mechanisms (e.g.microRNA,mitochondrial medicine, genomics) and its clinical and therapeutic implications

Mechanical Support of the failing RVTargeted RV therapy

Research Effort

Pulmonary HypertensionJeffrey Feinstein David RosenthalRoham ZamanianKristina KudelkoVinicio De Jesus Perez

Cardiac SurgeryBruce ReitzRobert RobbinsPhilip OyerTobias Deuse

Congenital Heart DiseaseDaniel MurphyJoe Wu

Heart Failure Euan Ashley Randy VagelosMichael Fowler

Heart TransplantSharon A HuntMichael PhamHannah ValantineThu Vu

Pulmonary MedicineDavid WeillGundeep DhillonRama SistaMark Nichols

ImagingIngela SchnittgerPhil YangMichael McConnellShahriar Heidary

Basic Science Joe Wu Daniel BernsteinEuan Ashley Marlene Rabinovitch

CollaboratorsHaissaim HaddadAndré DenaultPaul Hassoun Patrick Fisher

Acknowledgements

Sharon A. Hunt, MD, MACCMichel White, MD, FACCAndré Y. Denault, MD PhD, FRCPCEuan Ashley, MB DPhil, FACCDavid N. Rosenthal, MD, FACCEvangelos Michelakis, MD, FACC