Working Group of Heart Failure and Cardiac FunctionSecond Annual Symposium, Woluwe, 14th of October 2006

HEART FAILURE: WHAT CAN A PHYSIOLOGIST TELL THE

CLINICIANS?

Robert Naeije

Erasme University Hospital, Brussels, Belgium

What is heart failureWe define heart failure as a state in

which the heart is unable to meet the demands for blood flow without excessive use of the Frank-Starling mechanism, that is the increase in stroke volume associated with increased preload

Sagawa, Maughan, Suga, Sunagawa.Cardiac Contraction and the Pressure-Volume

Relationship. Oxford University Press, 1988

Definition of Heart Failure

1. Excessive use of the Frank-Starling mechanism: dilated cardiomyopathy and congestion – adaptation vs maladaptation or decompensation

2. Inability to meet peripheral demand: decreased aerobic exercise capacity – decreased VO2max (or maximum average running speed), because of a limitation in cardiac output

Isometric contractions of a frog ventricle at increasing filling pressures O. Frank, Z Biol 1895; 32:370

O Frank 1865-1944

Frank O. Die Grundform des arteriellen Pulses Z Biol 1899; 37:484-526

Ventricular PV curves during ejecting vs non-ejecting beats

Isobaric end-systolic PVrelationship positioned to the right of the isovolumicend-systolic PV curveindicating strong history-dependence of the end-systolic PV curve – Butin canine and human hearts, both curves are superposed

Isovolumic diastolic and systolic PV relationships

Frog ventricle

Squelettal muscle

Dog ventricle

Length-tension relationship applied to the intact ventricleLength-tension relationship applied to the intact ventricle

Volume

Pre

ssu

re

Sequential P-V loops

Decreasedvenous return

ContractilityEmaxPes/Ves

Preload = EDVPreload = EDV

Afterload = PxVAfterload = PxVor: Pes/SVor: Pes/SV

SV

EH Starling in his laboratory, at work on his heart-lung preparation - 1910

Patterson et al, J Physiol (London) 1914; 48:357

Stroke volume increases with end-diastolic volumePatterson et al, J Physiol (London) 1914; 48:357

SV ~ EDV EF = SV / ED increased

An increase in preload increases stroke volume

Stroke work increases with end-diastolic volumePatterson et al, J Physiol (London) 1914; 48:357

An increase in blood pressure decreases stroke volume (1)which is restored by a an adaptative increase in EDV (2)

SV is initiallySV is initiallydecreased, then decreased, then restored with restored with adaptative adaptative EF EFto increasedto increasedafterloadafterload

1: increased contractility 2: decreased contractility

A decrease in contractility decreases stroke volume

Starling ’s law of the heart

Now here are two conditions in which the work of the heart is increased and in which this organ adapts itself by increasing the chemical changes in its muscle at each contraction to the increased demands made upon it. It is evident that there is one factor which is common to both cases, and that is the increased volume of the heart when it begins to contract. So we may make the following general statement. Within physiological limits, the larger the volume of the heart, the greater are the energy of its contraction and the amount of chemical change at each contraction.

EH Starling. The Linacre lecture on the law of the heart.

London: Longmans, Green, 1918

After 60 s of increased loading conditions, return to initial state is associated with decreased EDV and ESV, suggesting increased contractility Patterson et al, J Physiol (London) 1914; 48:357

Heterometric vs homeometric autoregulation of the heart

Source: Rosenblueth et al. Arch Int Physiol 1959; 67: 358

Heterometric vs homeometric autoregulation of the heart

Limitations to Starling’s law of the heart

• Frank-Starling’s law of the heart states that ventricular stroke work increases as a function of end diastolic volume

• This is valid for the rapid adaptation of flow output to changing loading conditions

• Otherwise, the essence of ventricular adaptation to loading conditions is homeometric (systolic function, Anrep’s relationship) rather than heterometric (change in dimensions, Starling’s relationship)

What is heart failureWe define heart failure as a state in

which the heart is unable to meet the demands for blood flow without excessive use of the Frank-Starling mechanism, that is the increase in stroke volume associated with increased preload

Sagawa, Maughan, Suga, Sunagawa.Cardiac Contraction and the Pressure-Volume

Relationship. Oxford University Press, 1988

Heart failureType 1: increased loadingType 2:altered inotropic stateType 3altered lusitropic state

Sagawa, Maughan, Suga, Sunagawa.

Cardiac Contraction and the Pressure-Volume Relationship. Oxford University Press, 1988

Definition of Heart Failure

1. Excessive use of the Frank-Starling mechanism: dilated cardiomyopathy and congestion – adaptation vs maladaptation or decompensation

2. Inability to meet peripheral demand: decreased aerobic exercise capacity – decreased VO2max (or maximum average running speed), because of a limitation in cardiac output

VO2 = Q x (CaO2 – CvO2)

• A VO2max is achieved on a bicycle with about half of body’s muscles

• Minimum CvO2 is constant – cf HbO2 dissociation curve, and chronic disease(except sepsis?) does not affect O2 extraction

• VO2max is determined by maximum O2 delivery, or cardiac output

VO2max ~ Qmax x CaO2

Fleg et al, AHA advisory Circulation 2000;102:15917

Aerobic exercise capacity is determined by O2 delivery Q x

CaO2

Source: Saltin and Strange, MSSE 1992; 24: 30-37Source: Saltin and Strange, MSSE 1992; 24: 30-37

Linear increase in VOLinear increase in VO22 and Q as a function of workload and Q as a function of workload

Exercise testing: linear relationship between VOExercise testing: linear relationship between VO22 (or cardiac (or cardiac

output) and running speed (workload)output) and running speed (workload)

VOVO22max and the Cooper test (12 min run)max and the Cooper test (12 min run)

Cooper et al, JAMA 1968; 203: 201-4

Six-min Walk Distance and CPET in heart failure

Miyamoto et al, AJRCCM 2000; 161: 487-492

VO2/HR = SV

Rationale for exercise testing to evaluate heart failure

- Linear relationships between VO2, cardiac output and workload, or average running or walking speed

- VO2max or 6MWD exclusively determined by maximum cardiac output, - or the ability of systolic function to cope with increased afterload

- This is why the 6MWD is correlated to functional class, survival, and clinical state, and is sensitive to therapeutic interventions

Fleg et al, AHA advisory Circulation 2000;102:15917

Conclusions

• A sound definition of heart failure rests on the notion of changes in loading conditions and/or relative insufficiency of systolic/diastolic adaptation, as a cause of insufficient flow output (O2 delivery, Q x CaO2) to peripheral demand (VO2)

• Associated changes in ventricular dimensions and diastolic function may be a cause of congestion

• Heart failure is a continuum, with uncertain significance of clinical notions of compensation or decompensation