Working Group of Heart Failure and Cardiac Function Second 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 failure We 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 VO 2 max (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

Frank O. Die Grundform des arteriellen Pulses Z Biol 1899; 37: Ventricular PV curves during ejecting vs non-ejecting beats Isobaric end-systolic PV relationship positioned to the right of the isovolumic end-systolic PV curve indicating strong history- dependence of the end- systolic PV curve – But in 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 ventricle

Volume Pressure Sequential P-V loops Decreased venous return Contractility Emax Pes/Ves Preload = EDV Afterload = PxV or: Pes/SV SV

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

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

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

SV ~ EDVEF = SV / ED increased An increase in preload increases stroke volume

Stroke work increases with end-diastolic volume Patterson 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 initially decreased, then restored with adaptative  EF to increased afterload

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 failure We 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 failure Type 1: increased loading Type 2: altered inotropic state Type 3 altered 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 VO 2 max (or maximum average running speed), because of a limitation in cardiac output

VO 2 = Q x (CaO 2 – CvO 2 ) A VO 2 max is achieved on a bicycle with about half of body’s muscles Minimum CvO 2 is constant – cf HbO 2 dissociation curve, and chronic disease (except sepsis?) does not affect O 2 extraction VO 2 max is determined by maximum O 2 delivery, or cardiac output VO 2 max ~ Qmax x CaO 2 Fleg et al, AHA advisory Circulation 2000;102:15917

Aerobic exercise capacity is determined by O 2 delivery Q x CaO 2 Source: Saltin and Strange, MSSE 1992; 24: 30-37

Linear increase in VO 2 and Q as a function of workload

Exercise testing: linear relationship between VO 2 (or cardiac output) and running speed (workload)

VO 2 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: VO 2 /HR = SV

Rationale for exercise testing to evaluate heart failure -Linear relationships between VO 2, cardiac output and workload, or average running or walking speed -VO 2 max 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 (O 2 delivery, Q x CaO 2 ) to peripheral demand (VO 2 ) 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