Left Ventricular Pump Function
Michael R. Pinsky, MD, Dr hc Department of Critical Care Medicine University of Pittsburgh Left Ventricular Pump Function
• Maintain a constant and high organ input pressure • Eject Stroke Volume into a low compliance high resistance arterial circuit • Transfer all blood received with a minimal back pressure • Match cardiac output to venous return on a beat-to-beat basis Bedside Assessment of Ventricular Pump Function Assessing Left Ventricular Performance Commonly Used Measures of Cardiovascular Function:
Heart Rate Blood Pressure Cardiac Output Stroke Volume LV ejection fraction Frank-Starling Relationship
• Frank: Force of fiber contraction proportional to length prior to excitation • Frank. Z Biol 32:370-437, 1895 • Starling: Fiber length proportional to end-diastolic volume • Patterson & Starling. J Physiol (Lon) 48:465-513,1914 • Frank-Starling: Systolic function proportional to end- diastolic volume Primacy of Preload in Determining Systolic Performance Otto Frank Isometric contractions of a frog ventricle at increasing filling pressures Frank O, Z Biol 1895; 32:370 Ernest Starling Stroke volume increases with end-diastolic volume
End-diastolic Volume
Increased End-diastolic Volume
Patterson & Starling. J Physiol 48:357-87, 1914 Starling versus Anrep Heterometric v. Homeometric autoregulation of the heart
Increased Preload Starling EDV Preload Afterload Heart Rate Anrep Contractility
ESV Increased Contractility
Sudden increase and decrease in venous return Rosenblueth et al. Arch Int Physiol 67: 358, 1959 Frank-Starling Relationship
LV Ejection Hyper-effective Phase Indies:
Ejection Fraction Stroke Volume Stroke Work Hypo-effective LV dP/dt
Vcf Preload (end-diastolic volume)
Sarnoff & Berglund. Circulation 9:706-18, 1954 Frank-Starling Relationship Is heart A “better” than heart B? A
B Stroke Volume Stroke
Preload (end-diastolic volume) Arterial pressure increases with end-diastolic volume
Patterson & Starling. J Physiol (London) 48:357-79, 1914 Inherent Weaknesses with Using Stroke Volume as a Measure of Cardiac Contractility
• Stroke volume is altered by Ejection Pressure • Increasing arterial pressure decreases stroke volume • Decreasing arterial pressure increases stroke volume • Stroke volume is altered by Heart Rate • Tachycardia decreases stroke volume (less filling time) • Bradycardia increases stroke volume (more filling time) • Chronotropy For a constant end-diastolic volume: • Increasing heart rate increases stroke volume • Decreasing heart rate decreases stroke volume Ventricular Function
Muscular Work LV ejection: volume under pressure
Stroke Work = Developed Pressure x Stroke Volume
Minute Work = Stroke Work x Heart Rate Frank-Starling Relationship
A
B Stroke Work Stroke
Preload (end-diastolic volume) Wiggers CJ, Circulation 5:321-48, 1952 LV Pressure-Volume Loop End-systole Ejection (stroke volume) Aortic Valve Opening LV Isometric Isometric Pressure Relaxation Contraction (mm Hg)
Mitral Valve End-diastole Opening Diastolic filling
LV Volume (mL) Patterson & Starling. J Physiol 48:465-513,1914 Determinants of LV Function Preload End-diastolic volume Afterload Systolic wall stress Contractility Intrinsic myocardial performance Heart Rate Chronotropy
Patterson & Starling. J Physiol 48:357-79, 1914 Frank-Starling Relation Primacy of PRELOAD in determining ventricular systolic performance
Preload is determined by systemic venous return Preload is the primary determinant of cardiac output
LV Preload equals LV end-diastolic volume
Patterson & Starling. J Physiol 48:465-513,1914 LV Pressure-Volume Relations Diastolic Filling
LV Diastolic Compliance = P/ V Pressure End-diastolic P/V Relation Increased (mm Hg) Stiffness
P V
LV Volume (mL) Pinsky Intensive Care Med 29:175-8, 2003 Isometric LV Ejection
End-Systolic Developed Pressure LV Pressure (mm Hg) A B C
LV Volume (mL) Suga et al. Circ Res 32:314-322, 1973 Isometric LV Ejection
End-Systolic Pressure- Volume Relationship
LV Pressure (mm Hg) A B C
LV Volume (mL) Suga et al. Circ Res 32:314-322, 1973 LV Ejection from a Common EDV
End-Systolic Pressure- C Volume Relationship
LV B Pressure (mm Hg) A
LV Volume (mL) Suga et al. Circ Res 32:314-322, 1973 Isometric LV Contraction or Ejection
Suga et al. Circ Res 32:314-322, 1973 The Slope of the End-Systolic Pressure-Volume Relationship (ESPVR) is proportional to contractility
• The ESPVR is relatively insensitive to loading conditions • Independent of prior end-diastolic volume • Independent of subsequent ejection pressure • Increasing ESPVR is increased contractility • Decreasing ESPVR is decreased contractility
Suga et al. Circ Res 32:314-322, 1973 LV Pressure-Volume loops at variable venous return before and after epinephrine
Suga et al. Circ Res 32:314-322, 1973 Effect of Changes in Contractility on the End-Systolic Pressure-Volume Relationship Decreased Contractility Increased Contractility
Augmented Normal LV Pressure Failure (mm Hg)
LV Volume (mL) Suga et al. Circ Res 32:314-322, 1973 The Functional Basis for Left Ventricular Contraction and ESPVR
LV pressure-volume histories at differing preloads and afterloads LV Pressure
LV Volume On the Nature of LV Contraction Sequential P/V Loops during IVC Occlusion
IVC LV Occlusion Pressure
LV Volume End-Systolic Pressure Volume Relationship (generated by IVC occlusion)
Ees IVC Occlusion
Ejection
Diastolic compliance On the Nature of LV Contraction Iso-chronic lines at 20 ms intervals
200 140 100 80
ESPVR 60
LV 40 Pressure 20
LV Volume Suga et al. Circ Res 32:314-322, 1973 On the Nature of LV Contraction
Iso-chronic lines at 20 ms intervals Baseline Increased Inotrophy (Epinephrine infusion) 100 80 60 200 140100 40 80 60 P P 40 20 20
Volume Volume Suga et al. Circ Res 32:314-322, 1973 Time-Varying Elastance (Et) Instantaneous LV Pressure/Volume Relations
Increased Contractility
(Epinephrine) (mmHg/ml)
Normal LV P/V P/V LV Contractility (Baseline)
Time (sec) Suga et al. Circ Res 32:314-322, 1973 On the Nature of LV Contraction
Time-Varying Elastance (Et) • Shortening proceeds uniformly from start to end of systole independent of either pressure or volume • Time post-initiation of systole defines a pressure- volume domain which is independent of history
• Increased contractility increases Et throughout systole • Increased contractility decreases the time to end- systole Suga et al. Circ Res 32:314-322, 1973 Time-varying Elastance
(Et)
• All events characterized by the Frank- Starling Relationship can be explained
completely by the concept of Et • Preload “appears” to be determining
systolic function because Et has an increasing slope over time
Suga et al. Circ Res 32:314-22, 1973 On the Nature of LV Contraction Time varying Elastance and the Frank-Starling Relationship 200 140 100 80 60 40
20
Pressure
Ejection Indices
Volume A B A B EDV Stroke volume, ejection fraction, dP/dt All increase with increasing EDV Cardiac Contractility
Contractility proportional to the rate and amount of Ca+2 flux into the sarcolema of the contracting myocytes
All known positive inotropes increase Ca+2 flux All known negative inotropes decrease Ca+2 flux Cardiac Contractility
Since Ca+2 is essential for contraction, is Ca+2 a positive inotrope? Yes and No
Where the Ca+2 goes is as important as how much Ca+ there is available Cardiac Contractility
Changes in contractility reflect LONG TERM adaptations to external stress (Anrep effect) Cardiac Contractility
• Autonomic Tone Exercise, Stress; Diabetes • Coronary Blood Flow • Kojima et al. Am J Physiol 264:H183-9, 1993 • Serum ionic Ca+2 • Marquez et al. Anesthesiology 65:457-61, 1986 • Local Catecholamine Stores Chronic stress • Catecholamine Receptors Sepsis • Extrinsic Catecholamine Supplements Assessing LV Contractility at the Bedside
• LV dP/dt at 20 or 30 mmHg • Prior to aortic value opening • Preload, heart rate and afterload dependent
• Can radial arterial dP/dtmax reflect LV contractility? • Reflected pressure waves distort arterial pressure • Compliance and inertance alter peripheral pressure
• Compared LV dP/dtmax with femoral and radial arterial dP/dtmax as contractility, preload and afterload systematically altered in pigs
Monge Garcia et al. Crit Care 22 325, 2018 Changes in Radial Artery dP/dtmax Tracks Changes in Ees
DVasomotor D Volume D Contractility
Monge Garcia et al. Crit Care 22 325, 2018 Determinants of Afterload
LaPlace’s Law LV Wall Stress
Tension = Px r r P Maximal tension at maximal P x r which usually occurs at the opening of the aortic value: EDV, diastolic pressure Chronotropy
Increases in heart rate increase Ca+2 influx into the sarcolema of the myocytes increasing force of contraction
Bers. Nature 415:198-205, 1998
Optimal heart rate? > 60 but < 120 Effect of Changes in Heart Rate on Contractility Force-Frequency Relationship
Liu et al. Circulation 88:1893-906, 1993 Effect of Changes in Heart Rate on Contractility Force-Frequency Relationship
70 min-1 100 min-1 70 min-1 100 min-1
Chronotropy Diastolic Dysfunction 130 min-1 160 min-1 120 min-1 150 min-1
Liu et al. Circulation 88:1893-906, 1993 What is heart failure? 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 Type I: Heart failure because of an increase in loading conditions
Preload: valvular incompetence, arterio-venous fistulas, anemia, sepsis, hypervolemia, beri beri Afterload: hypertension, aortic stenosis, sepsis Type II: Heart failure because of a decreased contractility
Myocardial infarction Ischemic heart disease Dilated cardiomyopathy infections, metabolic alterations, toxic conditions, collagen vascular disease Idiopathic dilated cardiomyopathy Type III heart failure: restriction to ventricular filling: Diastolic Dysfunction
Internal: Hypertrophic cardiomyopathy Restrictive cardiomyopathy Incomplete relaxation External: Tamponade Right ventricular dilatation/hypertrophy Functional tamponade (PEEP) Sepsis Clinical Applications of LV Pressure-Volume Relations
Acute Myocardial Ischemia • Useful in understanding the pathophysiolgy of acute myocardial ischemia • Explains rationale for pharmacological approaches to optimize ventricular pump function Effect of Acute Myocardial Ischemia on Left Ventricular Pressure-Volume Relationship Ischemia
LV Ees Ees Pressure Acute LV (mm Hg) Failure
Ischemia
LV volume (mL) Effect of Inotropic Support following Acute Myocardial Ischemia
Ees
LV Ees Pressure (mm Hg) Dobutamine
LV volume (mL) Effect of Vasodilator Therapy & Inotropic Support following Acute Myocardial Ischemia
Ees Ees Decreased LV LV ejection Pressure Pressure (mm Hg)
Nitroprusside
LV volume (mL) Transesophageal Echocardiography-ABD and LV Pressure
Gorcsan et al. Circulation 1994;89:180-90 LV Contractile Reserve in Sepsis Decreased Adrenergic Depressed Responsiveness? 30 contractility? *
20
Baseline E’es Dobutamine 10
0 P < 0.05 Day 1 Day 5 Day 9 n = 10
Cariou et al. Intensive Care Med 34: 917-22, 2008 Effect of Pressure and Volume
Loading on MVO2 and SWlv Pressure load Volume load SWlv MVO2
Cardiac Output Relation Between the LV Pressure-Volume Loop,
MVO2, and Cardiac Efficiency
The hidden mechanical Elastance-Defined work of the LV Potential Work
Stroke Pressure Work
PE
Volume Suga et al.Am J Physiol 240:H39-H44, 1981 The LV Pressure-Volume Area (PVA)
Strok PVA PVA
e LV LV
Work Pressure
Pressure PE
MVO LV Volume LV Volume 2
Suga et al.Am J Physiol 240:H39-H44, 1981 The LV Pressure-Volume Area (PVA)
Suga et al.Am J Physiol 240:H39-H44, 1981 Relation Between the LV Pressure-Volume Loop,
MVO2, and Cardiac Efficiency
MVO2 A >> MVO2 B
A
B LV Pressure LV
LV Volume Relation Between the LV Pressure-Volume Loop,
MVO2, and Cardiac Efficiency
Two P/V loops: Same SW (area) Different PVA & Different MVO 2 MVO2 A >> MVO2 B
A A
B B
LV Pressure LV LV Pressure LV
LV Volume LV Volume The LV Pressure-Volume Area (PVA) and LV Ejection Efficiency
Suga et al.Am J Physiol 240:H39-H44, 1981 Myocardial Efficiency
Myocardial Efficiency = SW/(PVA) x HR
A Goal of Hemodynamic Therapy: Maximize the Extrinsic Work While Minimizing Elastance-Defined Potential Work and Heart Rate Myocardial Efficiency
Myocardial Efficiency = SW/(PVA) x HR
Vasodilator therapy Inotropic support that reduces EDV VentricularParameters Function
Left Ventricular Pressure 0 0 Ees ≈ ESP/ESV Left Ventricular Volume PE Ees SVlv SW SW/(SW+PE) LVefficiency = SW+ PE=LV PVA= MVO 2 Ventricular Pump Function Conclusions
Cardiac output and stroke volume are insensitive measures of intrinsic contractility Difficult to assess cardiac contractility by a single data set, need to follow trends and response to interventions
Time-varying elastance, end-systolic elastance, and preload-recruitable stroke work are the standards for assessing intrinsic myocardial contractility
Radial arterial dP/dtmax trends LV Ees