Ventricular pump function is often compromised during critical illness and for a variety of reasons. The most common cause of a limited cardiac output in acutely ill patients is right ventricular (RV) dysfunction. Exacerbations of chronic obstructive lung disease or the use of high end-expiratory pressure sin acute lung injury to support arterial oxygenation can result in acute elevations of pulmonary arterial pressure impeding RV ejection, causing RV dilation, decreased left ventricular (LV) diastolic compliance. All these effects limit cardiac output and LV stroke volume. Importantly, the treatment is to sustain mean arterial pressure greater than pulmonary artery pressure to prevent RV ischemia and balance RV fluid status to avoid both over-distention (acute cor pulmonale) and under-filling. This delicate fluid balance is greatly facilitated by the immediate and repeated use of bedside echocardiography. Attempts to minimize lung over distention should be a primary focus of therapy.  If one focuses only on the LV, these patients would be said to have a reversible form of diastolic dysfunction, in that LV ejection fraction would be normal but the LV not able to increase its end-diastolic volume without excess filling pressures promoting pulmonary edema. The second most common etiology of impaired heart functional reserve is chronic LV hypertrophy secondary to hypertension, wherein systemic afterload reduction is the primary treatment. Third, decreased systolic pump function is often seen in sepsis owing to reduced myocardial adrenergic responsiveness. However, this is often under-appreciated because of the usually co-existent peripheral vasodilation. In septic patients, measures aimed primarily to increase mean arterial pressure, such as the use of vasopressors often results in a decrease in cardiac output because the septic heart is not able to handle the increased load. Importantly, this form of systolic dysfunction is reversible once the sepsis state resolves, but may require inotropes during its height to sustain flow under pressure.  Finally both chronic heart failure patients can also get sick and acute myocardial infarction will impair both diastolic and systolic function. Their treatments include reversing coronary ischemia, if present, afterload reduction and a balanced fluid response. A clear and logical approach to all critically ill patients is needed to quickly separate these diverse forms of heart failure from each other as they have markedly different therapies and clinical trajectories. 

1. Pathophysiology of Acute
Heart Failure in the ICU
Michael R. Pinsky, MD, Dr hc
Department of Critical Care Medicine
University of Pittsburgh

2. Bedside Assessment of
Ventricular Pump Function

3. Determinants of Cardiac Pump Function as
Viewed from the Left Ventricle
Preload (Frank-Starling)
Contractility (Anrep)
Afterload
Heart Rate
Synchrony

4. Heart Failure in the ICU is
Condition Specific
• Post-op hearts
• Stunned myocardium
 decreased contractility, decreased lusotropy
• RV dysfunction
• Dyssynchrony
• Sepsis
• VA Decoupling, decreased adrenergic response
• COPD/ARDS
• RV dysfunction
• Anterior chest trauma
• RV contusion

5. Stroke volume increases with end-diastolic volume
Patterson & Starling. J Physiol (London) 48:357-87, 1914
End-diastolic
Volume
Increased
End-diastolic
Volume

6. Cardiac Adaptation to Stress
• Increased preload: Starling Effect
• Decreased unstressed circulating blood
volume
• Increased contractility: Anrep Effect
• Intrinsic increase in calcium flux
• Exogenous catecholamine stimulation

7. Rosenblueth et al. Arch Int Physiol 67: 358, 1959
Starling versus Anrep
Heterometric v. Homeometric autoregulation of the heart
Sudden increase and decrease in venous return
EDV
ESV
Starling
Anrep
Increased Preload
Increased Contractility
Preload
Contractility

8. 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

9. 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

10. LV Pressure-Volume Loop
LV Volume (mL)
LV
Pressure
(mm Hg)
Isometric
Contraction
Diastolic filling
Ejection (stroke volume)
Isometric
Relaxation
End-diastole
End-systole Aortic Valve
Opening
Mitral
Valve
Opening
Patterson & Starling. J Physiol (Lon) 48:465-513,1914

11. Determinants of LV Function
Preload
End-diastolic volume
Afterload
Systolic wall stress
Contractility
Intrinsic myocardial performance
Heart Rate
Chronotropy
Patterson & Starling. J Physiol (Lon) 48:357-79, 1914

12. LV Pressure-Volume Relations
LV Volume (mL)
LV
Pressure
(mm Hg)
Diastolic Filling
V
P
Increased
Stiffness
Diastolic Compliance =
End-diastolic P/V Relation
P/ V
Pinsky Intensive Care Med 29:175-8, 2003

13. Decreased LV diastolic compliance
• Primary LV etiologies
• Ischemia
• LV hypertrophy (hypertension, AS)
• Stunned myocardium post CPB
• Secondary to LV dysfunction
• RV dilation
 Pulmonary hypertension
 Volume overload
• Hyperinflation
• Tamponade

14. Isometric LV Ejection
LV Volume (mL)
LV
Pressure
(mm Hg)
End-
Systolic
Developed
Pressure
CBA
Suga et al. Circ Res 32:314-322, 1973

15. Isometric LV Ejection
LV Volume (mL)
LV
Pressure
(mm Hg)
CBA
End-Systolic Pressure-
Volume Relationship
Suga et al. Circ Res 32:314-322, 1973

16. LV Ejection from a Common EDV
LV Volume (mL)
LV
Pressure
(mm Hg)
A
B
CEnd-Systolic Pressure-
Volume Relationship
Suga et al. Circ Res 32:314-322, 1973

17. Isometric LV Contraction or Ejection
Suga et al. Circ Res 32:314-322, 1973

18. LV Pressure-Volume loops at variable venous return
before and after epinephrine
Suga et al. Circ Res 32:314-322, 1973

19. Effect of Changes in Contractility on the
End-Systolic Pressure-Volume Relationship
LV Volume (mL)
LV
Pressure
(mm Hg)
Decreased Contractility
Increased Contractility
Normal
Failure
Augmented
Suga et al. Circ Res 32:314-322, 1973

20. End-Systolic Pressure Volume Relationship
(generated by IVC occlusion)
Ees
Diastolic compliance
IVC
Occlusion
Ejection

21. Determinants of Afterload
LV Wall Stress
r
P
LaPlace’s Law
Tension = Px r
Maximal tension
at maximal P x r
which usually occurs at the opening
of the aortic value: EDV, diastolic pressure

22. 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

23. Effect of Changes in Heart Rate on Contractility
Force-Frequency Relationship
Liu et al. Circulation 88:1893-906, 1993
70 min-1 70 min-1100 min-1 100 min-1
120 min-1 160 min-1 120 min-1 150 min-1
Chronotropy Diastolic Dysfunction

24. 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

25. LV
Pressure
(mm Hg)
LV volume (mL)
Ees
Effect of Acute Myocardial Ischemia on
Left Ventricular Pressure-Volume Relationship
Ischemia
Ees
Ischemia
Acute LV
Failure

26. Effect of Inotropic Support
following Acute Myocardial Ischemia
LV
Pressure
(mm Hg)
LV volume (mL)
Ees
Dobutamine
Ees

27. Effect of Vasodilator Therapy & Inotropic Support
following Acute Myocardial Ischemia
LV
Pressure
(mm Hg)
LV volume (mL)
Ees
Ees
Decreased
LV ejection
Pressure
Nitroprusside

28. Is Myocardial Contractility Depressed
in Human Septic Shock?
• Used transesophageal echocardiographic measures
of LV volume over time linked to arterial pressure
during brief episodes of nitroprusside-induced
hypotension to generate LV ESPVR
 Gorcsan et al. Anesthesiology 1994, 81:553-562
• Repeated measures following dobutamine infusion
(5 mg/kg/min)
• Repeated measures at 5 days and at recovery (10d)
 Cariou et al. Hopital Cochin, Paris V, 1999-2001

29. Echocardiographic Automated Border
Detection Algorithm Accurately Measures
LV Area
Gorcsan et al. Circulation 1994;89:180-90

30. Gorcsan et al. Circulation 1994;89:180-90
Transesophageal Echocardiography-ABD
and LV Pressure

31. LV Contractile Reserve in Sepsis
0
10
20
30
Day 1 Day 5 Day 9
Baseline
Dobutamine
E’es
*
P < 0.05
n = 10
Depressed
contractility?
Decreased Adrenergic
Responsiveness?
Cariou et al. Intensive Care Med 34: 917-22, 2008

32. Contractility is Depressed in
Human Sepsis
• E’es is depressed relative to paired recovery
values
• Ees increases less in response to dobutamine
during sepsis relative to paired recovery
values
• Myocardial depression persists following
initial recovery from severe sepsis
Cariou et al. Intensive Care Med 34: 917-22, 2008

33. Determinants of Cardiac Pump Function as
Viewed from the Left Ventricle
Preload
Contractility
Afterload
Heart Rate
Synchrony

34. Phase angles in Regional Dyskinesis
a
b
sum
Baseline
Normal Decreased Force Asynchrony
Series Loss Phase loss



35. Model of Regional Dyskinesis
Basal
Ultrasonic
Crystals
Apical
Ultrasonic
Crystals
Conductance
Catheter
Basal
Chordal
Papillary
Apical
Dyskinetic Segment
Strum & Pinsky. A&A 90:252-61, 2000

36. Phase Angles & Regional End-systole
during Esmolol-induced Dyskinesis
R R
ECG
Sum
Basal
Chordal
Papillary
Apical
R R
360
0
Global End-systole
A B C
0
0
-10
0
0
0
45
0
60
0250
0
238
0
200
0
190
0
200
0
0
o
Phase angles (R) Phase angles (Global)Stroke volumes
Asynchronous regions
SVt
Strum & Pinsky. A&A 90:252-61, 2000

37. Two-Point Assessment of
Regional Asynchrony
LV
RV
LBBB Patient
2
-2
cm/s
1.1 sec
Septum
Posterior Wall
Septum
Posterior Wall
Normal Control
2
-2
cm/s
1.5 sec
Dohi et al. Am J Cardiol 96:112-6, 2005

38. Contractile Dyssynchrony
• Most common cardiac dysfunction:
Regional wall motion abnormality
• Degree of dysfunction twice a large as seen
• Increased inotropy can help
– If delayed segments increased contraction rate
• Increase inotropy can hurt
– If only normal segments increased contraction

39. Impaired LV Function
Preload (End-diastolic volume)
Hypovolemia, Diastolic dysfunction
Contractility(Intrinsic myocardial performance)
Ischemia, Septic Cardiomyopathy
Afterload (Systolic wall stress)
Aortic stenosis, Malignant hypertension
Heart Rate (Chronotropy)
Brady and Tachyarrhythmias
Synchrony (coordinated contraction, relaxation)
Regional ischemia, infarction, BBB

40. Acute Heart Failure in the ICU
• Very Common
• Multi-factorial even if resulting in one effect
• Filling pressures can be misleading
• Context specific: MI, ARDS, sepsis, GOK?
• Requires assessment to treat effectively
– Fluids are not always good
– Increased inotropy is not always good

41. Thank You