Heart failure (HF) is the state wherein the heart fails to meet the metabolic demands of the tissues. Therefore cardiac output is insufficient to meet the needs of the tissues. This usually occurs in the face of elevated left ventricular pressures at end diastole.

HF may occur in conditions where the heart is producing a normal cardiac output, but the metabolic needs of the tissues are increased, such as in hyperthyroidism or anemia, and so cardiac output fails to meet their needs. Thus, it may occur in conditions where the strength of the heart muscle appears normal.

However, most conditions that result in heart failure occur as a result of a markedly weakened left ventricle or right ventricle or both.

Congestive heart failure (CHF) occurs when left ventricular pressure at end diastole is elevated.  This results in elevated pulmonary venous pressures and pulmonary edema.

CHF occurs when the volume of blood presented to the heart is in excess of the heart's capacity to move it along. Consequently, fluid builds up behind the heart. If the inability to move the volume of blood forward is due to a left heart problem, then pulmonary venous congestion develops and later pulmonary edema. Subsequently this can lead to pleural effusion and abdominal effusion. If the abnormality lies in the right heart or the pulmonary arteries, wherein they limit the ability to move blood forward, then congestion occurs behind the right heart (causing pleural effusion and/or ascites). 

Many but not all cases of heart failure also have congestive heart failure. Therefore, it is frequently useful to look for evidence of congestion to suggest the presence of heart failure.

Heart murmurs, arrhythmias and other cardiac abnormalities provide evidence for heart disease. Individuals with these signs will not show heart failure until these disease states are severe. Many forms of heart disease may not warrant therapy; however, all forms of heart failure require therapeutic intervention.

Myocardial oxygen consumption (MVO₂) refers to the amount of oxygen consumed (required) by the heart muscle for a contraction.

MVO₂ is increased when:

• HR is increased
• contractility is increased
• ventricular volume is increased (increase in afterload)
• ventricular pressure is increased (increase in afterload)
• ventricular thickness is decreased (an increase in afterload)

MVO2 is decreased when the opposite conditions occur.

The concept afterload is explained later.

Under normal conditions, at rest, myocardial oxygen supply and myocardial oxygen demand are roughly equal. Therefore, there is little to no oxygen reserve for the heart muscle.

Therefore, any situation that increases the myocardial oxygen consumption must also cause an increase in cardiac output and coronary flow (myocardial oxygen supply) or else demand for O₂ will outstrip supply and anaerobic conditions will prevail. This anaerobic state results in less efficient cardiac performance (reduced contractility) and dysrhythmias which can result in a further reduction in cardiac output with further reductions in coronary flow (myocardial O₂ supply). A vicious cycle occurs.

These refer to the general processes, which determine or alter cardiac output.

The determinants of cardiac output are:

1. Preload
2. Afterload
3. Contractility
4. Heart rate
5. Distensibility
6. Synergy of contraction

Preload refers to the stretching of the myocardial cells in a chamber during diastole, prior to the onset of contraction. This is the priming process of the pump. Preload is measured as the end-diastolic volume or end-diastolic pressure.

Therefore, preload is equal to venous return plus the residual volume left in the cardiac chamber after the last contraction.

The Frank-Starling Law of the heart demonstrates the relationship between preload and stroke volume.

Frank Starling Curves

Pressure-Volume Curve

The Frank Starling Curve shows that an increase in preload (end-diastolic volume) increases stroke volume. The Pressure-Volume Curve shows that as volume (preload) increases pressure in that chamber increases. As the pressure in the chamber rises so too does the intravascular pressure (hydrostatic pressure) of the vessels that feed into this chamber. As preload increases and so pressure continues to rise, a point will be reached at which the ventricular end-diastolic pressure is sufficiently elevated to force the intravascular fluid, in the vessels behind that chamber, to weep out into the interstitium that is adjacent to these vessels. If this occurs in the lungs, pulmonary edema results. The vertical line (in the figures) refers to a hypothetical point, such that preload levels to the right of the vertical line promote the extravasation of fluid out of the capillaries into the interstitium (pulmonary edema if we are referring to left ventricular preload). Note also, however, that as preload falls (moving to the left along the curves) the forces that promote pulmonary edema are abolished.

An increase in preload also increases afterload as the volume of the chamber increases (the concept afterload will be discussed later).

The figure on the left shows two left ventricular function curves. Note how an increase in preload causes a marked increase in stroke volume for the normal heart but only a modest increase in stroke volume for the failing left ventricle. Conversely, reductions in preload cause a marked fall in stroke volume for the normal heart but only a modest reduction in stroke volume for the failing heart. Therefore, a marked reduction in preload in the heart failure setting will result in a resolution of pulmonary edema with only a modest reduction in stroke volume (but then these patients can't afford a marked reduction in SV).

As left ventricular preload rises, pulmonary venous distention occurs and then pulmonary edema develops. This may induce elevations in right ventricular preload, which will cause an elevated central venous pressure, jugular venous distention, hepatomegaly and ascites. In addition, pleural effusion may occur. 

a) Excessive left ventricular preload may show 

• pulmonary edema as detected by crackles (if severe) or increased broncho-vesicular sounds (if mild or moderate) on pulmonary auscultation
• hypoxemia/cyanosis
• excessive right ventricular preload

 b) Excessive right ventricular preload may show 

• jugular venous distention or distention of peripheral veins
• positive hepato-jugular reflux test
• pleural effusion as detected by increased/laboured respiration
• hepatomegaly and/or splenomegaly
• ascites (abdominal fluid)
• subcutaneous edema

Afterload refers to the resistance the left ventricle encounters as it tries to eject blood. Afterload is only conceptual and cannot be measured directly. 

Afterload is affected mainly by: 

• ventricular volume (size)
• arterial vasomotor tone (arterial resistance)
• ventricular wall thickness

 Afterload is increased by: 

• increase in ventricular volume
• increase in arterial vasomotor tone
• decrease in ventricular wall thickness

 Afterload is decreased by the opposite changes.

As afterload increases, stroke volume falls and vice versa. However, changes in afterload have a more marked influence on stroke volume in the failing heart vs the normal heart.

An increase in afterload also increases myocardial oxygen consumption. A reduction in afterload has the opposite effect. (link)

The ability to improve cardiac output by reducing afterload represents one of the major advances in cardiovascular therapeutics in the last 25 years.

Afterload cannot be directly measured. However, we can infer that afterload changed if there is evidence that ventricular volume, ventricular wall thickness, or peripheral arterial resistance changed. In most clinical situations we attempt to infer whether afterload is increased or decreased. One can expect that peripheral arterial resistance (and therefore afterload) is elevated in most cases of heart failure (reduced cardiac output) because of 2 facts:

• Blood Pressure = Cardiac Output x Arterial Resistance
• The body attempts to maintain blood pressure by changing arterial resistance (increasing arterial resistance) in heart failure.

Therefore, if we can infer a fall in cardiac output on physical examination, we can expect a rise in arterial resistance and therefore afterload. And so, a fall in cardiac output (and resultant rise in afterload) is inferred by the following possible findings on physical examination: (these all indicate reduced CO)

• cool extremities, fall in rectal temperature
• weakness/syncope
• shock
• slow capillary refill time (>2 sec)
• arrhythmias
• reduced mentation/confusion
• congestive failure signs usually coexist with a reduction in cardiac output

Comment:

Unfortunately, to directly measure a fall in cardiac output usually requires pulmonary artery catheterization, which is not commonly performed in small animals. Therefore, we are continually looking for indirect evidence of a change in cardiac output.

Contractility refers to the inherent strength of the myocardium (ability to shorten). Inotropy is the term used to describe the contractile state of the heart.

An increase in contractility results in:

• an increase in stroke volume (amount of blood ejected from the chamber with each beat).
• a reduction in preload (more complete emptying of the chamber). If pulmonary edema or effusions were present they may resolve with the reduction in preload.
• an increase in myocardial oxygen consumption. Thus, if a perturbation results in an increase in contractility, hopefully cardiac output increases sufficiently to provide for the increased demand for oxygen that the increase in contractility will require.

As contractility falls one can anticipate the opposite effects.

As contractility increases the Frank-Starling function curve shifts upward and to the left. The opposite occurs with a reduction in contractility.

A fall or an increase in contractility can not be detected on physical examination as different from any other cause of a decrease or increase in cardiac output.

The best diagnostic aid to detect a change in contractility is the echocardiogram(cardiac ultrasound examination).

Cardiac Output = HR x Stroke Volume

Chronotropy refers to changes in heart rate.

Increases in HR cause an increase in cardiac output. This becomes self limiting because when HR is excessive cardiac output falls due to: 

• reduced diastolic period which causes:
  • reduced time for ventricular filling (preload)
  • reduced time for coronary perfusion
• increased myocardial oxygen consumption per beat

If a normal heart is forced to beat at 250 bpm, it will be in heart failure in 3-4 weeks and the patient dies in 4-5 weeks. 

If the heart rate is too low, signs of reduced cardiac output will occur.

Distensibility refers to the ease of ventricular filling in diastole (ability to stretch). Lusitropy is the term used to refer to the distensible state of a cardiac chamber.

As a chamber becomes less distensible an equal end-diastolic volume (preload) causes higher chamber pressures. These are transmitted upstream and can lead to pulmonary edema if it is the left ventricle or left atrium that is affected with a reduced distensibility. Thus, for the same amount of preload the less distensible chamber generates very high pressures. Most cardiac disorders tend to reduce distensibility, some very much more than others. Chronic distention of a chamber, particularly the atria, results in an increase in distensibility.

Reduced distensibility of left ventricle or left atrium - may show evidence of left heart congestion: 

• pulmonary edema (crackles or increased broncho-vesicular lung sounds)
• hypoxia/cyanosis
• excessive right ventricular preload

Reduced distensibility of right ventricle or right atrium - may show evidence of right heart congestion: 

• jugular venous distention or peripheral venous distention
• positive hepato-jugular reflux test
• pleural effusion (increased or laboured respiration)
• hepatomegaly and/or splenomegaly
• ascites (abdominal effusion)
• subcutaneous edema

Comments: Note how this looks like elevated preload in the adjacent upstream chamber. In fact, reduced distensibility causes a form of elevated preload in the adjacent upstream chamber.

Synergy of contraction refers to the normal harmonious, coordinated and efficient contractile process involving all chambers of the heart yielding optimal ejection of fluid. The normal left ventricle ejects about 60% of its end-diastolic volume and the normal right ventricle ejects about 50% of its end-diastolic volume.

Abnormalities of synergy of contraction refer to so-called dyssynergy of contraction. Here we are referring to the development of arrhythmias (dysrhythmias). Arrhythmias may result in chaotic, haphazard, non-harmonious contraction of the segments of the heart. In this setting, arrhythmias may markedly reduce stroke volume, in fact to the point of a negligible stroke volume. Most arrhythmias are intermittent and infrequent and so often have no demonstrable effect on cardiac output. Nevertheless, although transient, some arrhythmias can cause syncope (esp. tachyarrhythmias). A 24 hour ECG recording (called Holter recording) can often uncover these intermittent events.

These may be inferred by detecting an irregular cardiac rhythm on auscultation or on femoral arterial palpation. An irregular cardiac rhythm that occurs at a fast heart rate is always due to a pathologic process. An irregular rhythm that occurs at a low normal heart rate may be normal (sinus arrhythmia). Some dysrhythmias occur with a regular cardiac rhythm, thus the absence of an irregular cardiac rhythm does not rule out the possibility of a disorder of synergy of contraction (dysrhythmia). 

Pulse deficits (the absence of a peripheral arterial pulse induced by the heart beat) may be detected if the cardiac rhythm is irregular. Pulses of greatly variable intensity may also be noted. 

The electrocardiogram is the best diagnostic aid to identify and verify these abnormalities. For intermittent arrhythmias, a Holter recording may be required.

The compensatory measures that occur in response to a fall in cardiac output include:

a) Increase in sympathetic tone - resulting in:

• increase in heart rate
  • to maintain cardiac output
• increase in arterial vasomotor tone (increasing peripheral arterial resistance or afterload)
  • to maintain blood pressure
• increase in venomotor tone
  • to increase venous return which increases preload
• release renin from kidney
  • elaborates angiotensin II and aldosterone which increase vasomotor tone (increasing afterload) and increase venous vasomotor tone (increasing preload) and increase Na and water retention (also increases preload)
• increase contractility
• promote arrhythmias
• increase MVO₂ (myocardial oxygen demand)

ACE = angiotensin converting enzyme
ADH = antidiuretic hormone

b) Redistribute cardiac output to coronary and cerebral vascular beds and away from:

• cutaneous vascular beds causing
  • pale mucus membranes
  • slow capillary refill time
  • cool extremities
• splanchnic vascular beds causing
  • impaired intestinal absorption
  • ischemic bowel with ulceration and hemorrhage
• renal vascular beds causing
  • reduced GFR
  • sodium retention and water retention

c) Increased thirst - causing fluid overload (increasing preload).

d) Increased arginine vasopressin (ADH) resulting in:

• increase arterial vasomotor tone (increasing afterload)
• increase fluid retention - fluid overload (increasing preload)

Results:

• Increased afterload --> reduces stroke volume; increases MVO₂.
• Increased preload --> increases stroke volume; increases MVO₂; pulmonary edema.
• Reduced renal perfusion.
• Increase HR --> increase MVO₂; + increase cardiac output.
• Maintain blood pressure for coronary and cerebral perfusion
• Increase contractility --> increased MVO₂; increase stroke volume.
• Promote dysrhythmias --> decrease cardiac output.

Comments: The net effect of these compensatory measures usually has deleterious effects on cardiac performance chronically.

• Increase in neural and hormonal sympathetic nervous system activity.
• Elevation of angiotensin II activity (due to increased renin activity).
• Elevation in arginine vasopressin activity.
• Elevation in endothelin (a hormone released by the vascular endothelium that is a potent vasoconstrictor)

Comment: These factors support arterial blood pressure but increase afterload, which further aggravates the failing heart.

25. List the mechanisms that attempt to promote arterial vasodilation (a decrease systemic vascular resistance) in Heart Failure 

• An increase in arterial vasodilatory prostaglandins.
• An increase in atrial natriuretic peptide.
• An increase in endothelium derived relaxation factor (locally mediated).

Comment: We are only just beginning to recognize the presence of vasodilator mechanisms in the setting of heart failure. Some of these endogenous protective mechanisms become blunted in heart failure thus rendering them relatively ineffective (such as atrial natriuretic factor). In general, the vasodilator mechanisms are overwhelmed by the vasoconstrictor mechanisms in heart failure. This promotes the relentless progression of heart failure.