In heart failure, the cardiac output becomes inadequate as the heart loses its ability to contract and/or relax normally. Most often, the injury is caused by a myocardial infarction (MI). But heart failure can also be caused by other factors, such as myopathies, valve problems, or hypertension.
Heart failure is usually divided into two categories. In systolic heart failure, the problem lies in the ability of the ventricles to contract, whereas in diastolic heart failure, the difficulties arise because the heart does not relax properly.
A typical cause of systolic heart failure is a myocardial infarction. (But various other causes, such as genetic myopathies, alcoholism, valve problems, etc can also be responsible.) In systolic heart failure, damage to the heart muscle tissue causes the ejection fraction (EF) to decrease. Normally, this is about 60-70% at rest. But in heart failure it might fall below 50%, then below 30% or even lower. At 10%, typically the patient will be in life-threatening, cardiogenic shock, featuring hypotension and inadequate perfusion of the tissues. The left ventricle is affected most commonly by an infarction. Failure with the right ventricle, by contrast, is most often caused by preceding failure of the left ventricle.
Because the ventricle is struggling to eject the blood contained within, the ventricle dilates, increasing its end-diastolic volume, which is the volume of the ventricle just before it starts to contract. Normally, of course, the increased end-diastolic volume leads via the Frank-Starling Mechanism to a more powerful contraction and thus an increased stroke volume. But here the ventricle is weak, so that this compensatory mechanism is blunted. Refer to the diagram at right that shows stroke volume as a function of end-diastolic volume for the normal heat. What happens to this relationship in heart failure?
As systolic heart failure progresses, the end-diastolic volume might increase, say, to twice normal. And due to the Law of Laplace this makes matters worse for the struggling ventricle. Observe in the figure how the Law of Laplace relates the pressure in a ventricle to the radius of the ventricle and the tension in the wall of the ventricle. Note especially that the law specifies that a dilated ventricle requires more tension in the wall to generate the same pressure. In other words, the poor, failing ventricle must work harder to accomplish the same thing.
The increased wall tension in the dilated ventricle stimulates growth in the heart. But unlike the adaptive changes that occur normally with training, in the failing heart the hypertrophy is abnormal.
One factor is that the abnormal stress placed on the heart leads to a pattern of protein synthesis in which certain fetal isoforms of some of the contractile proteins are synthesized, and these are not appropriate for the adult heart.
In addition, dilation of the chambers leads to collagen damage, including fibrosis and slipping of the muscle fibers from their usual orientations in the wall.
It is possible also that capillary growth does not keep up with the growth of the muscle fibers, causing difficulties in supplying energy.
Finally, there is abnormal regulation due to continued stimulation of the regulatory systems. Continual sympathetic activation leads to desensitization of adrenergic receptors. Also, angiotensin II is produced at abnormal levels, which leads to increased total peripheral resistance and increased extracellular fluid volume. Both of these factors put additional stress on the heart.
What is the source of angiotensin II? This is actually a good place to discuss this important regulatory molecule which will surface on several occasions this quarter.
The process begins with a precursor protein, angiotensinogen, which is always in the blood. Under conditions associated with poor perfusion of the kidneys, a protein called renin is released from the kidneys. (More on this when we discuss the kidneys.) Renin acts as an enzyme and cleaves from angiotensinogen a peptide of ten amino acids called angiotensin I. But this substance has little activity. However, another enyzme, angiotensin converting enzyme (ACE) acts on angiotensin I and cleaves off two of its amino acids. (This enzyme is found, for example, in the lungs.) The result is angiotensin II, which is one of the most potent regulatory molecules in the body. It causes arterioles to constrict and, by causing the kidneys to retain fluid, increases the extracellular fluid volume.
Why does this sequence get activated in heart failure? Think of it this way: When the kidneys receive poor blood flow, their response is to try and increase the extracellular fluid volume and support the arterial pressure. This response is adaptive when the poor perfusion of the kidneys is caused by hemorrhage or other loses of extracellular fluid. But it is not a solution for heart failure, which is not a significant pathology in nature.
Thus, expanded extracellular fluid volume tends to go hand in hand with heart failure. When this expanded volume leads to pulmonary edema and other symptoms related to the volume overload, heart failure is called congestive heart failure (CHF).
ACE inhibitors are important drugs for treating congestive heart failure (and hypertension too). These reduce angiotensin II levels and thus reduce extracellular fluid volume and dilate arterioles. The latter effect reduces the "afterload" and thus the stress on the heart. (Angiotensin II receptor inhibitors are also available for use in circumstances where the ACE inhibitors have unacceptable side effects.)
Although it may not seem logical at first, beta blockers are now important drugs in heart failure. Indeed, it took quite a while for their use in heart failure to be accepted. Their use makes more sense if you think of them as reducing the strain on a struggling heart (Alternately, they may reduce the abnormal regulation).
More recently, aldosterone antagonists have been found to be helpful. Aldosterone is a steroid hormone especially important for the regulation of the excretion of Na+, which in turn affects extracellular fluid volume. An aldosterone antagonist also had direct positive effects on the heart tissue itself.
(Vasopressin antagonists are a recent development. Vasopressin increases water retention by the kidneys and constricts arterioles. Thus, a vasopression antagonist reduces fluid volume and dilates arterioles.)
Diuretics are used sometimes to reduce the extracellular fluid volume.
Digoxin is also used in heart failure. See the handout for an optional discussion of one of its mechanisms of actions.
Defibrillation and pacemakers may be required if the heart failure leads to arrhythmias, such as ventricular tachycardia.
The ultimate solution to heart failure is to replace the heart through cardiac transplantation.
In diastolic heart failure, the ejection fraction is normal, but the heart does not relax and fill normally because the ventricles become stiff and fibrotic. In other words, their compliance is decreased. A typical cause would be long-standing hypertension. This type of failure is especially common in elderly patients with hypertension. Valve problems can also create similar stress on ventricles.
Hypertrophy occurs here too, but instead of dilation of the chambers, the wall thickness is increased and the end-diastolic volume decreases. Due to these changes, it is difficult for the stroke volume to increase, and the patients have a reduced exercise tolerance.
Abnormal regulation accompanies diastolic heart failure, as it does in systolic heart failure. In both cases, the heart is struggling to pump enough blood. The factors described above under systolic heart failure apply here, including abnormal expansion of extracellular fluid volume.
Overall, the treatments are similar to those used in systolic heart failure.
By contrast with the above hypertrophies, training in an endurance sport leads to a much different hypertrophy of the heart. The pattern of stress placed on the heart in this case leads to increasing wall thickness and chamber expansion. But here the proportions of the heart remain normal, and the abnormal isoforms, abnormal regulation and fibrosis do not occur. Indeed the compliance of the ventricles typically increases with endurance training. The result is a larger, stronger heart with a larger stroke volume. In this type of hypertrophy the structure and function of the heart are normal, and there is no association with heart failure.