HEART FAILURE
INTRODUCTORY COMMENT The primary aim of this chapter is to discuss the pathophysiology of cardiac failure. I do this because of the great confusion about the mechanisms involved, and in the hope that by giving you a simple and rational view of it, you will understand better why different signs and symptoms occur, and so be in a position to best use clinical information in building up clinical diagnoses and treating individual patients.
Some normal values Cardiac output - normally approx. 5 l/min. Stroke volume (SV) - approx. 70 ml. Heart rate - approx. 70 beats per minute End Diastolic Volume (EDV) - approx. 120 ml. Systolic ejection fraction = SV/EDV = approx. 67%. Mean JVP - 0-2 cm. above manubriosternal angle. End diastolic pressure - up to 10 mmHg before "a" wave .br No more than 15 mmHg at "a" wave peak Note: End diastolic pressure (R + L) seem high, but the atria are quite large, so pressure measured is therefore influenced by where the catheter is placed, i.e. on hydrostatic as well as dynamic forces. N.B. Know your "pressure volume loops", and the FrankStarling curves.
DEFINITION This is not as easy as it sounds. An elevated venous pressure may reflect heart failure, but it may also reflect overfilling of the circulation as in over-transfusion, or in sodium and water retention from kidney failure. Therefore, the most generally accepted definition of heart failure is that state when the volume output of the heart fails to keep pace with the metabolic demands of the tissues. You can therefore see that heart failure may occur in absolute terms when the pump itself fails, or when there is a higher demand than it can meet, as in severe thyrotoxicosis.
TYPES OF CARDIAC FAILURE The above definition gives us our first subdivision of heart failure into high output and low output types. The former are relatively rare, but should be remembered, and include such conditions as thyrotoxicosis, high fever, beri-beri heart disease (Vitamin B1 deficiency), anaemia, pregnancy, arteriovenous fistulae and intra-cardiac left to right shunts, Paget's disease of bone, prolonged severe tachycardia of any cause (e.g. supraventricular tachycardia). Actually, the commonest cause of what appears to be a high output failure is now seen when we treat low output failure with vasodilator agents to relieve "pressure overload". In that situation, cardiac output may well be improved back
towards normal, and there is certainly often a marked peripheral dilatation and tachycardia to go along with that. However note that this is not truly a high output state in absolute terms. You will see many classifications of heart failure in the literature, e.g. high- and low- output failure; heart failure related to an elevation of "preload" versus "afterload"; "pressure" versus "volume" overload; "systolic" versus "diastolic" failure; and "backward" and "forward" failure. In Anatomical terms we also talk of right and left heart failure, and in Pathological terms acute, sub-acute, and chronic. In simple terms, the heart consists of a pump with one-way valves, and to work efficiently it must fill normally and not be expected to pump against an unduly high pressure/resistance. Therefore, in general, cardiac failure (L. or R.) can be the end result of: 1. "Volume" overload: a) associated with valvular incompetence (eg. AI or MI causing increased end-diastolic LV volume). b) secondary to decompensation with subsequent salt and water retention (e.g. chronic renal failure). 2. "Pressure" overload: a) outflow valve stenosis (e.g. aortic valve stenosis). b) increased peripheral vascular resistance (as in hypertension). 3. Dysfunction of the myocardium itself: a) "systolic" dysfunction b) "diastolic" dysfunction (see below).
Impairment of Cardiac Function versus Heart Failure We should not regard cardiac failure an all-or-none phenomenon. Certainly, in many conditions complete cardiac failure only occurs as a late complication, and beforehand there are lesser degrees where we should try to diagnose the degree of Functional cardiac impairment. In doing so, initially we may not see any evidence at all at rest but, as with other systems, only when the cardiovascular system is put under load, the most obvious here being exercise.
Prior to the stage of any impairment of cardiac function, there may be no symptoms at all. This is particularly true in valvular stenoses where, for example, there must be approx. 50% narrowing of the aortic valve diameter before there is even a pressure drop across the valve itself, and as much as a 70% narrowing before there is any detectable increased resistance to flow. (Why?) Moreover, with valvular and other abnormalities producing various forms of "pressure" and "volume" overload on the heart, i.e. where there is no primary cardiac muscle dysfunction, the heart can call into play .cu compensatory mechanisms to maintain cardiac output near normal for long periods of time. In this respect, we know that cardiac output can be increased by sympathetically-mediated increases in cardiac muscle contractility, that cardiac dilatation and secondary
increases in stroke volume (Starling's law of the heart) can compensate for the volume overloads associated with AI, MI, etc., and that the pressure overload of AS, PS and hypertension can be compensated, for a time at least, by secondary hypertrophy of the appropriate ventricle. Indeed there are many ways in which the cardiovascular system can help compensate for a falling level of cardiac output at any given level of tissue metabolic demand, and it is only when these compensatory mechanisms fail that overall performance of the heart as a pump will be impaired. Let us therefore now look at the sequence of events, compensatory or otherwise, which occur classically during the course of slowly-developing heart failure. What we must do first is to analyze the consequences of impairment in the "forward" function of the heart, or the progression to what we call "forward" failure. This concept is based on fairly firm grounds as we shall see.
[ "Backward" failure (e.g. elevated JVP and oedema in right heart failure), on the other hand, is in my view really a misnomer. As we might expect, if the heart suddenly stopped pumping totally there would be no reason to expect any damming up of blood behind the heart to increase its "back-pressure", at least in a model tube system, because as soon as the heart stopped pumping there would be no cardiac output, and hence no venous return. Actually, the mean venous pressure does rise immediately after the heart stops, perhaps due to its equalizing to a new (low) value throughout the whole circulation, but even here the maximum mean circulatory pressure is only about 10 mm Hg, and we see levels far higher than this in patients with severe cardiac failure. Part of the explanation of at least chronic "backward failure" lies in understanding the mechanism of "forward" or systemic failure, which can arise from an impairment of the right as well as the left ventricle - after all, the left can again only pump what the right delivers to it. The idea of "backward" failure, though a convenient and simple way of remembering and explaining some aspects of heart failure, is basically incorrect.]
Increased vasopressin release may also contribute to this arteriolar constriction, perhaps endothelin as well.
This maintenance of blood pressure, and with it blood flow to the brain and heart, may mean that there are no symptoms of cardiac dysfunction at all, at least at rest. However, on exercise or when the system is put under other load, arterial blood pressure may not be so well maintained. [This occurs particularly with aortic stenosis (AS), where patients may complain not only of the usual "forward failure" symptoms of lethargy and listlessness with easy fatiguability on exertion, but sometimes faintness and even effort-syncope]. Shortness of breath also occurs on exertion, and we can see this in a simple way as just a reduction of cardiac reserve preventing adequate tissue metabolism, but some patients get unduly short of breath for their degree of "forward" cardiac dysfunction, and we shall come back to possible mechanisms for this in a moment.
So at this stage we have a (compensated) situation of somewhat reduced cardiac output, but maintained systemic blood pressure and perfusion to the vital organs (brain and heart), albeit at the expense of perfusion of the kidneys, skin and splanchnic beds. Initially, the symptoms of "forward" failure may be few, and only brought out during exercise. As the condition progresses, the reduction of afferent arteriolar perfusion pressure by the sympathetically-mediated arteriolar constriction leads to further augmentation of renin release, and one which is more sustained (i.e. at rest); the increased angiotensin II formed as a result tends to raise the general systemic perfusion pressure by producing peripheral arteriolar constriction, and to do so without compromising renal function too much because it has a greater effect to constrict efferent arterioles than afferent ones, thus increasing filtration fraction or glomerular filtration rate relative to renal blood flow. Nonetheless, GFR eventually falls, and this leads to the next phase of compensation, viz. SODIUM AND WATER RETENTION. A number of factors contribute to this, as follows:
Forward Failure: A characteristic of the systemic circulation is that arterial blood pressure is maintained as a balance between cardiac output and peripheral resistance, so if the former falls the latter rises. This rise in resistance is brought about primarily, particularly in the acute state, by a sympathetic nervous discharge which shuts down renal, splanchnic and skin blood flow, to have the effect of maintaining not only blood pressure, but blood flow to those vital organs, the brain and heart. This reduction in (renal) splanchnic and skin blood flow can also be augmented in appropriate circumstances by the release of renin, partly from a direct Beta 1- sympathetic activation, and partly from the local effect of a reduction in blood pressure to the kidney at the level of the afferent arteriole. This released renin enzyme reacts with an alpha 2 globulin substrate in blood to produce angiotensin 1 which, on conversion to angiotensin II in the lung, acts directly on arterioles, (also indirectly by augmenting nor-adrenaline release from vascular sympathetic nerve terminals) so giving a real boost to the vasoconstrictor effect of sympathetic stimulation.
(a) In the RENAL bed, whilst angiotensin helps to maintain filtration fraction, the afferent arteriolar constriction brought about by the direct influence of sympathetic nervous activation will mean that overall glomerular filtration rate (mls/min) will be reduced, leading to sodium retention. The kidneys are also involved in an indirect mechanism to cause sodium retention, namely the stimulation of aldosterone secretion from the adrenal zona glomerulosa by the increased levels of circulating angiotensin II, this aldosterone acting on the kidney at the level of the distal convoluted tubule to enhance sodium reabsorption (in exchange for K+ and/or H+).
(b) In the SPLANCHNIC BED, vasoconstriction will lead to a reduction in liver blood flow, and because this is the site of aldosterone clearance, the latter will be reduced, so promoting further increases in plasma aldosterone, and therefore further sodium retention as heart failure
advances. In a similar way reduced hepatic ADH clearance may contribute to water retention.
You can see therefore, that there are many factors which tend to promote sodium and water retention and cause an increased blood volume when heart function is impaired. (Of course, this sodium chloride will be distributed not just in the blood volume, but across the total extra-cellular fluid compartment - can you work out why?). The increased blood volume will tend to find its way into the high capacitance vessels of the circulation, particularly the veins (the venules often being relatively constricted in heart failure under the influence of the increased sympathetic drive). These will expand to accommodate the blood volume, initially with very little increase in venous pressure. However, as they stretch more towards their elastic limits, the pressure will eventually go up correspondingly, so that the venous pressure will gradually increase.
This increased venous pressure (together with venular constriction) will have two effects. Firstly it will cause a higher "back-pressure" on the capillaries in the systemic circulation tending to produce an increase in the amount of interstitial fluid (i.e. oedema - see next chapter), and secondly lead to an elevation of the central venous pressure (as evidenced for example by an elevated JVP).
It is important to grasp the sequence of cause and effect here, namely .cu primary sodium chloride retention with secondary interstitial oedema and elevation of the jugular venous pressure. i.e. not "backwards" right heart failure with a primary increase in venous back-pressure causing intersitial oedema. We will also see this same principle demonstrated when we come to discuss so-called "backward" failure of the left heart in relation to an elevated pulmonary venous pressure associated with pulmonary congestion and pulmonary oedema.
Effect of Increased Venous Pressure in Heart Failure: If for the moment we take the heart as a single chamber, you can see that the increased venous pressure produced above will lead to cardiac dilatation. Up to a point this will be helpful, because by increasing initial cardiac fibre length, it will increase the force of ventricular contraction on the basis of Starling's law of the heart. Thus, provided dilatation is only moderate, the fluid retention and increase in blood volume will work in a compensatory way to bring cardiac output back now somewhere towards normal. (This is why we don't aim to bring the JVP right back to normal in treating right heart failure). But, beyond a certain point, further sodium retention and cardiac dilatation may become self-defeating because of several factors. Firstly, when dilatation becomes too great, we get on to a plateau of the Starling curve where further dilatation cannot further improve the strength of cardiac contraction, and may worsen it. Cardiac dilatation also brings about a problem due to the law of LaPlace, because more work is required to generate a given force when the heart is dilated (the tension which has to be overcome by the contracting ventricle is directly proportional to both the pressure
within its lumen and lumen .cu diameter). Thirdly, cardiac dilatation may lead to incompetence of the AV valves (mitral and tricuspid). Three factors can be involved in this, depending on circumstances. In some cases, despite their apparent rigidity, the AV valve rings do dilate. In addition, there is often also papillary muscle dysfunction as part of the overall impairment of ventricular contraction. Finally, in ventricular dilatation, the papillary muscles may be skewed so that complete apposition of the valve leaflets is no longer possible. A high venous pressure also means a high left ventricular end - diastolic pressure, and other things being equal, this will impair coronary perfusion (by lessening effective coronary perfusion pressure); and the reduction in coronary blood flow will impair myocardial function still further. These effects of gross sodium and water retention probably help explain the release of vasodilator and natriuretic factors such as a trial natriuretic peptide, prostaglandins, and dopamine in severe heart failure.
Left Heart Impairment/Failure So far, we have accounted for the "forward" aspects of heart failure, but why do we see more pulmonary congestion/oedema and less peripheral oedema in .ul left heart failure, and the contrary in right.
Actually, we see very little detectable oedema at all (and no significant elevation of the JVP) until the very late stages of what we call left heart failure. There are probably two reasons for this. Firstly, if you think of it, most impairment of (the stronger) left heart function is only manifest under load (such as exercise, change in posture etc. - see below) and not at rest until very late. Therefore, any "decompensation" i.e. inability of cardiac output to keep up with metabolic demand, only occurs intermittently, with time in between for circulatory readjustment to return the status quo. Thus, any tendency for "forward" failure to occur (e.g. during exercise) and bring about the reflex changes tending to cause sodium retention will pass off after the exercise period is over. Only late, when compensastory mechanisms fail and left ventricular function is impaired in the basal resting state, will there be any tendency for forward failure to produce .cu continuing sodium retention. Even then, provided the .cu right heart is functioning normally we may see very little .cu peripheral systemic oedema and jugular venous pressure elevation, because even a modest increase in right atrial pressure will be able to increase right ventricular end-diastolic pressure, and hence the output of the normal right ventricle. In this way, we can see how a normally-functioning right heart can limit systemic venous pressure elevation and peripheral oedema. Of course, it can lead to some, so it can at times be difficult to determine whether elevated JVP, oedema, etc. truly reflect L.V. forward failure, or associated right heart failure.
A corollary from the above is important. viz: provided the right heart is functioning normally, any blood volume expansion brought about by L.V. forwardfailure will tend to be pumped by the right heart into the pulmonary circulation. And whilst this may be very effective in limiting systemic venous pressure elevation, etc.
on the right side of the side heart, it carries the consequence of increasing the volume of blood in the lungs. What happens is probably this. As left heart forward-failure begins to persist in the basal state, fluid retention also becomes persistent, and the increased volume of blood, though first tending to be held at low pressure in the systemic venous circulation simply by its size, eventually increases systemic venous pressure and therefore the output of the right heart; and of course the left heart, having had its reserves of function already compromised, cannot increase its output in response to this. The important point to grasp is this: In this situation there is probably a temporary imbalance in the output of the two ventricles, the right being greater than the left, until a new equilibrium is reached. And, such equilibrium will tend to be achieved, because the (moderately-impaired) left ventricle will still have some reserves of compensation, viz some ability to increase its output as increased left atrial and end-diastolic ventricular pressure leads to left ventricular dilatation, and hence to an increase in left ventricular output according to Starling's Law of the heart.
So we can now see why the usual concept of "backward" failure applied to left ventricular failure is probably incorrect. According to old explanations, failure of the left ventricle leads directly to an increase in ventricular enddiastolic pressure, and therefore a "back-pressure" on the pulmonary veins, capillaries etc. But as we have seen, when a heart stops beating, venous return also stops, and mean pulmonary "back pressure" does not rise very much. By the present view, we can see that pulmonary congestion and oedema could arise as a consequence of fluid retention from L.V. forward failure through a normally functioning right ventricle driving the retained fluid into the pulmonary bed.
We are now in a position to explain some of the symptoms of "forward failure" resulting from left rather than right ventricular dysfunction. Firstly, shortness of breath on exertion is a more prominent feature of left heart failure than right (in the latter, exertion produces more in the way of "forward" symptoms of lethargy, fatiguability etc, and fluid is retained in the periphery.) Shortness of breath on exertion is a very early symptom of left heart failure, even before there is much in the way of fluid retention. As I see it, the left ventricle is unable to keep pace in this situation with the increased demand of exercise, so that its output cannot increase appropriately, whereas that of the right heart can. Now, you may say that the right heart can only pump what the left heart supplies it (in the same way as the output of the left heart is determined by the right). But as we shall see clearly with acute heart failure, the sympathetic discharge associated with exercise can cause not only an arteriolar constriction reducing of splanchnic, renal, and skin blood flow, but also a venoconstriction, and with that a reduction of the amount of blood in the venules. And, as discussed, this in turn can increase right atrial pressure, and the normal right heart will respond to this by increasing its output (Starling's Law). So there can indeed be an imbalance between the outputs of the two ventricles during exercise, leading to pulmonary congestion. This may well explain why there is more feeling of dyspnoea on exercise with a given degree of left as opposed to right heart failure, because this increased pulmonary blood volume will increase pulmonary venous pressure and therefore
pulmonary capillary pressure and lung compliance, so that the work of respiration will now be increased.
Orthopnoea and paroxysmal nocturnal dyspnoea (PND) are explicable on a similar basis. These symptoms occur with moderate left heart failure, when there is already an increase in circulating blood volume. This increased volume will be distributed throughout the whole vascular compartment, both systemic and pulmonary, but whilst the patient remains upright the rise in pulmonary venous pressure will be kept to a minimum by the gravitydependent pooling of blood in the legs. However once the patient lies flat, the situation will be rapidly altered, and particularly where the right heart function remains normal, the sequence of events: elevated JVP - elevated atrial pressure - increased right ventricular end diastolic volume increased right heart output, will rapidly shift blood to the pulmonary venous bed and capillaries. Again, by dilating, the left heart will compensate for this, but only at the expense of a much elevated pulmonary venous pressure, causing initial discomfort on lying flat, then shortness of breath, and finally pulmonary oedema.
The foregoing suggested mechanism of pulmonary congestion in left heart failure is important. The message is really that "backward" failure though an easy and convenient way of thinking, is really a consequence of forward failure. Despite this, there may be one sense in which "backward" failure sometimes occurs, particularly in left heart failure where the left ventricular function remains good, as in severe mitral valve stenosis. Here, very high left atrial (and therefore pulmonary venous) pressures can be achieved per se, and in this situation pulmonary arteriolar constriction may be a secondary consequence (? due to pulmonary hypoxia associated with interstitial congestion/oedema). Such pulmonary arteriolar constriction will, in turn, cause pulmonary hypertension, and since the right ventricle is just not built to withstand much pressure overload, it will soon fail. However, this is the unusual, rather than the usual mechanism of what we call "right heart failure" secondary to left heart failure. In my view, by far the commoner explanation of "congestive" (left and right) cardiac failure is that discussed above.
I emphasize that we should talk not of left (or right) ventricular failure, but of degrees of dysfunction. In the same way we should not slip into the trap of using the glib phrase left ventricular failure, unless we know the left ventricle to be the anatomical site of the functional problem; where we do not know, we should talk of left heart or right heart impairment/failure.
Primary Right Heart Impairment/Failure Here, we will again see the evidence of "forward failure", because the left ventricle cannot pump more than the right delivers to it. But, this time, the right ventricle is the one which will not be able to deal with the increase in fluid retention, so that there will be a disproportionate rise in jugular venous pressure, peripheral systemic venous pressure and peripheral oedema, compared with primary left heart failure. As R ventricular function diminishes, the pressure gradient between the right atrium and the left can become the major driving force for pulmonary perfusion. This particularly applies in cases where the interventricular septum is also dysfunctional (as in patients with inferoposterior myocardial infarction; also severe L ventricular failure), where R. heart failure can sometimes be very severe. This is because an important part of normal R. ventricular systolic ejection function is due to the interventricular septum bulging in a piston-like fashion into the R.ventricle. The loss of this mechanism when the septum as well as the R. ventriclar wall is dysfunctional, can result in severe R ventricular failure. One can often do little to help in these circumstances, except to (i) ensure that the pre-load on the R. ventricle (JVP) is not reduced too much (e.g. by overuse of diuretics), and that there is good R. atrial function to help the R.heart driving force, i.e. co-ordinated sinus rhythm. See refs 1-3 for further reading.
Acute (left) Heart Failure In this situation, there is not time for sodium retention, which requires some days, and yet we often see a sudden elevation of left or right venous pressure when the corresponding side of the heart fails. Part of the reason for this is probably related to the sympathetic peripheral .cu veno-constriction which drives blood from a peripheral to a more central location. And, in the situation of left heart failure with maintained normal right heart function, this blood will again be driven from the systemic venous capacitance reservoirs to the left side of the heart as above. Now, we know that the failing left heart is on a different and flatter slope of Starling's curve, so it will not be until the blood volume displaced in this way causes the left ventricular end-diastolic pressure to rise to a considerable degree that improvement in left ventricular contraction will occur (and with it a new balance of the two ventricular outputs); but at such equilibrium the left atrial and pulmonary venous pressure may well exceed the threshold for pulmonary oedema (Starling's law of capillary forces).
There are those who are skeptical about this postulated mechanism of elevated pulmonary pressure in either acute or chronic left heart failure, and argue that when measured there is no detectable difference in the output between the right and left ventricles. However, there are two important points. First, it takes remarkably little disequilibrium between the two ventricles to build up a substantial redistribution of blood with alteration of venous pressures by the mechanisms outlined. Thus, one ml per heart beat extra blood pumped out by the healthy right heart (say, total 70 mls/stroke) in comparison with the left (say, 69 mls/beat or a reduction of about 1.5%) would, other things being equal, add up to 60 mls extra blood delivered to the left heart every minute; and if unlimited over an hour this
would result in an extra 3.6 litres of blood in the lung, with an impossibly gross increase in venous pressure! Thus even this small transient discrepancy, which is probably beyond the detection limit of the most sophisticated current methods for measuring cardiac output, could lead to gross changes. Secondly, because of the increasing left ventricular end-diastolic pressure associated with the above imbalance, the left heart will dilate, and with it stroke volume (Starling's Law) will increase, so that the output of the two ventricles will soon return to equality (long before the above 3.6 litre discrepancy, thankfully!). At that point we would expect no discrepancy in output of the left heart versus the right.
The concept of "systolic" and "diastolic" heart failure This is an increasingly important classification, born of the pressure-volume loops which have proved so useful in studying experimental heart failure. You will hear much about these, but to understand them, you must grasp the point that the curves do not relate pressure or volume changes over time, but pressure/volume changes per se.
Systolic failure is fairly easy to understand. Such failure arises when the cardiac muscle becomes flabby and poorly contractile such as in alcoholic cardiomyopathy. In this model, the initial response is one of cardiac dilatation, which for a time at least can be compensatory (Starling's law of the heart), but eventually failure supervenes as discussed above. Even some of the valvular conditions which produce "volume" overload such as aortic and/or mitral incompetence, produce much the same thing, i.e. dilatation without much in the way of hypertrophy of the cardiac muscle, so that again a flabby myocardium eventually results.
Diastolic failure. Perhaps a more important concept under this heading derives from the term "diastolic" failure. This is particularly important in the left ventricle and arises when the ventricular wall is very stiff, be it due to left ventricular hypertrophy (e.g. in systemic hypertension, aortic valve stenosis), or to myocardial ischaemia/infarction/fibrosis, infiltration of the heart (amyloidosis, haemochromatosis, sarcoidosis), constrictive pericarditis or other "restrictive cardiomyopathies". Here, because of ventricular wall stiffness, diastolic filling is difficult. And since the left ventricle can only pump out what comes in, cardiac output is impaired as a result, despite good systolic contraction. Up to a point, even this form of impaired cardiac function can be compensated, in the first instance by ejecting a greater quantity of end ventricular diastolic blood volume (normal ejection fraction only approx. 70%) and by atrial hypertrophy increasing ventricular filling late in diastole by more forcible atrial contraction. However, as the ventricular wall stiffens further, these compensatory mechanisms will not be able to cope, and heart failure will again eventually supervene; and as you can imagine, this can occur very rapidly if atrial fibrillation suddenly complicates the clinical course at any time.
Rational Treatment of Heart Failure All of the above is important if we are to treat heart failure rationally. Some aspects of treatment are self-evident, e.g. the use of positive inotropic agents, such as digoxin, to increase the strength of cardiac muscle contraction. But as we have seen, many of the changes such as sodium retention and increase in venous pressure are, up to a certain limit, actually quite useful in compensating for the reduction in cardiac output (Starling's Law). The corollary is that we should not attempt to dry a patient out completely and return his blood volume and venous pressure right back to normal (for example with diuretics). This is particularly true in right heart failure, especially acute right heart failure, because the output of the left ventricle is totally dependent on what it receives from the right, and the latter may in turn be highly dependent on the increased right venous filling pressure for its compensated function. Indeed, under some circumstances in this situation, e.g. where patients are dehydrated, plasma volume expansion may be necessary rather than diuretics (together, perhaps, with the administration of positive inotropic agents), to improve systemic arterial blood pressure and flow. And the only price paid for this may be an increase in peripheral oedema.
Diuretics are traditionally used to treat right heart failure, but when we think of the above we should pause to wonder why, especially since the mild associated peripheral (dependent) oedema of right heart failure may not produce much discomfort. On the other hand, pulmonary oedema from left heart failure can be life-threatening, so much so that until recently the powerful diuretics like frusemide were the first line drug treatment of acute left heart failure. We used to give morphine as well (and still do when we are sure there is no C.O.A.D.). This not only helps overcome discomfort, but is also said to be a systemic venodilator, i.e. allows the peripheral venules to accommodate more blood, hence leading to a peripheral redistribution of blood and therefore lessening of left atrial pressure. In the same way, the application of venous tourniquets to the limbs was, and remains, a very useful emergency treatment of left heart failure. More recently, with the IV use of very effective peripheral venodilators such as isosorbide dinitrate or glyceryl trinitrate, it has been shown that left heart failure can be treated very effectively as well by venodilatation, particularly in acute left heart failure where there may be very active peripheral systemic (sympathetic) venoconstriction. In this situation, peripheral venodilatation can very effectively allow the increased pulmonary blood volume to be diverted to a now-higher capacitance peripheral systemic venous circuit. In practice, tradition and empirism still have their influence, so the present (and quite rational) approach is to give both venodilators and (intravenous) diuretics simultaneously (as well as digoxin), particularly in severe LV failure.
We have just seen that where cardiac "pre-load" is high, venodilators can be very effective therapeutically. In the same way, where the primary problem underlying the heart failure is an increased ventricular pressure "afterload" as in systemic hypertension, then systemic arteriolar dilators can be equally effective. These are thought to act mainly by reducing the pressure against which the heart has to pump,
so reducing cardiac work. Such vasodilators may act even more directly in some circumstances, such as in aortic incompetence, where reduction of blood pressure can lessen the actual functional degree of aortic incompetence. Note, however, that in aortic stenosis, peripheral systemic blood pressure after-load (i.e. beyond the narrow aortic valve) is already low, so that agents which reduce "afterload" are not only unnecessary but contra-indicated, since they may cause blood pressure to drop profoundly (as we have seen, this may occur in any case on exercise, or even spontaneously, in this condition), with the consequence of reduced coronary perfusion.
"Afterload" or blood pressure reduction makes good sense in circumstances where the heart failure is secondary to systemic hypertension, but in cardiac impairment from other causes, e.g. primary left ventricular dysfunction, its rationale is not so obvious, especially because at the extreme it will tend to overcome that very peripheral systemic arteriolar constriction we regard as vital for maintaining blood pressure (see above). Traditionally, it is thought that blood pressure reduction in this situation helps by reducing the "pressure work" the heart has to do, so allowing it to do more volume (i.e. cardiac output) work, and this is certainly seen in many circumstances. But if we take this view, what we are saying is that the reflex and compensatory mechanism the body sets in train following a reduction in cardiac output are not necessarily beneficial, at least when carried too far. And perhaps this is to some extent true, because at least in the recumbent posture very little pressure is needed for continued brain perfusion (expecially if cerebral arteriolar resistance is low). But there is another possible (theoretical) mechanism of vasodilator action. We know that the coronary arteries and arterioles are well supplied by sympathetic nerves, and if the sympathetic discharge associated with any heart failure ever spread to cause an increased .cu coronary vascular tone, then we would certainly have gone beyond the realms of ventricular compensation. Because of this, it may be that some of the improvement shown by vasodilators is via a reduction of coronary resistance to give an important increase in coronary blood flow, particularly in situations such as myocardial ischaemia where limitation of coronary artery blood flow may be the major problem underlying the left ventricular dysfunction.
Some of the old arteriolar vasodilators for after-load reduction were not particularly effective. However, the advent of the angiotensin converting enzyme inhibitor drugs such as captopril and enalapril has seen a dramatic change, probably partly because they interfere with an important system (the renin-angiotensin system) which is known to be activated in heart failure and which causes direct vasoconstriction (angiotensin II) as well as an indirect effect to promote sodium retention (and hence increased pre-load) by stimulating aldosterone secretion; but they have other vasodilator mechanisms as well.
Note that where afterload is increased, compensatory hypertrophy may maintain left ventricular function relatively normal for long periods of time. But this, too, has its limits. Firstly, the hypertrophied fibres are not absolutely normal in function, and moreover have a rather precarious
capillary surface area to myocyte volume ratio. Secondly, even with the hypertrophied heart, there comes a time and degree of severity (particularly with a progressive lesion) when it just cannot continue to maintain normal cardiac output, even at rest, so that cardiac failure occurs. This can sometimes be quite dramatic, and many of us wonder why heart failure can be so sudden in such chronic conditions as aortic incompetence or aortic stenosis. The answer probably lies partly in the above, viz, that the heart muscle does reach a stage when it cannot further compensate for the continuing load imposed by the progressive nature of the underlying condition such as aortic stenosis. When any valve outlet becomes very narrow, stenosis may not have to progress much in absolute terms to give a great absolute increase in resistance to flow and therefore demand for cardiac work. Thirdly, remember that the hypertrophied left ventricle is stiff, so causing problems of diastolic filling, ands this can become a particular and rapid problem if atrial fibrillation suddenly supervenes (see above). In the final analysis, though, whether we are dealing primarily with progressive pressure or volume overloads, systolic or diastolic types of ventricular dysfunction, myocardial ischaemia or otherwise, there will come a time when the heart will fail and become grossly dilated - and at that stage high end-diastolic pressures will reduce coronary (diastolic) perfusion to aggravate the situation still further. At that stage, the heart has indeed failed.
Having digested the large meal of the previous three chapters you should now be in a position to solve any clinical problem associated with cardiac or respiratory malfunction.
MULTIPLE CHOICE QUESTIONS A. Mechanisms in Disease: A patient presents with left heart dysfunction secondary to aortic valve incompetence. Which of the following would be characteristic? 1. A wider pulse pressure than usual at any given level of heart failure. 2. A third heart sound. 3. Concentric ventricular hypertrophy. 4. A loud first element to the second heart sound at the base. 5. A raised systemic diastolic blood pressure. 6. A low pulmonary venous pressure. 7. A 10 cm increased jugular venous pressure as an early sign. 8. Systemic arteriolar dilators should be of particular benefit in improving cardiac output. 9. An early diastolic murmur at the left sternal edge. 10. The intensity of the murmur associated with aortic incompetence is a good guide to its severity.
soft (25), and there is only a very narrow split to the second sound on inspiration (26). An added fourth heart sound is heard at the cardiac apex (27). The murmurs heard are as follows: there is a loud, harsh, rough systolic murmur maximal over the base of the heart and conducted to the neck, more to the right than left (28). This murmur clearly begins after the first heart sound, becomes maximal in midsystole (29), and runs through almost up to the first component of the second heart sound (30). On sitting the patient forward there is also a soft early diastolic decrescendo murmur immediately following the first element of the second heart sound (31). Whilst the patient is sitting up, you note on chest examination fine, late inspiratory crepitations at both lung bases (32) as well as mild sacral oedema (33). Examination of the limbs reveals moderate bilateral ankle oedema (34). Temp. 37\uo\dC (35). Investigations: Chest X-ray shows borderline cardiac enlargement with moderate pulmonary venous congestion (36). Blood urea and electrolytes normal (37). Haemoglobin, white cell count and platelets normal (38). Plasma albumin levels normal (39). Plasma creatinine slightly raised, and creatinine clearance at lower limit of normal for age (40). Draw up your columns to solve the problem as previously outlined, before looking at the way I have done so. Only in this way will you grasp the technique. Having drawn up your table in the usual way, you should now be in a position to solve the problem. Any questions will be cast as follows:
Clinical Problem-Solving A 72 year old man (1) presents with increasing shortness of breath on exertion (2) over a period of 12 months (3), a three months history of discomfort and shortness of breath on lying flat (4), and a two week history of awakening at night short of breath (5). He has noticed no palpitation (6) but for about 4 months has had occasional "tight" retrosternal chest pain on severe exertion (7), and on one or two occasions a faintness (dizziness) on exertion as well (8) - indeed on one occasion he "blacked out" completely (9). No cough, sputum or wheeze (10). No shivers or sweats (11). No weight loss or anorexia (12). No other symptoms of relevance in the immediate or long-term background. Married. No stresses. Nonsmoker. Occasional alcohol (13).
WHICH OF THE FOLLOWING IS/ARE CORRECT. 1. This patient shows evidence of impairment of left heart function. 2. The elevated venous pressure and peripheral oedema can be taken to indicate primary impairment of right ventricular function. 3. The added fourth heart sound is due to the cardiac dilatation. 4. The primary cause of this patient's problem is a "pressure" rather than a "volume" overload. 5. The diastolic murmur is classical of mitral valve incompetence.
Examination reveals a relatively old man who looks reasonably fit (14). Abnormalities are confined largely to his cardiovascular system (15). Pulse rate is 72/min and regular (16). The pulse at the wrist has a normal downstroke (17), but the upstroke, assessed at the carotid pulse, is slow and prolonged (18). BP 120/80 mm Hg (18a). The jugular venous pressure is at a height vertically 8 cm above the manubriosternal angle (19), measured with the patient lying at 45 degrees. Both "a" and "v" waves are present (20). Trachea mid-line. Examination of the heart reveals a slowly thrusting apex beat (21) in the fifth left intercostal space 2 cm outside the midclavicular line (22). Auscultation findings are a normal first heart sound at the apex (23), with a soft second heart sound (24); the first component of the second heart sound over the base is very
6. He has evidence of haemodynamically significant aortic stenosis. 7. The thrust over the cardiac apex suggests right ventricular hypertrophy. . 8. The oedema is most likely due to hypoproteinaema. 9. The narrow splitting of the second heart sound is most likely related to a right bundle branch cardiac conduction block. 10. Syncope with exercise is thought to be related to a blood pressure fall on effort in this condition.
11. The length of this particular systolic murmur is of no value in assessing the haemodynamic significance of the underlying valvular lesion. 12. Arteriolar vasodilators would be very useful in treating this particular patient's major haemodynamic problem (NO!). 13. This patient needs valve replacement of the predominantly involved valve.
DIAGNOSTIC DISSERTATION Chronic background condition: 1. This patient has a 12 month history of increasing SOB which subsequent events suggest to be secondary to aortic valve pathology, predominantly stenosis. Though the symptoms are of only 1 year's duration, we know that valvular stenosis can progress silently in clinical terms initially - e.g., up to 70% narrowing before any symptoms so the actual (? degenerative) pathological process could be of very chronic type. 2. Recent (sub-acute) deterioration: No obvious reason for deterioration - no dysrhythmia. Not told about drug history, therefore ? beta blocker (negative inotrope) or sodium retaining (?NSAID for arthritis) added at that time. Further history needed. No evidence of inflammation, no signs of bacterial endocarditis, but do blood culture to exclude this as cause of deterioration. 3. Aortic valve stenosis is haemodynamically significant: a) Angina of effort - ? secondary to decreased (diastolic) BP on exercise causing decreased diastolic coronary perfusion. b) Syncope of effort - ? secondary to marked decreased BP on effort causing inadequate brain perfusion. c) LVH progressing to LVF. d) RHF probably secondary to LVF via increased pulmonary cap. pressure - pulmonary interstitial/alveolar oedema - hypoxaemia - pulmonary arteriolar constriction increased pulmonary arteriolar pressure - RV pressure overload - RHF . 4. Aortic valve incompetence - relatively mild clinically. . Comment: Must have more info. about reason for deterioration over last 3/12. (a) Drug history and more general history (b) Blood cultures to include SBE.
Examiners Comment: Excellent. Mark - 100%!
References. 1. Determinants of hemodynamic compromise with severe right ventricular infarction. JA Goldstein et al. Circulation 88: 359-68, 1990. 2. Importance of left ventricular function and systolic ventricular interaction to right ventricular performance during acute right heart ischaemia. JA Goldstein et al. J. Am. Coll. Cardiol. 19: 704-11, 1992. 3. Current Concepts: Right ventricular infarction. JW Kinch and TJ Ryan. New Engl. J. Med. 330: 1211 -1217, 1994.