Does hemodynamic monitoring complement conventional methods of assessment in the critically ill cardiac patient? DOUGLAS A. HOLDER, * MD, FRcP[c]
conventional methods of patient assessment by the physician at the bedside include analysis of the symptoms and signs presented, counting of pulse and respiratory rates, observation of skin colour and texture, observation of the venous pulse and palpation of the Les methodes cliniques traditionnelles procurent une information qualitative arterial pulse, palpation of the sur Ia fonction ventriculaire gauche du patient gravement malade. Toutefois, non les et par methodes physique de l'examen au cours recueillie percussion of the chest, heart, l'information envahissantes est sujette a d'importantes embOches du fait de sa non specificite measurement of the blood pressure et de Ia variabilite entre les observateurs. L'arrivee de Ia surveillance with a sphygmomanometer, aushemodynamique a mis ces difficultes en lumiere et a permis d'obtenir une cultation of the heart and lungs, information plus quantitative qui est pertinente aussi bien au diagnostic qu'au interpretation of the chest roenttraitement du patient gravement malade. genogram and the electrocardioand analysis of the blood and gram, In recent years there has been con- venous pressure (CVP). However, urine. tinuing improvement in the under- it had many pitfalls and proved standing of the pathophysiologic inadequate in the accurate assessmechanisms of certain disease ment of left ventricular function. Clinical evaluation states, such as shock and pulmo- Ancillary laboratory procedures Because the data obtained in the nary edema. Prior to this the biochemical, hematologic, electroexamination are both subphysical clinician was essentially limited to cardiographic, echocardiographic and qualitative, the more jective rethe findings on inspection, palpa- and radiologic - were used to and quantitative informaobjective they as of problems tion, percussion and auscultation as fine resolution from hemodynamic tion obtained bedside. the at seen were determined by physical examinahas improved the tradimonitoring The parallel development of tion. Up until the late 1960s inof the critically tional assessment vasive hemodynamic monitoring newer therapeutic modalities for This improvement is ill patient. and was restricted by limited technology manipulating preload, afterload responby the temporal highlighted heart and potentially serious complica- the inotropic state of the monitorof hemodynamic siveness easier and safer that it obvious made tions of the methods employed. At in cardiothat time hemodynamic monitoring techniques for invasive hemo- ing to rapid alterations changes such dynamics; vascular of the critically ill patient required dynamic assessment were required by not accompanied often are a sophisticated cardiac catheteriza- not only to identify diagnostic physical in the detectable changes but tion procedure and was therefore problems in the critically ill of limited to major referral centres. also to guide ongoing therapy. The examination. It is the purpose particout to point For example, the myocardial in- eventual development of non- this discussion of confarction research units developed thrombogenic materials incorpor- ular areas where the results inaccurbe may methods ventional in the late 1 960s for the study of ated in devices such as arterial canacute myocardial infarction and the nulas and balloon-tipped flotation ate and even misleading in directIt is complications thereof used such catheters allowed for safe and easy ing diagnosis and treatment. obtained the information techniques as retrograde left ventri- hemodynamic assessment. How- here that monitoring is most invasive from new these with ever, experience the to study cular catheterization the clinical in clarifying useful hemodynamics of myocardial in- monitoring techniques very quickly therapy. and guiding situation that farction. The one physiological brought about the realization In patients with acute myocardial measurement available more gener- hemodynamic monitoring did not conventional methods of infarction but methods traditional replace central ally at the time was the are directed at estimatassessment formed an important adjunct in the of the infarction, the severity ing medicine, *Assistant professor of overall diagnostic and therapeutic for the prelooking particularly director, and ill. University McMaster management of the critically dysfuncleft of ventricular sence coronary care unit, Hamilton primardeal will This discussion General Hospital ily with patients suffering from tion. The results of this type of Reprint requests to: Dr. Douglas A. acute myocardial infarction, al- analysis can give useful informatior. Holder, HGH-McMaster Clinic, though many of the comments can regarding the extent of infarction Hamilton General Hospital, and the prognosis. For example, 237 Barton St., Hamilton, Ont. L8L 2X2 be more generally applied. The
Conventional clinical methods give qualitative information about left ventricular function in the critically ill patient. However, the information gathered from the physical examination and noninvasive methods is subject to important pitfalls with respect to both its nonspecificity and interobserver variability. The advent of hemodynamic monitoring has highlighted these difficulties and provided more quantitative information that is relevant in both diagnosis and treatment of the critically ill patient.
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several prognostic indices were developed in the 1 960s to aid the assessment of prognosis in myocardial infarction.1'2 These indices had limited therapeutic implications but were useful in assessing prognosis. The most useful classification of this population of patients was that described by Killip and Kimball3 in 1968. Their classification of patients suffering acute myocardial infarction is seen in Table I. A more therapeutically useful classification has recently been published4 and will be discussed in detail later. What are the traditional clinical techniques for assessing the ventricular filling pressures and cardiac output (CO) of a patient with acute myocardial infarction? With regard to the filling pressure of the left ventricle, the patient is questioned about exertional dyspea, orthopnea, nocturnal dyspnea and coughing, because, if present, they are clues to an elevation of left ventricular filling pressure (LVFP). Percussion and auscultation of the chest can give evidence of an elevated LVFP or left ventricular failure. In the absence of coexistent pulmonary disease or severe metabolic acidosis, an increased respiratory rate in acute myocardial infarction is often a clue to pulmonary congestion.5 A high LVFP is reflected in increased pulmonary venous pressure, which can cause extrusion of fluid into the pulmonary interstitium and alveoli. This phenomenon may be expressed clinically as pulmonary rales or even pleural effusion. Bilateral fine end-inspiratory rales that are not related to mucus in the airways and hence are unchanged by coughing have been traditionally accepted as representing fluid in the terminal respiratory bronchioles and alveolar sacs.8 High-pitched expiratory sibilant rhonchi may be Table 1-Killip and Kimball's clinical classification of acute myocardial infarction3 Class Clinicalstatus I Noheartfailure II Mild heart failure: rales, S3 gallop, redistribution of blood flow on chest roentgenogram Ill Overt pulmonary edema IV Cardiogenic shock
the only audible adventitious sounds in the patient whose acute interstitial edema has not yet progressed to the point of causing rales.5'7 The presence of coexistent chronic obstructive pulmonary disease or pulmonary fibrosis raises doubts about the meaning of pulmonary rales. Pleural effusion is suspected when dullness to percussion coexists with decreased air entry and diminished vocal fremitus at the level of the effusion, and even a patch of bronchial breath sounds just above the effusion. The right ventricular filling pressure (RVFP) has traditionally been estimated by observation of the jugular venous pulse. Elevation of the jugular venous pressure (JVP) is best appreciated with the patient lying in repose at a 450 angle with tangential light across the neck so that fluctuations of blood in the internal jugular vein can be observed. The height of the column in the jugular vein is measured vertically above the sternal angle, which by convention is taken as being 5 cm above the middle of the right atrium. Another zero reference point is taken as the midway position in the anteroposterior diameter of the chest in the fourth or fifth intercostal space. It should be remembered that the JVP reflects the right atrial pressure and not the left atrial pressure and, therefore, its estimation is a noninvasive method of measuring the CVP. Also, this column of blood and the pressures in the right atrium and great veins are influenced by several variables, including blood volume, right atrial and ventricular compliance and venous tone.8 Occasionally the JVP may be spuriously elevated secondary to venous kinking at the point of thoracic entry, giving the false impression of an elevated CVP. Since the kinking is usually unilateral and most common on the left side, this pitfall can be avoided if one always assesses both sides of the neck and looks for the classic a and v venous waves and normal respiratory variation. The JVP is a valuable clinical sign that should be accurately assessed in all patients, particularly the critically ill. It usually reflects the right atrial pressure and hence
896 CMA JOURNAL/OCTOBER 6, 1979/VOL. 121
the RVFP, and should not be misconstrued as giving useful information about the LVFP; indeed, it may be misleading in certain disease states. In ischemic heart disease, right ventricular infarction, chronic obstructive lung disease and valvular disease on the right side of the heart an elevated JVP is a less reliable indicator of the LVFP. The systemic manifestations of an increased RVFP include not only an elevation of the JVP but also peripheral edema, hepatic enlargement, ascites and even secondary tricuspid regurgitation giving rise to large jugular v-waves and perhaps systolic hepatic expansion. Precordial palpation may add important diagnostic information at the time of physical examination. The presence of a systolic or diastolic thrill raises the suspicion of a significant valvular lesion or shunt. A palpable pericardial friction rub is a clue to underlying pencarditis. The presence of a left parasternal lift raises the possibility of a volume-loaded or pressure-loaded right ventricle with subsequent ventricular hypertrophy. A palpable pulmonary artery and pulmonic component of the second heart sound makes one suspicious of pulmonary hypertension. A palpable first heart sound with a tapping apex beat is classically seen in mitral stenosis. The location of the cardiac apex beat allows one to estimate the cardiac size. A laterally displaced, diffuse, hyperdynamic apex beat raises the possibility of left ventricular volume loading, whereas a sustained apex beat makes one consider a hypertensive left ventricle, as seen in aortic stenosis. The presence of an ectopic impulse over the precordium raises the possibility of ventricular asynergy related to myocardial infarction. In the presence of normal chest architecture an absent precordial impulse is an important finding and should raise the possibility of pericardial effusion or cardiac tamponade, depending on the clinical situation. The laboratory extension of the clinical use of precordial palpation is found in the technique of apex cardiography.9 Auscultation of the heart with
the patient in the supine or left lateral position, with particular attention to diastolic filling sounds, is an important conventional method of clinical assessment that may give useful qualitative information about the LVFP. A fourth heart sound giving rise to a gallop cadence, particularly when associated with a palpable presystolic impulse at the apex, strongly suggests an increased left ventricular end-diastolic pressure (LVRDP).8 However, a fourth heart sound without a coexistent palpable abnormality is present in most patients with acute myocardial infarction and normal sinus rhythm, many of whom do not have clinically serious left ventricular dysfunction. Consequently, as an isolated finding it is an unreliable predictor of the patient's LVFP. The protodiastolic gallop is the pathologic expression of the physiologic third heart sound created by rapid inflow of blood into the left ventricle.10 In the patient with acute infarction its presence implies an increased left ventricular diastolic volume or a significant area of wall motion abnormality or both; hence, it is more useful than the fourth heart sound in indicating serious left ventricular dysfunction. In the presence of tachycardia resulting from increased sympathetic activity, occasioned by a decreased GO, the third heart sound triple rhythm or protodiastolic gallop has been termed the heart's cry ..for help.11 Frequently, because of tachycardia or a prolonged PR interval, the fourth and third heart sounds merge, giving rise to a "summation gallop", which is thought to reflect left ventricular dysfunction. In the absence of left ventricular outflow tract obstruction, hypertension or left bundle branch block, paradoxic splitting of the second heart sound suggests important left ventricular dysfunction.12 It is found in a small proportion of patients, but when present, particularly in association with a third heart sound, it is an important, useful, qualitative sign. These auscultatory phenomena, particularly together with precordial palpation, give the experienced clinician useful, qualitative information about left ventricular function.
An apical systolic murmur in a patient suffering acute myocardial infarction is a rather common finding, being present in about 55% of this population.13'14 The frequency depends on the site of the infarction. However, occasionally the hemodynamic importance of this murmur cannot be readily assessed from the intensity or duration of the murmur in such patients. In particular, loud murmurs may occur in patients with trivial mitral regurgitation, yet there may be no audible murmur in those with significant mitral regurgitation.13 These phenomena depend in part on the vigour of left ventricular contraction, the CO and the amount of valvular regurgitation. Another situation that can occur is the presence of pulsus paradoxus in a hypotensive patient with an elevated JVP whose precordium is unremarkable and whose heart sounds are distant. This should always raise the possibility of cardiac tamponade. To assess the adequacy of the CO clinically one should question the patient about fatigue, malaise and coldness of the extremities. Clues to a low CO from the physical examination include impaired central nervous system function, peripheral cyanosis, decreased skin temperature, tachycardia, lowered systolic blood pressure, narrow pulse pressure and low urine output. Impairment of the sensorium may present as confusion, lack of ability to concentrate, memory loss and so on. The skin temperature can be measured but is usually judged by touch. Peripheral cyanosis may indicate a generally low CO or only regionally decreased blood flow. A decreased stroke volume (SV) may be represented by a decreased systolic blood pressure and reduced pulse pressure. Preservation of an adequate diastolic blood pressure in such an individual implies that the peripheral arterioles have constricted. Significant arterial hypotension is present if the systolic pressure is less than 90 mm Hg or, in a patient previously known to be hypertensive, is at least 40 mm Hg below the lowest pressure previously recorded and is accompanied by compensatory sinus tachycardia. The systemic
blood pressure, as estimated with a sphygmomanometer, is generally an accurate indicator of the intraarterial pressure, but this may not be the case in a critically ill patient. In addition to the variable interpretation of these clinical signs, there is an important observer variation in the ability to elicit them, which provides a further potential error in clinical decision-making.18 Ancillary noninvasive methods Radiologic evaluation Radiologic evaluation of the patient with acute infarction is a noninvasive traditional clinical method that gives a semiquantitative impression of the filling pressure of the left ventricle. Unfortunately, it is the critically ill patient who presents the most difficulty in the obtaining of an adequate radiologic examination, yet it is precisely in such a patient that the information is most useful. It is important in performing chest roentgenography at the bedside with portable equipment to pay attention to details so as to ensure that the roentgenography is done in a reproducible manner for a particular patient. It is desirable to have the patient upright if possible, to avoid misinterpretation of the volume and distribution of pulmonary blood flow as well as to lower the diaphragm as much as possible. This can be accomplished even in the sickest patients and those on respirators by gradually elevating the head of the bed as high as it will go and then placing a large wedge of foam behind the patient to achieve an upright position. Because of the magnification factor it is important to take the films at a standard distance, perpendicular to the x-ray plate; in order to compare serial films the energy used should be constant for a particular patient. The first radiologic change in left ventricular failure usually noted is the redistribution of blood flow to the upper lung zones, with relative prominence of the upper lobe veins. This change is usually followed by the development of fuzzy outlines to the vessels and loss of vessel clarity. Subsequently vessels are noted to be much more
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prominent in the outer lung zones and, finally, frank alveolar edema is manifested by rosette formation in the lung parenchyma. Other clues that there is increased lung water can be discovered by looking at an end-on bronchus and its accompanying pulmonary artery: it may be seen that fluid in the penbronchial interstitium thickens the walls of the bronchus and blurs the margins of its accompanying pulmonary artery. Looking at a lateral chest roentgenogram is often a good way to appreciate whether the outer zone vessels are more prominent than they should be. However, such roentgenograms are difficult to obtain in the critically ill patient. Attention should be paid to the normally clear retrosternal air space, where a general haziness may be noted and vessels may be more prominent. Kerley's B lines, which are thought to be due to thickening of the interlobular septa with interstitial fluid, are important if seen in the costophrenic angles. These, then, are the several radiologic changes that should be sought and are important clues to an increased pulmonary venous pressure. The chest roentgenogram can give other important diagnostic information. As left heart failure becomes more advanced, pleural effusions may occur that, if small, are more likely to be found radiologically than clinically. If the heart is globular or the cardiac silhouette is increasing with time, pericardial effusion is possible. An abnormal configuration of the left heart border, such as squaring-off or bulging, may raise the suspicion of ventricular aneurysm. A widening mediastinum or widening of the aortic shadow with abnormal separation due to medial calcification raises the question of dissection of the aorta. Obvious changes compatible with chronic obstructive pulmonary disease may make the interpretation of pulmonary rales much less specific. Electrocardiographic evaluation
Traditionally the electrocardiogram (ECG) has been used to identify certain dysrhythmic and pathophysiological abnormalities of the myocardium and conduction
tissue. Various rhythm disturbances, such as complete heart block and atrial arrhythmias, may be detected by physical examination, and flutter waves or giant cannon a-waves in the jugular veins, or variability of the first heart sound can occur. Electrocardiographic criteria are available for right and left atrial and ventricular hypertrophy. Persistence of ST-segment elevation following myocardial infarction is a clue to the presence of a ventricular aneurysm. The phenomena of a low-voltage QRS wave and electrical alternans may be associated with severe ventricular dysfunction and pencardial effusion with tamponade. Extensive pulmonary embolism can cause an electrocardiographic pattern of right ventricular strain, right bundle branch block and numerous supraventricular arrhythmias. More recently the ECG has been used to predict certain hemodynamic abnormalities. Heikkilii, Hugenholtz and Tabakin" have reported that the LVFP can be estimated from the P-wave terminal force (left atrial component) of the ECG. They analysed 40 acutely ill cardiac patients both hemodynamically and electrocardiographically, and found a significant inverse correlation between the Pwave terminal force in lead V1 and the mean LVFP, particularly in patients with acute left heart failure. Thus, the ECG can give useful information about the underlying pathophysiology. Its careful interpretation can confirm suspicions raised by physical examination and is occasionally the first indication of underlying disease. Other techniques
It is beyond the scope of this paper to discuss these techniques in detail. Only certain useful areas of application in the critically ill patient will be mentioned. Echocardiography has proved useful in differentiating ventricular dilatation and pericardial effusion. The flail posterior leaflet seen in papillary muscle rupture following acute myocardial infarction may be identified as the cause of mitral regurgitation or a murmur. The detection of wall motion abnormalities, aneurysm and wall thickness,
898 CMA JOURNAL/OCTOBER 6, 1979/VOL. 121
and the prediction of hemodynamic abnormalities may prove useful with future development of the echocardiogram. Nuclear medicine techniques and computerized axial tomography are finding greater application in areas of patient assessment that heretofore required invasive diagnostic procedures. Hemodynamic evaluation
How has more sophisticated hemodynamic monitoring improved the clinical ability to assess cardiac function in the patient with acute myocardial infarction? Earlier hemodynamic assessment of the patient with infarction was attempted with the use of a CVP line, and identification of cardiac failure was based in part on the degree of elevation of the CVP. However, Forrester and colleagues18 studied 50 patients with simultaneous CVP and mean pulmonary capillary wedge pressure (PCW) measurement and found a poor correlation between the two values. Their study revealed not only a poor correlation when these pressures were initially measured, but also that these pressures could respond in a directionally different fashion to the same hemodynamic alteration. This should not be surprising since coronary artery disease is segmental and involves primarily the left ventricle. In health the right ventricle is a much more compliant chamber and so can accommodate a larger volume with a smaller rise in pressure. Since acute myocardial infarction involves the left ventricle primarily, marked changes in the LVEDP do not necessarily cause concomitant changes in the right ventricular end-diastolic pressure (RVEDP). Forrester and colleagues also evaluated the ability of the PCW to predict radiologic pulmonary congestion. They found that patients who had an elevated PCW had an abnormal chest roentgenogram, whereas those who had pressures less than approximately 18 mm Hg frequently had normal chest roentgenograms. The CVP, however, was of no help in predicting radiologic change, nor did it reflect volume shifts as a result of either volume infusion or diuresis. McHugh and associates19 com-
Table Il-Forrester, Diamond and Swan's clinical and hemodynamic classification of acute myocardial infarction23* Clinical status Class I
II Ill IV
Hypoperfusion -
Pulmonary congestion -
Hemodynamicstatust PCW . 18 mm Hg Cl . 2.2 1/mm -
+ + + + + + = present; - = absent. tPCW = mean pulmonary capillary wedge pressure; Cl = cardiac index.
-
+ +
prognostic insights but also practical therapeutic information. For example, the class III patient may be challenged with a volume load to raise the PCW, whereas the class IV patient may require a catecholamine or a vasodilator for a lowering of the PCW and an increase in the CI. The authors also looked at their ability to predict accurately the hemodynamic subset from the clinical criteria and found that their success depended on the particular class of patients under consideration. For example, those in class I, who would be judged to be free of pulmonary congestion and to have a normal cardiac index, were correctly classified clinically two thirds of the time; however, one third of these patients, when assessed with hemodynamic monitoring, actually belonged in a more advanced class of left ventricular dysfunction and were almost equally divided between class II and class III. In class II there was a 50% rate of error in clinical classification, with most of the misclassified patients belonging to class IV by hemodynamic criteria. This was even more significant when it was appreciated that all of the deaths in this group of patients occurred in those of hemodynamic class IV. Class III patients were usually correctly classified clinically except that the presence of hypoperfusion was underestimated. The sickest patients, those with class IV dysfunction, had parallel hemodynamic and clinical changes approximately 80% of the time. Here clinical errors were evenly divided between an underestimate of the PCW and an overestimate of the CI. These investigators have seriously applied themselves to the study of left ventricular dysfunction in acute infarction and have contributed tremendously to our understanding of the problem. Their findings are both illuminating and sobering since even they have a significant error in the clinical estimation of the severity of left ventricular dysfunction in acute myocardial infarction.
Conclusion In the critically ill patient clinical assessment can be likened to a pho-
tograph that is out of focus. It is usually sufficiently clear to allow one to see the nature of the subject. However, as in photography, where the use of the appropriate lens clarifies the picture, so in the critically ill patient hemodynamic monitoring adds considerable clarity to a difficult management problem. This paper has attempted to point out the qualitative nature of many symptoms and signs and the problems in their interpretation. The acquisition of hemodynamic data "on line" in the management of the critically ill patient does not obviate the need for clinical assessment but rather allows diagnosis and therapy to be more refined and quantitative. The present indications for hemodynamic monitoring in this patient population are outlined elsewhere in this symposium. References 1. SCHEIDT S, ASCHEIM R, KILLu' T
III: Shock after acute myocardial infarction. A clinical and hemodynamic profile. Am J Cardiol 26: 556, 1970 2. NoRRIs RM, BRANDT PWT, CAUGHEY DG, et al: A new coronary prognostic index. Lancet 1: 274, 1969 3. KiLuI' T, KIMBALL JT: A survey of the coronary care unit: concept and results. Prog Cardiovasc Dis 11: 45, 1968 4. FORRESTER JS, DIAMOND G, CHAT-
TERJEE K, et al: Medical therapy of acute myocardial infarction by application of hemodynamic subsets (two parts). N Engi J Med 295: 1356, 1404; 1976 5. SJOGREN A: Left heart failure in acute myocardial infarction. A clinical, haemodynamic and therapeutic study. Acta Med Scand suppi 510: 1970 6. MAJOR RH, DELP MH: Physical
7. 8.
9.
10. 11. 12.
Diagnosis, 6th ed, Saunders, Philadelphia, 1962, pp 162-63 FoRGAcs P: Crackles and wheezes. Lancet 2: 203, 1967 BURCH GE, RAY CT: Mechanism of hepatojugular reflux test in congestive heart failure. Am Heart I 48: 373, 1954 TAVEL ME: Clinical Phonocardicgraphy and External Pulse Recording, 2nd ed, Year Bk Med, Chicago, 1972, pp 186-203 BRAUNWELL C: Gallop rhythm. Q I Med 4: 149, 1935 MAJOR RH, DELP MN: Physical Diagnosis, 6th ed, op cit, p 187 SEGMOUR J, BUCHER H: Reversed splitting of second heart sound in ischaemic heart disease. Br Heart I 27: 952, 1965
13. BURCH
GE,
DE
PASQUALE
NP,
PHILLIPS JH: Clinical manifestations of papillary muscle dysfunction.
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Arch intern Med 112: 112, 1963 14. HEIKKILA J: Mitral incompetence complicating acute myocardial infarction. Br Heart J 29: 162, 1967 15. FORRESTER JS, DIAMOND G, FREED-
MAN S, et al: Silent mitral insufficiency in acute myocardial infarction. Circulation 44: 877, 1971 16. KORAN LM: The reliability of clinical methods, data and judgments (two parts). N Engi J Med 293: 642, 695; 1975 17. HEIKKILA
J,
HUGENHOLTZ
PG,
TABAKIN BS: Prediction of left heart filling pressure and its sequential change in acute myocardial infarction from the terminal force of the P wave. Br Heart J 35: 142, 1973 18. FORRESTER iS,
DIAMOND
G,
Mc-
HUGH TJ, et al: Filling pressures in the right and left sides of the heart in acute myocardial infarction. A reappraisal of central-venous-pressure monitoring. N Engi J Med 285: 190, 1971 19. MCHUGH TJ, FORRESTER iS, ADLER
L, et al: Pulmonary vascular congestion in acute myocardial infarction: hemodynamic and radiologic correlations. Ann intern Med 76: 29, 1972 20. DA Luz PL, SHUBIN H, WElL MH, et al: Pulmonary edema related to changes in colloid osmotic pulmonary artery wedge pressure in patients after acute myocardial infarction. Circulation 51: 350, 1975 21. CoHN JN: Blood pressure measurement in shock. Mechanism of inaccuracy in auscultatory and palpatory methods. JAMA 199: 972, 1967 22. RODBARD S: The significance of the intermediate Korotkoff sounds. Circulation 8: 600, 1953 23. FORRESTER iS, DIAMOND GA, SWAN
HJC: Correlative classification of clinical and hemodynamic function after acute myocardial infarction. Am J Cardiol 39: 137, 1977
I BOOKS continued from page 876 BIOLOGICAL IN DEVELOPMENTS STANDARDIZATION. Vol. 42. Proceeding of the Second General Meeting of European Society of Animal Cell Technology. Held at Maison des polytechniciens, Paris, France, 23-26 May 1978. Edited by the International Association of Biological Standardization. Acting Editors: R.H. Regamey, R. Spier and F. Horodniceanu. 210 pp. lIlust. S. Karger AG, Basel, 1979. $36, paperbound. ISBN 3-8055-2989-9 DIFFERENTIAL DIAGNOSIS. The Interpretation of Clinical Evidence. 3rd ed. A. McGehee Harvey, James Bordley, Ill and Jeremiah A. Barondess. 783 pp. W.B. Saunders Company, Philadelphia; W.B. Saunders Company Canada, Ltd., Toronto, 1979. $34.20. ISBN 0-72164562-3
continued on page 936
conventional methods of patient assessment by the physician at the bedside include analysis of the symptoms and signs presented, counting of pulse and respiratory rates, observation of skin colour and texture, observation of the venous pulse and palpation of the Les methodes cliniques traditionnelles procurent une information qualitative arterial pulse, palpation of the sur Ia fonction ventriculaire gauche du patient gravement malade. Toutefois, non les et par methodes physique de l'examen au cours recueillie percussion of the chest, heart, l'information envahissantes est sujette a d'importantes embOches du fait de sa non specificite measurement of the blood pressure et de Ia variabilite entre les observateurs. L'arrivee de Ia surveillance with a sphygmomanometer, aushemodynamique a mis ces difficultes en lumiere et a permis d'obtenir une cultation of the heart and lungs, information plus quantitative qui est pertinente aussi bien au diagnostic qu'au interpretation of the chest roenttraitement du patient gravement malade. genogram and the electrocardioand analysis of the blood and gram, In recent years there has been con- venous pressure (CVP). However, urine. tinuing improvement in the under- it had many pitfalls and proved standing of the pathophysiologic inadequate in the accurate assessmechanisms of certain disease ment of left ventricular function. Clinical evaluation states, such as shock and pulmo- Ancillary laboratory procedures Because the data obtained in the nary edema. Prior to this the biochemical, hematologic, electroexamination are both subphysical clinician was essentially limited to cardiographic, echocardiographic and qualitative, the more jective rethe findings on inspection, palpa- and radiologic - were used to and quantitative informaobjective they as of problems tion, percussion and auscultation as fine resolution from hemodynamic tion obtained bedside. the at seen were determined by physical examinahas improved the tradimonitoring The parallel development of tion. Up until the late 1960s inof the critically tional assessment vasive hemodynamic monitoring newer therapeutic modalities for This improvement is ill patient. and was restricted by limited technology manipulating preload, afterload responby the temporal highlighted heart and potentially serious complica- the inotropic state of the monitorof hemodynamic siveness easier and safer that it obvious made tions of the methods employed. At in cardiothat time hemodynamic monitoring techniques for invasive hemo- ing to rapid alterations changes such dynamics; vascular of the critically ill patient required dynamic assessment were required by not accompanied often are a sophisticated cardiac catheteriza- not only to identify diagnostic physical in the detectable changes but tion procedure and was therefore problems in the critically ill of limited to major referral centres. also to guide ongoing therapy. The examination. It is the purpose particout to point For example, the myocardial in- eventual development of non- this discussion of confarction research units developed thrombogenic materials incorpor- ular areas where the results inaccurbe may methods ventional in the late 1 960s for the study of ated in devices such as arterial canacute myocardial infarction and the nulas and balloon-tipped flotation ate and even misleading in directIt is complications thereof used such catheters allowed for safe and easy ing diagnosis and treatment. obtained the information techniques as retrograde left ventri- hemodynamic assessment. How- here that monitoring is most invasive from new these with ever, experience the to study cular catheterization the clinical in clarifying useful hemodynamics of myocardial in- monitoring techniques very quickly therapy. and guiding situation that farction. The one physiological brought about the realization In patients with acute myocardial measurement available more gener- hemodynamic monitoring did not conventional methods of infarction but methods traditional replace central ally at the time was the are directed at estimatassessment formed an important adjunct in the of the infarction, the severity ing medicine, *Assistant professor of overall diagnostic and therapeutic for the prelooking particularly director, and ill. University McMaster management of the critically dysfuncleft of ventricular sence coronary care unit, Hamilton primardeal will This discussion General Hospital ily with patients suffering from tion. The results of this type of Reprint requests to: Dr. Douglas A. acute myocardial infarction, al- analysis can give useful informatior. Holder, HGH-McMaster Clinic, though many of the comments can regarding the extent of infarction Hamilton General Hospital, and the prognosis. For example, 237 Barton St., Hamilton, Ont. L8L 2X2 be more generally applied. The
Conventional clinical methods give qualitative information about left ventricular function in the critically ill patient. However, the information gathered from the physical examination and noninvasive methods is subject to important pitfalls with respect to both its nonspecificity and interobserver variability. The advent of hemodynamic monitoring has highlighted these difficulties and provided more quantitative information that is relevant in both diagnosis and treatment of the critically ill patient.
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several prognostic indices were developed in the 1 960s to aid the assessment of prognosis in myocardial infarction.1'2 These indices had limited therapeutic implications but were useful in assessing prognosis. The most useful classification of this population of patients was that described by Killip and Kimball3 in 1968. Their classification of patients suffering acute myocardial infarction is seen in Table I. A more therapeutically useful classification has recently been published4 and will be discussed in detail later. What are the traditional clinical techniques for assessing the ventricular filling pressures and cardiac output (CO) of a patient with acute myocardial infarction? With regard to the filling pressure of the left ventricle, the patient is questioned about exertional dyspea, orthopnea, nocturnal dyspnea and coughing, because, if present, they are clues to an elevation of left ventricular filling pressure (LVFP). Percussion and auscultation of the chest can give evidence of an elevated LVFP or left ventricular failure. In the absence of coexistent pulmonary disease or severe metabolic acidosis, an increased respiratory rate in acute myocardial infarction is often a clue to pulmonary congestion.5 A high LVFP is reflected in increased pulmonary venous pressure, which can cause extrusion of fluid into the pulmonary interstitium and alveoli. This phenomenon may be expressed clinically as pulmonary rales or even pleural effusion. Bilateral fine end-inspiratory rales that are not related to mucus in the airways and hence are unchanged by coughing have been traditionally accepted as representing fluid in the terminal respiratory bronchioles and alveolar sacs.8 High-pitched expiratory sibilant rhonchi may be Table 1-Killip and Kimball's clinical classification of acute myocardial infarction3 Class Clinicalstatus I Noheartfailure II Mild heart failure: rales, S3 gallop, redistribution of blood flow on chest roentgenogram Ill Overt pulmonary edema IV Cardiogenic shock
the only audible adventitious sounds in the patient whose acute interstitial edema has not yet progressed to the point of causing rales.5'7 The presence of coexistent chronic obstructive pulmonary disease or pulmonary fibrosis raises doubts about the meaning of pulmonary rales. Pleural effusion is suspected when dullness to percussion coexists with decreased air entry and diminished vocal fremitus at the level of the effusion, and even a patch of bronchial breath sounds just above the effusion. The right ventricular filling pressure (RVFP) has traditionally been estimated by observation of the jugular venous pulse. Elevation of the jugular venous pressure (JVP) is best appreciated with the patient lying in repose at a 450 angle with tangential light across the neck so that fluctuations of blood in the internal jugular vein can be observed. The height of the column in the jugular vein is measured vertically above the sternal angle, which by convention is taken as being 5 cm above the middle of the right atrium. Another zero reference point is taken as the midway position in the anteroposterior diameter of the chest in the fourth or fifth intercostal space. It should be remembered that the JVP reflects the right atrial pressure and not the left atrial pressure and, therefore, its estimation is a noninvasive method of measuring the CVP. Also, this column of blood and the pressures in the right atrium and great veins are influenced by several variables, including blood volume, right atrial and ventricular compliance and venous tone.8 Occasionally the JVP may be spuriously elevated secondary to venous kinking at the point of thoracic entry, giving the false impression of an elevated CVP. Since the kinking is usually unilateral and most common on the left side, this pitfall can be avoided if one always assesses both sides of the neck and looks for the classic a and v venous waves and normal respiratory variation. The JVP is a valuable clinical sign that should be accurately assessed in all patients, particularly the critically ill. It usually reflects the right atrial pressure and hence
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the RVFP, and should not be misconstrued as giving useful information about the LVFP; indeed, it may be misleading in certain disease states. In ischemic heart disease, right ventricular infarction, chronic obstructive lung disease and valvular disease on the right side of the heart an elevated JVP is a less reliable indicator of the LVFP. The systemic manifestations of an increased RVFP include not only an elevation of the JVP but also peripheral edema, hepatic enlargement, ascites and even secondary tricuspid regurgitation giving rise to large jugular v-waves and perhaps systolic hepatic expansion. Precordial palpation may add important diagnostic information at the time of physical examination. The presence of a systolic or diastolic thrill raises the suspicion of a significant valvular lesion or shunt. A palpable pericardial friction rub is a clue to underlying pencarditis. The presence of a left parasternal lift raises the possibility of a volume-loaded or pressure-loaded right ventricle with subsequent ventricular hypertrophy. A palpable pulmonary artery and pulmonic component of the second heart sound makes one suspicious of pulmonary hypertension. A palpable first heart sound with a tapping apex beat is classically seen in mitral stenosis. The location of the cardiac apex beat allows one to estimate the cardiac size. A laterally displaced, diffuse, hyperdynamic apex beat raises the possibility of left ventricular volume loading, whereas a sustained apex beat makes one consider a hypertensive left ventricle, as seen in aortic stenosis. The presence of an ectopic impulse over the precordium raises the possibility of ventricular asynergy related to myocardial infarction. In the presence of normal chest architecture an absent precordial impulse is an important finding and should raise the possibility of pericardial effusion or cardiac tamponade, depending on the clinical situation. The laboratory extension of the clinical use of precordial palpation is found in the technique of apex cardiography.9 Auscultation of the heart with
the patient in the supine or left lateral position, with particular attention to diastolic filling sounds, is an important conventional method of clinical assessment that may give useful qualitative information about the LVFP. A fourth heart sound giving rise to a gallop cadence, particularly when associated with a palpable presystolic impulse at the apex, strongly suggests an increased left ventricular end-diastolic pressure (LVRDP).8 However, a fourth heart sound without a coexistent palpable abnormality is present in most patients with acute myocardial infarction and normal sinus rhythm, many of whom do not have clinically serious left ventricular dysfunction. Consequently, as an isolated finding it is an unreliable predictor of the patient's LVFP. The protodiastolic gallop is the pathologic expression of the physiologic third heart sound created by rapid inflow of blood into the left ventricle.10 In the patient with acute infarction its presence implies an increased left ventricular diastolic volume or a significant area of wall motion abnormality or both; hence, it is more useful than the fourth heart sound in indicating serious left ventricular dysfunction. In the presence of tachycardia resulting from increased sympathetic activity, occasioned by a decreased GO, the third heart sound triple rhythm or protodiastolic gallop has been termed the heart's cry ..for help.11 Frequently, because of tachycardia or a prolonged PR interval, the fourth and third heart sounds merge, giving rise to a "summation gallop", which is thought to reflect left ventricular dysfunction. In the absence of left ventricular outflow tract obstruction, hypertension or left bundle branch block, paradoxic splitting of the second heart sound suggests important left ventricular dysfunction.12 It is found in a small proportion of patients, but when present, particularly in association with a third heart sound, it is an important, useful, qualitative sign. These auscultatory phenomena, particularly together with precordial palpation, give the experienced clinician useful, qualitative information about left ventricular function.
An apical systolic murmur in a patient suffering acute myocardial infarction is a rather common finding, being present in about 55% of this population.13'14 The frequency depends on the site of the infarction. However, occasionally the hemodynamic importance of this murmur cannot be readily assessed from the intensity or duration of the murmur in such patients. In particular, loud murmurs may occur in patients with trivial mitral regurgitation, yet there may be no audible murmur in those with significant mitral regurgitation.13 These phenomena depend in part on the vigour of left ventricular contraction, the CO and the amount of valvular regurgitation. Another situation that can occur is the presence of pulsus paradoxus in a hypotensive patient with an elevated JVP whose precordium is unremarkable and whose heart sounds are distant. This should always raise the possibility of cardiac tamponade. To assess the adequacy of the CO clinically one should question the patient about fatigue, malaise and coldness of the extremities. Clues to a low CO from the physical examination include impaired central nervous system function, peripheral cyanosis, decreased skin temperature, tachycardia, lowered systolic blood pressure, narrow pulse pressure and low urine output. Impairment of the sensorium may present as confusion, lack of ability to concentrate, memory loss and so on. The skin temperature can be measured but is usually judged by touch. Peripheral cyanosis may indicate a generally low CO or only regionally decreased blood flow. A decreased stroke volume (SV) may be represented by a decreased systolic blood pressure and reduced pulse pressure. Preservation of an adequate diastolic blood pressure in such an individual implies that the peripheral arterioles have constricted. Significant arterial hypotension is present if the systolic pressure is less than 90 mm Hg or, in a patient previously known to be hypertensive, is at least 40 mm Hg below the lowest pressure previously recorded and is accompanied by compensatory sinus tachycardia. The systemic
blood pressure, as estimated with a sphygmomanometer, is generally an accurate indicator of the intraarterial pressure, but this may not be the case in a critically ill patient. In addition to the variable interpretation of these clinical signs, there is an important observer variation in the ability to elicit them, which provides a further potential error in clinical decision-making.18 Ancillary noninvasive methods Radiologic evaluation Radiologic evaluation of the patient with acute infarction is a noninvasive traditional clinical method that gives a semiquantitative impression of the filling pressure of the left ventricle. Unfortunately, it is the critically ill patient who presents the most difficulty in the obtaining of an adequate radiologic examination, yet it is precisely in such a patient that the information is most useful. It is important in performing chest roentgenography at the bedside with portable equipment to pay attention to details so as to ensure that the roentgenography is done in a reproducible manner for a particular patient. It is desirable to have the patient upright if possible, to avoid misinterpretation of the volume and distribution of pulmonary blood flow as well as to lower the diaphragm as much as possible. This can be accomplished even in the sickest patients and those on respirators by gradually elevating the head of the bed as high as it will go and then placing a large wedge of foam behind the patient to achieve an upright position. Because of the magnification factor it is important to take the films at a standard distance, perpendicular to the x-ray plate; in order to compare serial films the energy used should be constant for a particular patient. The first radiologic change in left ventricular failure usually noted is the redistribution of blood flow to the upper lung zones, with relative prominence of the upper lobe veins. This change is usually followed by the development of fuzzy outlines to the vessels and loss of vessel clarity. Subsequently vessels are noted to be much more
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prominent in the outer lung zones and, finally, frank alveolar edema is manifested by rosette formation in the lung parenchyma. Other clues that there is increased lung water can be discovered by looking at an end-on bronchus and its accompanying pulmonary artery: it may be seen that fluid in the penbronchial interstitium thickens the walls of the bronchus and blurs the margins of its accompanying pulmonary artery. Looking at a lateral chest roentgenogram is often a good way to appreciate whether the outer zone vessels are more prominent than they should be. However, such roentgenograms are difficult to obtain in the critically ill patient. Attention should be paid to the normally clear retrosternal air space, where a general haziness may be noted and vessels may be more prominent. Kerley's B lines, which are thought to be due to thickening of the interlobular septa with interstitial fluid, are important if seen in the costophrenic angles. These, then, are the several radiologic changes that should be sought and are important clues to an increased pulmonary venous pressure. The chest roentgenogram can give other important diagnostic information. As left heart failure becomes more advanced, pleural effusions may occur that, if small, are more likely to be found radiologically than clinically. If the heart is globular or the cardiac silhouette is increasing with time, pericardial effusion is possible. An abnormal configuration of the left heart border, such as squaring-off or bulging, may raise the suspicion of ventricular aneurysm. A widening mediastinum or widening of the aortic shadow with abnormal separation due to medial calcification raises the question of dissection of the aorta. Obvious changes compatible with chronic obstructive pulmonary disease may make the interpretation of pulmonary rales much less specific. Electrocardiographic evaluation
Traditionally the electrocardiogram (ECG) has been used to identify certain dysrhythmic and pathophysiological abnormalities of the myocardium and conduction
tissue. Various rhythm disturbances, such as complete heart block and atrial arrhythmias, may be detected by physical examination, and flutter waves or giant cannon a-waves in the jugular veins, or variability of the first heart sound can occur. Electrocardiographic criteria are available for right and left atrial and ventricular hypertrophy. Persistence of ST-segment elevation following myocardial infarction is a clue to the presence of a ventricular aneurysm. The phenomena of a low-voltage QRS wave and electrical alternans may be associated with severe ventricular dysfunction and pencardial effusion with tamponade. Extensive pulmonary embolism can cause an electrocardiographic pattern of right ventricular strain, right bundle branch block and numerous supraventricular arrhythmias. More recently the ECG has been used to predict certain hemodynamic abnormalities. Heikkilii, Hugenholtz and Tabakin" have reported that the LVFP can be estimated from the P-wave terminal force (left atrial component) of the ECG. They analysed 40 acutely ill cardiac patients both hemodynamically and electrocardiographically, and found a significant inverse correlation between the Pwave terminal force in lead V1 and the mean LVFP, particularly in patients with acute left heart failure. Thus, the ECG can give useful information about the underlying pathophysiology. Its careful interpretation can confirm suspicions raised by physical examination and is occasionally the first indication of underlying disease. Other techniques
It is beyond the scope of this paper to discuss these techniques in detail. Only certain useful areas of application in the critically ill patient will be mentioned. Echocardiography has proved useful in differentiating ventricular dilatation and pericardial effusion. The flail posterior leaflet seen in papillary muscle rupture following acute myocardial infarction may be identified as the cause of mitral regurgitation or a murmur. The detection of wall motion abnormalities, aneurysm and wall thickness,
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and the prediction of hemodynamic abnormalities may prove useful with future development of the echocardiogram. Nuclear medicine techniques and computerized axial tomography are finding greater application in areas of patient assessment that heretofore required invasive diagnostic procedures. Hemodynamic evaluation
How has more sophisticated hemodynamic monitoring improved the clinical ability to assess cardiac function in the patient with acute myocardial infarction? Earlier hemodynamic assessment of the patient with infarction was attempted with the use of a CVP line, and identification of cardiac failure was based in part on the degree of elevation of the CVP. However, Forrester and colleagues18 studied 50 patients with simultaneous CVP and mean pulmonary capillary wedge pressure (PCW) measurement and found a poor correlation between the two values. Their study revealed not only a poor correlation when these pressures were initially measured, but also that these pressures could respond in a directionally different fashion to the same hemodynamic alteration. This should not be surprising since coronary artery disease is segmental and involves primarily the left ventricle. In health the right ventricle is a much more compliant chamber and so can accommodate a larger volume with a smaller rise in pressure. Since acute myocardial infarction involves the left ventricle primarily, marked changes in the LVEDP do not necessarily cause concomitant changes in the right ventricular end-diastolic pressure (RVEDP). Forrester and colleagues also evaluated the ability of the PCW to predict radiologic pulmonary congestion. They found that patients who had an elevated PCW had an abnormal chest roentgenogram, whereas those who had pressures less than approximately 18 mm Hg frequently had normal chest roentgenograms. The CVP, however, was of no help in predicting radiologic change, nor did it reflect volume shifts as a result of either volume infusion or diuresis. McHugh and associates19 com-
Table Il-Forrester, Diamond and Swan's clinical and hemodynamic classification of acute myocardial infarction23* Clinical status Class I
II Ill IV
Hypoperfusion -
Pulmonary congestion -
Hemodynamicstatust PCW . 18 mm Hg Cl . 2.2 1/mm -
+ + + + + + = present; - = absent. tPCW = mean pulmonary capillary wedge pressure; Cl = cardiac index.
-
+ +
prognostic insights but also practical therapeutic information. For example, the class III patient may be challenged with a volume load to raise the PCW, whereas the class IV patient may require a catecholamine or a vasodilator for a lowering of the PCW and an increase in the CI. The authors also looked at their ability to predict accurately the hemodynamic subset from the clinical criteria and found that their success depended on the particular class of patients under consideration. For example, those in class I, who would be judged to be free of pulmonary congestion and to have a normal cardiac index, were correctly classified clinically two thirds of the time; however, one third of these patients, when assessed with hemodynamic monitoring, actually belonged in a more advanced class of left ventricular dysfunction and were almost equally divided between class II and class III. In class II there was a 50% rate of error in clinical classification, with most of the misclassified patients belonging to class IV by hemodynamic criteria. This was even more significant when it was appreciated that all of the deaths in this group of patients occurred in those of hemodynamic class IV. Class III patients were usually correctly classified clinically except that the presence of hypoperfusion was underestimated. The sickest patients, those with class IV dysfunction, had parallel hemodynamic and clinical changes approximately 80% of the time. Here clinical errors were evenly divided between an underestimate of the PCW and an overestimate of the CI. These investigators have seriously applied themselves to the study of left ventricular dysfunction in acute infarction and have contributed tremendously to our understanding of the problem. Their findings are both illuminating and sobering since even they have a significant error in the clinical estimation of the severity of left ventricular dysfunction in acute myocardial infarction.
Conclusion In the critically ill patient clinical assessment can be likened to a pho-
tograph that is out of focus. It is usually sufficiently clear to allow one to see the nature of the subject. However, as in photography, where the use of the appropriate lens clarifies the picture, so in the critically ill patient hemodynamic monitoring adds considerable clarity to a difficult management problem. This paper has attempted to point out the qualitative nature of many symptoms and signs and the problems in their interpretation. The acquisition of hemodynamic data "on line" in the management of the critically ill patient does not obviate the need for clinical assessment but rather allows diagnosis and therapy to be more refined and quantitative. The present indications for hemodynamic monitoring in this patient population are outlined elsewhere in this symposium. References 1. SCHEIDT S, ASCHEIM R, KILLu' T
III: Shock after acute myocardial infarction. A clinical and hemodynamic profile. Am J Cardiol 26: 556, 1970 2. NoRRIs RM, BRANDT PWT, CAUGHEY DG, et al: A new coronary prognostic index. Lancet 1: 274, 1969 3. KiLuI' T, KIMBALL JT: A survey of the coronary care unit: concept and results. Prog Cardiovasc Dis 11: 45, 1968 4. FORRESTER JS, DIAMOND G, CHAT-
TERJEE K, et al: Medical therapy of acute myocardial infarction by application of hemodynamic subsets (two parts). N Engi J Med 295: 1356, 1404; 1976 5. SJOGREN A: Left heart failure in acute myocardial infarction. A clinical, haemodynamic and therapeutic study. Acta Med Scand suppi 510: 1970 6. MAJOR RH, DELP MH: Physical
7. 8.
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Diagnosis, 6th ed, Saunders, Philadelphia, 1962, pp 162-63 FoRGAcs P: Crackles and wheezes. Lancet 2: 203, 1967 BURCH GE, RAY CT: Mechanism of hepatojugular reflux test in congestive heart failure. Am Heart I 48: 373, 1954 TAVEL ME: Clinical Phonocardicgraphy and External Pulse Recording, 2nd ed, Year Bk Med, Chicago, 1972, pp 186-203 BRAUNWELL C: Gallop rhythm. Q I Med 4: 149, 1935 MAJOR RH, DELP MN: Physical Diagnosis, 6th ed, op cit, p 187 SEGMOUR J, BUCHER H: Reversed splitting of second heart sound in ischaemic heart disease. Br Heart I 27: 952, 1965
13. BURCH
GE,
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PHILLIPS JH: Clinical manifestations of papillary muscle dysfunction.
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Arch intern Med 112: 112, 1963 14. HEIKKILA J: Mitral incompetence complicating acute myocardial infarction. Br Heart J 29: 162, 1967 15. FORRESTER JS, DIAMOND G, FREED-
MAN S, et al: Silent mitral insufficiency in acute myocardial infarction. Circulation 44: 877, 1971 16. KORAN LM: The reliability of clinical methods, data and judgments (two parts). N Engi J Med 293: 642, 695; 1975 17. HEIKKILA
J,
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TABAKIN BS: Prediction of left heart filling pressure and its sequential change in acute myocardial infarction from the terminal force of the P wave. Br Heart J 35: 142, 1973 18. FORRESTER iS,
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HUGH TJ, et al: Filling pressures in the right and left sides of the heart in acute myocardial infarction. A reappraisal of central-venous-pressure monitoring. N Engi J Med 285: 190, 1971 19. MCHUGH TJ, FORRESTER iS, ADLER
L, et al: Pulmonary vascular congestion in acute myocardial infarction: hemodynamic and radiologic correlations. Ann intern Med 76: 29, 1972 20. DA Luz PL, SHUBIN H, WElL MH, et al: Pulmonary edema related to changes in colloid osmotic pulmonary artery wedge pressure in patients after acute myocardial infarction. Circulation 51: 350, 1975 21. CoHN JN: Blood pressure measurement in shock. Mechanism of inaccuracy in auscultatory and palpatory methods. JAMA 199: 972, 1967 22. RODBARD S: The significance of the intermediate Korotkoff sounds. Circulation 8: 600, 1953 23. FORRESTER iS, DIAMOND GA, SWAN
HJC: Correlative classification of clinical and hemodynamic function after acute myocardial infarction. Am J Cardiol 39: 137, 1977
I BOOKS continued from page 876 BIOLOGICAL IN DEVELOPMENTS STANDARDIZATION. Vol. 42. Proceeding of the Second General Meeting of European Society of Animal Cell Technology. Held at Maison des polytechniciens, Paris, France, 23-26 May 1978. Edited by the International Association of Biological Standardization. Acting Editors: R.H. Regamey, R. Spier and F. Horodniceanu. 210 pp. lIlust. S. Karger AG, Basel, 1979. $36, paperbound. ISBN 3-8055-2989-9 DIFFERENTIAL DIAGNOSIS. The Interpretation of Clinical Evidence. 3rd ed. A. McGehee Harvey, James Bordley, Ill and Jeremiah A. Barondess. 783 pp. W.B. Saunders Company, Philadelphia; W.B. Saunders Company Canada, Ltd., Toronto, 1979. $34.20. ISBN 0-72164562-3
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