Refer to: Oill PA, Bayer AS, Criley JM, et al: Infectious disease emergencies-Part II: Patients presenting with cardiac decompensation or circulatory insufficiency (shock), In Infectious disease emergencies-Teaching Conference, University of California, Los Angeles, and Harbor General Hospital, Torrance (Specialty Conference). West J Med 125:119-136, Aug 1976
Specialty Conference Moderator PHYLLIS A. OILL, MD
Discussants ARNOLD S. BAYER, MD J. MICHAEL CRILEY, MD ARNOLD H. BLAUFUSS, MD LARRY FISHER, MD This is a transcript of one of the regular teaching conferences in Infectious Diseases held weekly at Harbor General Hospital, Torrance, California. These conferences have been edited by Doctors Jerrold A. Turner, John Z. Montgomerie, Anthony W. Chow, Thomas T. Yoshikawa and Lucien B. Guze.
fectious Disease r nergencies
Inl
RT II: Pa tients Presenting with Cardiac Dekcompensation or Circulatory I-n ;ufficiency (Shock)
PA
PHYLLIS OILL, MD: * The second part of the symposium on infectious disease emergencies focuses on patients who present to an emergency department with cardiac decompensation or circulatory insufficiency (shock). Although there are numerous infectious processes that can cause this type of clinical presentation (see Table II-1), in this section we will review those diseases that affect the cardiovascular system primarily. Dr. Arnold Bayer will now begin the discussion by reviewing the clinical and laboratory aspects of infective endocarditis. Drs. Criley and Blaufuss will then discuss the cardiac and hemodynamic manifestations of this disease process. ARNOLD S. BAYER, MD: t Cardiac infections remain one of the most difficult problems, both diagnostically and therapeutically, for clinicians to cope with. The consequences of delayed recognition and treatment of these disorders are indeed life-threatening. There, perhaps, is nothing so challenging to a medical staff as a patient with acute deterioration of cardiac function caused by *Division of Infectious Diseases and Receiving-Emergency Department, Harbor General Hospital, Assistant Professor of Medicine, UCLA School of Medicine.
tFellow, Division of Infectious Diseases, Harbor General Hospital. Part II of a five part symposium. Part I published in July 1976. Parts III-V to be published in subsequent issues. Reprint requests to: Division of Infectious Diseases, Department of Medicine, Harbor General Hospital, 1000 West Carson Street, Torrance, CA 90509.
an infectious process. Such a situation not only calls upon a physician to treat the manifest cardiac failure, but also to recognize and manage the underlying infectious process with prompt and appropriate therapy; in addition, one must know when early surgical intervention is called for. In this section of the symposium, emphasis will be placed on the most important aspects of the evaluation and management of infective endocarditis and pericarditis. Additionally, the various causes of infectious myocarditis will be mentioned briefly.
Infective Endocarditis Some general comments should be emphasized about infective endocarditis. In the past 20 to 25 years, there has been a pronounced increase in the average age of patients with endocarditis, with over 50 percent now being above age 50.1 Also, in 40 percent of such patients there is neither a history nor clinical or autopsy evidence of antecedent cardiac disease.' The classification of endocarditis into acute and subacute forms tells one nothing more than the clinical course of the infection. It is now apparent that any organism can cause an acute, fulminant type of infection or, alternatively, more indolent, subacute clinical features.2 Fever is still the most common sign in infective THE WESTERN JOURNAL OF MEDICINE
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INFECTIOUS DISEASE EMERGENCIES-PART 11 ABBREVIATIONS USED IN TEXT AFB = acid-fast bacillus DIC = disseminated intravascular coagulation RHD = rheumatic heart disease
endocarditis, occurring in 90 to 95 percent of cases."', However, it must be remembered that fever can be minimal or absent in older patients, patienits with renal or cardiac failure or in persons who have received antibiotic therapy previously.' In the acute form of endocarditis, especially with rightsided involvement, cardiac murmurs may be minimal or absent.4 Additionally, it is often difficult to appreciate changing murmurs. However, if there is a distinct alteration in the quality or intensity of a murmur, this usually heralds substantial architectural damage to the infected valve.5 Of equal importance in this clinical situation is that the classical peripheral signs of endocarditis-such as Osler's nodes, Janeway lesions, Roth spots, splenomegaly and the likeare often absent.' Although these signs are imTABLE 11-1.-Infectious Diseases Presenting with Cardiac Decompensation or Circulatory Insufficiency (Shock)
Cardiac Infections Endocarditis Pericarditis Myocarditis Mediastinitis* Septic shock or febrile hypotension Gram-negative organisms Gram-positive organisms malaria especially falciparum Disseminated intravascular coagulation (DIC) secondary to infection Pneumonia with severe hypoxiat Infectious diarrheal syndromes-particularly staphylococcal enteritis, cholera, fulminant amebic colitis* Peritonitis* Anaphylaxis secondary to antibiotic therapyt *Will be discussed in Infectious Disease Emergencies, part IV: Patients presenting with gastrointestinal disorders. tWill be discussed in Infectious Disease Emergencies, part III: Patients presenting with respiratory distress syndromes.
TABLE 11-2.-Infective Endocarditis-Less Common Clinical Presentations Febrile stroke Renal failure of unknown cause Multilobed pneumonia Septic arthritis Arrhythmias or heart block
Polyarthritis Pericarditis Major artery embolus Thrombocytopenia
120
AUGUST 1976 * 125
* 2
portant to look for and significant if found, their absence should not dissuade one from the diagnosis of infective endocarditis. Most clinicians are aware of the usual presentations of endocarditis but it is worthwhile to keep in mind some less common modes of onset, many of which the housestaff here at Harbor General Hospital have been confronted with during the past 18 months (see Table 11-2). In patients with cardiac decompensation, the presence of these ancillary syndromes may alert physicians to an underlying endocarditis.3 The results of routine laboratory tests available at short notice may not be too useful in the early diagnosis of endocarditis. One that is simple, rapid and very helpful is the microscopic examination of a urine specimen; hematuria is found to be present in most patients with iendocarditis when it, is looked for repeatedly." 6 The laboratory test of paramount importance, of course, is a blood culture. In an urgent situation, where therapy will often be initiated empirically before the organism can be identified, four or five sets of cultures (aerobic and anaerobic) of blood specimens obtained from different venous sites are optimum.7'8 These can be taken a short time apart because the bacteremia tends to be more or less constant at a particular level for each individual case.3 In addition, cultures are most often positive on the first set.7-9 The purpose of multiple cultures is to identify those patients in whom bacteremia may be fluctuating at a relatively low level. Findings in recent studies continue to show the viridans and Group D streptococci as the most frequent microbial agents found in patients with endocarditis, followed by the staphylococci, both aureus and albus. These organisms make up 80 to 90 percent of those isolated in nonselected populations.'-3 9 However, in 173 recently reported patients with heroin-associated endocarditis,1'-16 staphylococci accounted for 94 of these cases, followed by Streptococcus viridans in only 19 cases. There were also 13 patients with aerobic Gram-negative bacillary endocarditis, 11 with Candida, 9 with Group D streptococci and 3 cases caused by microaerophilic streptococci. Consequently, one can see that knowledge of the population being examined will make a difference in the types of organisms that should be expected. In addition to drug abusers using intravenous administration, there are other clinical situations in
INFECTIOUS DISEASE EMERGENCIES-PART 11 TABLE 11-3.-Key Etiologic Associations in Infective Endocarditis Organism(s) Often Found
Clinical Situation
Alcoholism .......................... Narcotic abuse ............ ........... Hospital acquired ......... ........... Urologic or gynecologic manipulations ... Prosthetic cardiac valves Early (60 days postop) ..... ........ Viridans and Group D streptococci and penicillin-sensitive staphylococci Endocarditis with major embolus ....... Fungi, Gram-negative rods, staphylococci
which certain organisms tend to be found (see Table 11-3). In chronic alcoholics there is a propensity for pneumococcal endocarditis to develop,'7"18 while in patients in hospital endocarditis with penicillinresistant streptococci and staphylococci as well as aerobic Gram-negative rods tend to develop." 20 In patients with endocarditis where there have been earlier urologic or gynecologic manipulations, the Enterococcus is often the cause.2' In cases where the initial presentation is a major arterial embolism, staphylococci, fungi and Gramnegative rods (both aerobic and anaerobic) predominate as etiological agents.20 22-24 In the presence of a prosthetic cardiac valve, one sees two distinct distributions of organisms causing endocarditis, by separation of the cases to an early (less than 60 days postoperative) versus late (more than 60 days postoperative) form.25 In the first group, penicillin-resistant staphylococci, especially the coagulase negative variety (Staphylococcus albus); Gram-negative rods, and fungi, especially Candida species, are frequent isolates, while in the latter group, viridans and Group D streptococci and staphylococci (which may be penicillin-sensitive) are usually seen.25 Culture negative endocarditis makes up, on an average, 15 percent of proven cases of infective endocarditis.822 The most common cause of this phenomenon is probably previous antibiotic therapy.8 Another cause is fungal endocarditis where the fungemia tends not to be as constant as in bacterial endocarditis.26 Coxiella burnetti (Q fever), psittacosis and viruses have been described to cause an acute destructive valvulitis' 22'27-29 and will also present as culture-negative endocarditis. Since ordinary laboratory techniques will not isolate these agents, the diagnosis is best made by specific serologic tests. Endocarditis caused by anaerobic organisms may be missed unless proper transport and cultural techniques are used.22'24
In patients with acute cardiac decompensation in whom endocarditis is suspected, a clinician often has to initiate antibiotic therapy either before the results of blood cultures are known, or before definitive sensitivity testing is done. Therefore, an understanding of what organisms to anticipate in a given patient is very helpful. It is a tenet in the treatment of infective endocarditis that a bactericidal agent or agents be used.12 Also, in urgent situations, therapy designed to achieve the most rapid killing should be sought. For penicillin-sensitive streptococci, penicillin alone in doses of 15 to 20 million units per day, administered intravenously for four to six weeks is usually adequate.2 However, when there has been cardiac failure, the addition of an aminoglycoside such as streptomycin may be important because this combination increases the rate of killing.30 If a patient has a definitive history of a major penicillin allergy (such as anaphylaxis or giant urticaria), one should substitute one of several regimens that have been efficacious against penicillin-sensitive streptococcal endocarditis. Cephalothin (90 to 150 mg per kg of body weight per day given intravenously), vancomycin (30 mg per kg of body weight per day given intravenously) and the combination of erythromycin (60 mg per kg of body weight per day given intravenously) plus streptomycin (30 mg per kg of body weight per day given intramuscularly) have each been utilized in penicillin allergic patients.3' If a patient has a history of a minor allergy to penicillin, such as skin rash, skin tests can be carried out with the major and minor antigenic determinants of penicillin to predict the likelihood of anaphylaxis.32 In the absence of this facility, one should either use an alternate therapeutic regimen or with the help of an allergist, institute rapid penicillin densensitization.2 In recent studies of Group D streptococcal enTHE WESTERN JOURNAL OF MEDICINE
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INFECTIOUS DISEASE EMERGENCIES-PART II
docarditis, nearly half of the isolates from such cases are not true enterococci but are Streptococcus bovis.33-36 This is extremely important because S. bovis is usually sensitive to penicillin as well as to a whole host of other single antibiotics. The mortality in endocarditis due to this organism is fairly low, whereas true enterococci (S. faecalis) are difficult to eradicate with single antibiotics, require combination chemotherapy and result in mortality three times that of S. bovis endocarditis.33-3¢ For S. bovis, penicillin in doses of 15 to 20 million units per day given intravenously is the treatment of choice. There is some evidence that the addition of an aminoglycoside will enhance the rate of killing.34'37 For Streptococcus faecalis, the regimens of choice are combinations of penicillin or ampicillin (150 to 250 mg per kg of body weight per day given intravenously) plus an aminoglycoside.2,21,38,39-41 For patients allergic to penicillin, vancomycin plus an aminoglycoside should be used.40'42 When staphylococcal endocarditis is suspected
or diagnosed, therapy with penicillinase-resistant antibiotics should be initiated. Methicillin (100 to 200 mg per kg of body weight per day given intravenously), nafcillin (50 to 90 mg per kg of body weight per day given intravenously) or cephalothin (90 to 150 mg per kg of body weight per day) can be used." 2 In patients allergic to penicillin, vancomycin should be given."2'3'43'44 For a patient who presents with cardiac decompensation and presumed bacterial endocarditis and is not an abuser of drugs taken intravenously, expectant therapy with penicillin and streptomycin is usually adequate.' This also applies to such similar cases as those of patients in whom blood cultures remain negative. For drug users, staphylococci, Group D and nonGroup D streptococci, and aerobic Gram-negative rods must be anticipated and appropriate antimicrobial therapy for all these potential pathogens should be initiated, at least until positive blood cultures have returned. An initial regimen such as penicillin-methicillin-gentamicin should
TABLE 11-4.-Overall Mortality in Treated Cases of Infective Endocarditis in the Recent Literature* Organism
Cases
Deaths
Percent Died
18
134 Streptococcus viridans9,l4,l6,l9,25,30,36. Streptococcus bovist33-36 ............................ 37 Streptococcus faecalist33,35,36 ........................ 26 Penicillin-sensitive anaerobes24,45 ..................... 36 Prosthetic valve endocarditis (excluding fungal)25. Gram-negative rods
45
24 5 9 8 18
14 32 22 40
Aerobic23'46 ....................................... Anaerobic (penicillin resistant)t24'25 .................. Staphylococcus aureus'42025 ...................... Fungal (mainly Candida)26X48 .......................
30 27 87
17 11 29
57 41 33
155
140
90
Includes both appropriate antimicrobial as well as surgical therapy where indicated. tFrom recent series in which S. bovis is adequately differentiated from S. faecalis. tBacteroides fragilis mainly.
TABLE 11-5.-Adverse Factors in Survival of Patients with Infective Endocarditis Example
Virulent organism Old age
..................
Staphylococci, GNR, pneumococci
...........................
Serious systemic disease(s) .......... Serious underlying cardiac disease. Aortic or mitral valve involvement Prosthetic valve involvement ......... Propensity of organism to embolize .... Presence of paravalvular infection .... Difficulty killing organism ........... Toxicity of therapy ................. Cardiac surgery often necessary ....... Presence of congestive failure .........
Diabetes mellitus, narcotic addiction, alcoholism, cancer Hypertension, coronary artery disease, rheumatic heart disease
Fungi, anaerobes, staphylococci Ring abscess, myocardial abscess Streptococcus faecalis, penicillin-resistant, GNR anaerobes, fungi, Q-fever Aminoglycosides, amphotericin B Anaerobic and aerobic GNR, fungi, Q-fever
GNR = Gram-negative rods
122
AUGUST 1976
*
125
*
2
INFECTIOUS DISEASE EMERGENCIES-PART 11
be effective. In patients allergic to penicillin, a combination of vancomycin and gentamicin could be substituted with similar salutory effects. In anaerobic bacterial endocarditis in which the organisms are sensitive to penicillin, cures have been achieved with this drug.24'45 However, if the organism is resistant to penicillin, such as Bacteroides fragilis, or if a patient is truly allergic to penicillin, bacteriostatic agents such as clindamycin or chloramphenicol would have to be used. The success with these agents has been variable. 24,45 For aerobic Gram-negative bacillary endocarditis, drugs such as gentamicin, kanamycin, chloramphenicol, ampicillin, tobramycin and carbenicillin have been used alone or in various combinations according to sensitivity data.23'40 Amphotericin B remains the only useful agent for fungal endocarditis.1,16,47 The response to medical therapy of the last three forms of infective endocarditis has been disappointing, and surgical intervention frequently is required. Although in patients with endocarditis due to penicillin-sensitive organisms there is a recovery rate of 75 to 95 percent, for those in whom other types of organisms are present there is much higher mortality (see Table 11-4). This ranges from 30 to 40 percent mortality for Staphylococcus aureus, true enterococcal, penicillin-resistant anaerobic Gram-negative rod and prosthetic valve endocarditis (of all bacterial causes) to about 90 percent mortality for fungal endocarditis reported from previous series. However, a recent report of 11 patients with Candida endocarditis yielded much higher survival rates than have previously been cited.264748 In this study, early diagnosis and surgical intervention (within 48 hours of confirmation of the diagnosis) plus vigorous intraoperative and prolonged, postoperative therapy with amphotericin B, resulted in eight cures. The somewhat lower mortality rates in recent series of staphylococcal endocarditis' 14"16'20 reflect the increasing proportion of heroin addicts with this disease and the frequent occurrence of tricuspid involvement in such patients. The addict population tends to have reasonably good nutritional status without significant medical problems before endocarditis develops,'4 and infection of the tricuspid valve carries a better prognosis than endocarditis of either aortic or mitral valves'4 because of the more benign hemodynamic consequences
and lack of direct access of septic emboli to more vital organs. In addition to the virulence of the organism involved,"'14 other factors tend to increase mortality in cases of infective endocarditis (see Table II-5). In older patients, for a variety of reasons, there is a higher death rate."' 4 Patients with serious underlying cardiac or systemic diseases do not fare as well as those without these conditions. In those with aortic or mitral involvement and those in whom congestive heart failure develops there is a worse prognosis."'4'49 If there is a paravalvular infection, such as a valve-ring abscess or a myocardial abscess, or if there has been peripheral embolization causing vital organ damage or metastatic abscesses, the survival rate is significantly diminished."'4'20'50 Also, if the offending organism is difficult to eradicate with presently available therapy or the therapy intrinsically has significant toxicity, as with the aminoglycosides and amphotericin B, the mortality is exceedingly high.'12",23,24,45,51,52 The principal causes of death in patients with infective endocarditis varies somewhat, depending on which valves of the heart are involved. In those with principally left'sided involvement, cardiovascular causes, mainly congestive heart failure, predominate, with neurologic complications due to central nervous system embolization of lesser importance.50 In contrast, those with rightsided infective endocarditis die usually from both generalized as well as localized infections (principally pneumonia and meningitis) and less often from congestive heart failure.'8
The Hemodynamic Basis for Atypical Physical Findings in Acute Valvular Regurgitation J. MICHAEL CRILEY, MD* and ARNOLD H. BLAUFUSS, MD:t Infective endocarditis poses two major challenges: to isolate and treat the organism quickly and effectively, and to localize and assess the hemodynamic significance of the cardiovascular lesion or lesions. Dr. Bayer has dealt with the bacteriological aspects, and these remarks will concern themselves with valvular lesions. Unlike rheumatic heart disease, infective endocarditis may create severe valvular incompetence in a short time, and as a result the impact on the patient may be quite different and the resulting clinical findings may be quite confusing. The fol*Chief, Division of Cardiology, Harbor General Hospital, Professor of Medicine, UCLA School of Medicine. tFellow, Division of Cardiology, Harbor General Hospital.
THE WESTERN JOURNAL OF MEDICINE
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INFECTIOUS DISEASE EMERGENCIES-PART 11
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Figure Il-1.-Chronic Mitral Regurgitation-Left, left atrial (LA)/ and left ventricular (LV) pressure in a 21-year-old minimally symptomatic man with a history of recurrent acute rheumatic fever. Car at The left atrial ''V'' waves (V) are prominent, and followed sequentially by a rapid 'y' descent and rapid filling wave as the large volume within the atrium is rapidly expelled into the ventricle. The phonocardiogram shows an intact first sound (I), a holosystolic murmur (sm) and a prominent third heart sound (3). The third sound results from the rapid early diastolic inflow into the ventricle. There is no S-4. and the a-rial contraction wave (a) is not prominent. Time lines -=.04 sec. Right, a low frequency phonocardiogram (upper panel) shows the third heart sound (3), while a medium frequency recording (lower panel). better shows the systolic murmur (sm) which occupies all of systole and on some cycles continues after the second sound (2). CAR-carotid pulse tracing.
lowing is a summary of our findings in a group of 16 patients with infective endocarditis studied by cardiac catheterization, phonocardiography and echocardiography at Harbor General Hospital in the past three years. Tricuspid regurgitation, in its usual setting in rheumatic heart disease (RHD), produces a left parasternal systolic murmur with inspiratory augmentation, large V waves and a pulsatile liver. Many of these findings in patients with RHD are due to the presence of pulmonary hypertension, resulting from concurrent mitral valvular disease. In acute infective endocarditis, there may be only a soft early systolic murmur (or no murmur at all) and a normal venous pressure unless septic pulmonary emboli produce significant pulmonary vascular obstruction to cause right ventricular pressure overload. Mitral regurgitation in RHD (see Figure II-1) is associated with a holosystolic apical murmur, an early diastolic gallop sound (S-3) and a volume overload to the left atrium and ventricle resulting in gradual enlargement of these two chambers over a period of time. Significant pulmonary hypertension is unusual, since the large left atrium can accept the regurgitant volume quite well. 124
AUGUST 1976 * 125 * 2
However, acute mitral regurgitation (see Figure 11-2) has a devastating impact on the relatively noncompliant left atrium, raising its pressure to 75 to 100 mm of mercury in systole. To make matters worse, the left ventricle is also limited in its ability to accept a volume load, and the response is an increase in diastolic pressure. Therefore the left atrium is subjected to double jeopardy, a high systolic volume and pressure which it cannot get rid of in diastole. The result is a mitral stenosis-like pulmonary hypertension, pulmonary congegtion and pulmonary arterial hypertension. The murmur may be mistaken for an ejection murmur, and accompanied by a presystolic gallop sound (S-4). The reason for the unusual quality of the murmur is that the noncompliant left atrium "refuses" any more regurgitant blood in late systole because its pressure rivals the end systolic left ventricular pressure. The S-4 results from the relatively large atrial systolic contribution to the filling of the noncompliant left ventricle. Aortic regurgitation may present very atypical clinical features when the lesion occurs acutely. A clinician who expects the bounding "water hammer" pulse, enlarged hyperactive left ven-
INFECTIOUS DISEASE EMERGENCIES-PART II
tricle, long decrescendo diastolic murmur and two-phase Austin Flint rumble (see Figure 11-3) may be surprised by the unusual features of acute, sudden onset aortic regurgitation. In infective endocarditis, aortic valvular destruction may occur almost instantaneously, and the left ventricle cannot adjust to the increased diastolic volume load. The noncompliant ventricle consequently exhibits a notably elevated diastolic pressure which may exceed left atrial pressure shortly after the mitral valve opens, resulting in preclosure of the mitral valve (see Figure II-4). This preclosure leads to obliteration of the first heart sound, and frequently causes a loud middiastolic murmur as the valve closes while a large
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Figure 11-2.-Acute Mitral Regurgitation-In contrast to the patient illustrated in Figure I-1, this 48-year-old man is severely symptomatic with pronounced dyspnea and orthopnea of sudden onset during a febrile illness. Findings on an x-ray film of the chest were interpreted as bilateral pneumonia, and the heart murmur was initially thought to be due to aortic stenosis because of its medium length crescendo-decrescendo character and associated fourth heart sound. Six blood cultures were positive for group D alpha streptococcus, and he was successfully treated with penicillin and streptomycin. His hemodynamic status only permitted bed-tochair activity, and cardiac catheterization was carried out for evaluation of probable ruptured chordae tendineae. He was found to have pronounced pulmonary hypertension, striking "V" waves in the left atrium of over 100 mm of mercury and pronounced elevated left ventricular end diastolic pressure (33 mm of mercury) with prominent "a" waves. The apical systolic murmur (sm) ended well before the second sound (2, dashed line) because the left atrial pressure was sufficiently high to impede late systolic regurgitation. The fourth sound -(4) resulted from a vigorous atrial contraction (a). A soft third sound (3) was recorded, but not easily heard. Time lines=.04 sec. Angiography showed a flail anterior mitral leaflet. Valve replacement was carried out, and the patient is
currently asymptomatic.
volume of blood is leaving the left atrium. The Austin Flint murmur always implies significant aortic regurgitation, but when confined to middiastole and associated with an attenuated or absent first heart sound, it is indicative of very severe disease. The rapid elevation of left ventricular diastolic pressure may abbreviate the aortic regurgitant murmur as well as artificially support the aortic diastolic pressure, and consequently attenuate two valuable signs of aortic regurgitation.
Echocardiography Echocardiography may be extremely helpful in identifying those patients described above with endocarditis and acute mitral insufficiency. Instead of a thickened and often restricted anterior mitral leaflet as usually seen in rheumatic mitral insufficiency (see Figure 11-5), the anterior mitral leaflet in endocarditic mitral regurgitation will be thin and delicate with increased excursion (see Figure 11-6). When rupture of chordae tendineae occurs, the anterior leaflet excursion may be notably exaggerated. In addition, vibrating echoes continuous with the anterior mitral leaflet may identify mitral valve vegetations. It should be noted that similar findings are seen on the tricuspid valve and should be looked for in patients in whom right-sided infective endocarditis is suspected. Similarly, echocardiography can be extremely helpful in assessing the impact of aortic regurgitation (see Figures 11-7, 11-8, 11-9). The presence of the triad of fluttering of the anterior mitral valve preclosure, and large excursions of the left ventricular walls, is diagnostic of severe valvular incompetence and indicative of a poor outcome without surgical intervention. Occasionally, vibrating echoes in the aortic root at the level of the aortic valve may identify vegetations on the cusps. In addition vibrating echoes in the left ventricular outflow tract may suggest the presence of aortic cusp vegetations with prolapse into the left ventricular outflow tract (see Figure 11-8). The ventricular dimensions and hyperkinesis of the septum and posterior left ventricular wall are indistinguishable in acute severe mitral and aortic insufficiency, as both present a sudden volume overload to the left ventricle. Particularly noteworthy in the presence of severe valvular incompetence is early diastolic diastasis or flattening of the left side of the interventricular septum and left ventricular posterior wall (see Figure II9) as the ventricle reaches maximum compliance THE WESTERN JOURNAL OF MEDICINE
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INFECTIOUS DISEASE EMERGENCIES-PART II
ing diaphragmatic pleura it is not uncommon for the pain to be referred to the left supraclavicular area. It may have the distinction of being intensified by swallowing due to involvement of the esophagus. Rarely the pain is throbbing and synchronous with the heart beat. The primary feature noted on physical examination of patients with acute pericarditis is the presence of a pericardial friction rub. Typically the rub is triphasic, consisting of a presystolic component corresponding to atrial systole, a systolic component and an early diastolic component. Fever is common, as is tachycardia. If the pericarditis is associated with a significant effusion, the friction rub may be obliterated with the presence, then, of an increased area of cardiac dullness, muffled heart sounds, cyanosis (occasionally) and a paradoxical pulse. The presence of pulsus paradoxus indicates a significant pericardial effusion. Physical findings in a patient with pericardial tamponade are dependent on the hemodynamic deficits present. Neck vein distention is prominent with a rapid x descent in the jugular venous pulse. The y descent is not prominent as is seen in constrictive pericarditis.53 Tachycardia is usually present to maintain cardiac output and as the stage of tamponade is approached there is a drop in pulse pressure. A complete discussion of the clinical, electrocardiographic, radiologic and pathophysiologic manifestations of pericarditis, pericardial effusion and tamponade can be found in a symposium previously published in this
in early diastole because of the large volume overload. Small posterior pericardial effusions may also be seen (see Figure 11-9), but large effusions are distinctly rare in infective endocarditis.
Summary and Conclusions The confusing physical findings presented by patients with infective endocarditis should not mislead a physician into assuming that there is extensive myocardial damage and not severe valvular regurgitation because of the paucity of murmurs, loud gallop sounds and soft or absent first sound. Echocardiograms have been invaluable in assessing valve -function and provide an accurate noninvasive method for serially studying the size and performance of the left ventricle. It is hoped that this treatise on the hemodynamic basis for atypical findings will stimulate a more aggressive use of noninvasive instruments, including the stethoscope, in the management of these desperately ill patients. DR. OILL: Before Dr. Bayer discusses infectious pericarditis and myocarditis, I will briefly review the clinical signs and symptoms associated with these diseases. In patients with infectious pericarditis there may be evidence of acute pericarditis alone or significant pericardial effusion and tamponade may be noted in addition. In acute pericarditis, precordial pain is common-sometimes mimicking a myocardial infarction-and is frequently affected by respiratory movements, cough and position. Because of inflammation of the adjoin-
journal.54 The typical clinical features of myocarditis are -200-
Figure 11-3.
-
Chronic Aortic
_
__
__
_
__
_
Regurgitation - A 30-year-old woman with childhood rheu2 APEX matic fever was minimaly2RC symptomatic, but was noted to have progressive cardiac enem l i cLaCS largement on serial x-ray studies of the chest. The bounding -100arterial pulses are shown in the aortic (Ao) pressure of 175/40. The left ventricular end / diastolic pressure is minimally elevated (18 mm of mercury). A loud ejection systolic murmur (sm) due to high flow was heard in the aortic area (left panel, sm), and a high-pitched early diastolic murmur of aor--___________________-----__ tic regurgitation (edm) was heard at both sides of the sternum. At the apex (right panel) a two component Austin Flint murmur was heard, indicated forward flow across a functionally restricted mitral orifice throughout all of diastole.
1 26
AUGUST 1976 * 125 * 2
INFECTIOUS DISEASE EMERGENCIES-PART 11
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Specialty Conference Moderator PHYLLIS A. OILL, MD
Discussants ARNOLD S. BAYER, MD J. MICHAEL CRILEY, MD ARNOLD H. BLAUFUSS, MD LARRY FISHER, MD This is a transcript of one of the regular teaching conferences in Infectious Diseases held weekly at Harbor General Hospital, Torrance, California. These conferences have been edited by Doctors Jerrold A. Turner, John Z. Montgomerie, Anthony W. Chow, Thomas T. Yoshikawa and Lucien B. Guze.
fectious Disease r nergencies
Inl
RT II: Pa tients Presenting with Cardiac Dekcompensation or Circulatory I-n ;ufficiency (Shock)
PA
PHYLLIS OILL, MD: * The second part of the symposium on infectious disease emergencies focuses on patients who present to an emergency department with cardiac decompensation or circulatory insufficiency (shock). Although there are numerous infectious processes that can cause this type of clinical presentation (see Table II-1), in this section we will review those diseases that affect the cardiovascular system primarily. Dr. Arnold Bayer will now begin the discussion by reviewing the clinical and laboratory aspects of infective endocarditis. Drs. Criley and Blaufuss will then discuss the cardiac and hemodynamic manifestations of this disease process. ARNOLD S. BAYER, MD: t Cardiac infections remain one of the most difficult problems, both diagnostically and therapeutically, for clinicians to cope with. The consequences of delayed recognition and treatment of these disorders are indeed life-threatening. There, perhaps, is nothing so challenging to a medical staff as a patient with acute deterioration of cardiac function caused by *Division of Infectious Diseases and Receiving-Emergency Department, Harbor General Hospital, Assistant Professor of Medicine, UCLA School of Medicine.
tFellow, Division of Infectious Diseases, Harbor General Hospital. Part II of a five part symposium. Part I published in July 1976. Parts III-V to be published in subsequent issues. Reprint requests to: Division of Infectious Diseases, Department of Medicine, Harbor General Hospital, 1000 West Carson Street, Torrance, CA 90509.
an infectious process. Such a situation not only calls upon a physician to treat the manifest cardiac failure, but also to recognize and manage the underlying infectious process with prompt and appropriate therapy; in addition, one must know when early surgical intervention is called for. In this section of the symposium, emphasis will be placed on the most important aspects of the evaluation and management of infective endocarditis and pericarditis. Additionally, the various causes of infectious myocarditis will be mentioned briefly.
Infective Endocarditis Some general comments should be emphasized about infective endocarditis. In the past 20 to 25 years, there has been a pronounced increase in the average age of patients with endocarditis, with over 50 percent now being above age 50.1 Also, in 40 percent of such patients there is neither a history nor clinical or autopsy evidence of antecedent cardiac disease.' The classification of endocarditis into acute and subacute forms tells one nothing more than the clinical course of the infection. It is now apparent that any organism can cause an acute, fulminant type of infection or, alternatively, more indolent, subacute clinical features.2 Fever is still the most common sign in infective THE WESTERN JOURNAL OF MEDICINE
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INFECTIOUS DISEASE EMERGENCIES-PART 11 ABBREVIATIONS USED IN TEXT AFB = acid-fast bacillus DIC = disseminated intravascular coagulation RHD = rheumatic heart disease
endocarditis, occurring in 90 to 95 percent of cases."', However, it must be remembered that fever can be minimal or absent in older patients, patienits with renal or cardiac failure or in persons who have received antibiotic therapy previously.' In the acute form of endocarditis, especially with rightsided involvement, cardiac murmurs may be minimal or absent.4 Additionally, it is often difficult to appreciate changing murmurs. However, if there is a distinct alteration in the quality or intensity of a murmur, this usually heralds substantial architectural damage to the infected valve.5 Of equal importance in this clinical situation is that the classical peripheral signs of endocarditis-such as Osler's nodes, Janeway lesions, Roth spots, splenomegaly and the likeare often absent.' Although these signs are imTABLE 11-1.-Infectious Diseases Presenting with Cardiac Decompensation or Circulatory Insufficiency (Shock)
Cardiac Infections Endocarditis Pericarditis Myocarditis Mediastinitis* Septic shock or febrile hypotension Gram-negative organisms Gram-positive organisms malaria especially falciparum Disseminated intravascular coagulation (DIC) secondary to infection Pneumonia with severe hypoxiat Infectious diarrheal syndromes-particularly staphylococcal enteritis, cholera, fulminant amebic colitis* Peritonitis* Anaphylaxis secondary to antibiotic therapyt *Will be discussed in Infectious Disease Emergencies, part IV: Patients presenting with gastrointestinal disorders. tWill be discussed in Infectious Disease Emergencies, part III: Patients presenting with respiratory distress syndromes.
TABLE 11-2.-Infective Endocarditis-Less Common Clinical Presentations Febrile stroke Renal failure of unknown cause Multilobed pneumonia Septic arthritis Arrhythmias or heart block
Polyarthritis Pericarditis Major artery embolus Thrombocytopenia
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AUGUST 1976 * 125
* 2
portant to look for and significant if found, their absence should not dissuade one from the diagnosis of infective endocarditis. Most clinicians are aware of the usual presentations of endocarditis but it is worthwhile to keep in mind some less common modes of onset, many of which the housestaff here at Harbor General Hospital have been confronted with during the past 18 months (see Table 11-2). In patients with cardiac decompensation, the presence of these ancillary syndromes may alert physicians to an underlying endocarditis.3 The results of routine laboratory tests available at short notice may not be too useful in the early diagnosis of endocarditis. One that is simple, rapid and very helpful is the microscopic examination of a urine specimen; hematuria is found to be present in most patients with iendocarditis when it, is looked for repeatedly." 6 The laboratory test of paramount importance, of course, is a blood culture. In an urgent situation, where therapy will often be initiated empirically before the organism can be identified, four or five sets of cultures (aerobic and anaerobic) of blood specimens obtained from different venous sites are optimum.7'8 These can be taken a short time apart because the bacteremia tends to be more or less constant at a particular level for each individual case.3 In addition, cultures are most often positive on the first set.7-9 The purpose of multiple cultures is to identify those patients in whom bacteremia may be fluctuating at a relatively low level. Findings in recent studies continue to show the viridans and Group D streptococci as the most frequent microbial agents found in patients with endocarditis, followed by the staphylococci, both aureus and albus. These organisms make up 80 to 90 percent of those isolated in nonselected populations.'-3 9 However, in 173 recently reported patients with heroin-associated endocarditis,1'-16 staphylococci accounted for 94 of these cases, followed by Streptococcus viridans in only 19 cases. There were also 13 patients with aerobic Gram-negative bacillary endocarditis, 11 with Candida, 9 with Group D streptococci and 3 cases caused by microaerophilic streptococci. Consequently, one can see that knowledge of the population being examined will make a difference in the types of organisms that should be expected. In addition to drug abusers using intravenous administration, there are other clinical situations in
INFECTIOUS DISEASE EMERGENCIES-PART 11 TABLE 11-3.-Key Etiologic Associations in Infective Endocarditis Organism(s) Often Found
Clinical Situation
Alcoholism .......................... Narcotic abuse ............ ........... Hospital acquired ......... ........... Urologic or gynecologic manipulations ... Prosthetic cardiac valves Early (60 days postop) ..... ........ Viridans and Group D streptococci and penicillin-sensitive staphylococci Endocarditis with major embolus ....... Fungi, Gram-negative rods, staphylococci
which certain organisms tend to be found (see Table 11-3). In chronic alcoholics there is a propensity for pneumococcal endocarditis to develop,'7"18 while in patients in hospital endocarditis with penicillinresistant streptococci and staphylococci as well as aerobic Gram-negative rods tend to develop." 20 In patients with endocarditis where there have been earlier urologic or gynecologic manipulations, the Enterococcus is often the cause.2' In cases where the initial presentation is a major arterial embolism, staphylococci, fungi and Gramnegative rods (both aerobic and anaerobic) predominate as etiological agents.20 22-24 In the presence of a prosthetic cardiac valve, one sees two distinct distributions of organisms causing endocarditis, by separation of the cases to an early (less than 60 days postoperative) versus late (more than 60 days postoperative) form.25 In the first group, penicillin-resistant staphylococci, especially the coagulase negative variety (Staphylococcus albus); Gram-negative rods, and fungi, especially Candida species, are frequent isolates, while in the latter group, viridans and Group D streptococci and staphylococci (which may be penicillin-sensitive) are usually seen.25 Culture negative endocarditis makes up, on an average, 15 percent of proven cases of infective endocarditis.822 The most common cause of this phenomenon is probably previous antibiotic therapy.8 Another cause is fungal endocarditis where the fungemia tends not to be as constant as in bacterial endocarditis.26 Coxiella burnetti (Q fever), psittacosis and viruses have been described to cause an acute destructive valvulitis' 22'27-29 and will also present as culture-negative endocarditis. Since ordinary laboratory techniques will not isolate these agents, the diagnosis is best made by specific serologic tests. Endocarditis caused by anaerobic organisms may be missed unless proper transport and cultural techniques are used.22'24
In patients with acute cardiac decompensation in whom endocarditis is suspected, a clinician often has to initiate antibiotic therapy either before the results of blood cultures are known, or before definitive sensitivity testing is done. Therefore, an understanding of what organisms to anticipate in a given patient is very helpful. It is a tenet in the treatment of infective endocarditis that a bactericidal agent or agents be used.12 Also, in urgent situations, therapy designed to achieve the most rapid killing should be sought. For penicillin-sensitive streptococci, penicillin alone in doses of 15 to 20 million units per day, administered intravenously for four to six weeks is usually adequate.2 However, when there has been cardiac failure, the addition of an aminoglycoside such as streptomycin may be important because this combination increases the rate of killing.30 If a patient has a definitive history of a major penicillin allergy (such as anaphylaxis or giant urticaria), one should substitute one of several regimens that have been efficacious against penicillin-sensitive streptococcal endocarditis. Cephalothin (90 to 150 mg per kg of body weight per day given intravenously), vancomycin (30 mg per kg of body weight per day given intravenously) and the combination of erythromycin (60 mg per kg of body weight per day given intravenously) plus streptomycin (30 mg per kg of body weight per day given intramuscularly) have each been utilized in penicillin allergic patients.3' If a patient has a history of a minor allergy to penicillin, such as skin rash, skin tests can be carried out with the major and minor antigenic determinants of penicillin to predict the likelihood of anaphylaxis.32 In the absence of this facility, one should either use an alternate therapeutic regimen or with the help of an allergist, institute rapid penicillin densensitization.2 In recent studies of Group D streptococcal enTHE WESTERN JOURNAL OF MEDICINE
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INFECTIOUS DISEASE EMERGENCIES-PART II
docarditis, nearly half of the isolates from such cases are not true enterococci but are Streptococcus bovis.33-36 This is extremely important because S. bovis is usually sensitive to penicillin as well as to a whole host of other single antibiotics. The mortality in endocarditis due to this organism is fairly low, whereas true enterococci (S. faecalis) are difficult to eradicate with single antibiotics, require combination chemotherapy and result in mortality three times that of S. bovis endocarditis.33-3¢ For S. bovis, penicillin in doses of 15 to 20 million units per day given intravenously is the treatment of choice. There is some evidence that the addition of an aminoglycoside will enhance the rate of killing.34'37 For Streptococcus faecalis, the regimens of choice are combinations of penicillin or ampicillin (150 to 250 mg per kg of body weight per day given intravenously) plus an aminoglycoside.2,21,38,39-41 For patients allergic to penicillin, vancomycin plus an aminoglycoside should be used.40'42 When staphylococcal endocarditis is suspected
or diagnosed, therapy with penicillinase-resistant antibiotics should be initiated. Methicillin (100 to 200 mg per kg of body weight per day given intravenously), nafcillin (50 to 90 mg per kg of body weight per day given intravenously) or cephalothin (90 to 150 mg per kg of body weight per day) can be used." 2 In patients allergic to penicillin, vancomycin should be given."2'3'43'44 For a patient who presents with cardiac decompensation and presumed bacterial endocarditis and is not an abuser of drugs taken intravenously, expectant therapy with penicillin and streptomycin is usually adequate.' This also applies to such similar cases as those of patients in whom blood cultures remain negative. For drug users, staphylococci, Group D and nonGroup D streptococci, and aerobic Gram-negative rods must be anticipated and appropriate antimicrobial therapy for all these potential pathogens should be initiated, at least until positive blood cultures have returned. An initial regimen such as penicillin-methicillin-gentamicin should
TABLE 11-4.-Overall Mortality in Treated Cases of Infective Endocarditis in the Recent Literature* Organism
Cases
Deaths
Percent Died
18
134 Streptococcus viridans9,l4,l6,l9,25,30,36. Streptococcus bovist33-36 ............................ 37 Streptococcus faecalist33,35,36 ........................ 26 Penicillin-sensitive anaerobes24,45 ..................... 36 Prosthetic valve endocarditis (excluding fungal)25. Gram-negative rods
45
24 5 9 8 18
14 32 22 40
Aerobic23'46 ....................................... Anaerobic (penicillin resistant)t24'25 .................. Staphylococcus aureus'42025 ...................... Fungal (mainly Candida)26X48 .......................
30 27 87
17 11 29
57 41 33
155
140
90
Includes both appropriate antimicrobial as well as surgical therapy where indicated. tFrom recent series in which S. bovis is adequately differentiated from S. faecalis. tBacteroides fragilis mainly.
TABLE 11-5.-Adverse Factors in Survival of Patients with Infective Endocarditis Example
Virulent organism Old age
..................
Staphylococci, GNR, pneumococci
...........................
Serious systemic disease(s) .......... Serious underlying cardiac disease. Aortic or mitral valve involvement Prosthetic valve involvement ......... Propensity of organism to embolize .... Presence of paravalvular infection .... Difficulty killing organism ........... Toxicity of therapy ................. Cardiac surgery often necessary ....... Presence of congestive failure .........
Diabetes mellitus, narcotic addiction, alcoholism, cancer Hypertension, coronary artery disease, rheumatic heart disease
Fungi, anaerobes, staphylococci Ring abscess, myocardial abscess Streptococcus faecalis, penicillin-resistant, GNR anaerobes, fungi, Q-fever Aminoglycosides, amphotericin B Anaerobic and aerobic GNR, fungi, Q-fever
GNR = Gram-negative rods
122
AUGUST 1976
*
125
*
2
INFECTIOUS DISEASE EMERGENCIES-PART 11
be effective. In patients allergic to penicillin, a combination of vancomycin and gentamicin could be substituted with similar salutory effects. In anaerobic bacterial endocarditis in which the organisms are sensitive to penicillin, cures have been achieved with this drug.24'45 However, if the organism is resistant to penicillin, such as Bacteroides fragilis, or if a patient is truly allergic to penicillin, bacteriostatic agents such as clindamycin or chloramphenicol would have to be used. The success with these agents has been variable. 24,45 For aerobic Gram-negative bacillary endocarditis, drugs such as gentamicin, kanamycin, chloramphenicol, ampicillin, tobramycin and carbenicillin have been used alone or in various combinations according to sensitivity data.23'40 Amphotericin B remains the only useful agent for fungal endocarditis.1,16,47 The response to medical therapy of the last three forms of infective endocarditis has been disappointing, and surgical intervention frequently is required. Although in patients with endocarditis due to penicillin-sensitive organisms there is a recovery rate of 75 to 95 percent, for those in whom other types of organisms are present there is much higher mortality (see Table 11-4). This ranges from 30 to 40 percent mortality for Staphylococcus aureus, true enterococcal, penicillin-resistant anaerobic Gram-negative rod and prosthetic valve endocarditis (of all bacterial causes) to about 90 percent mortality for fungal endocarditis reported from previous series. However, a recent report of 11 patients with Candida endocarditis yielded much higher survival rates than have previously been cited.264748 In this study, early diagnosis and surgical intervention (within 48 hours of confirmation of the diagnosis) plus vigorous intraoperative and prolonged, postoperative therapy with amphotericin B, resulted in eight cures. The somewhat lower mortality rates in recent series of staphylococcal endocarditis' 14"16'20 reflect the increasing proportion of heroin addicts with this disease and the frequent occurrence of tricuspid involvement in such patients. The addict population tends to have reasonably good nutritional status without significant medical problems before endocarditis develops,'4 and infection of the tricuspid valve carries a better prognosis than endocarditis of either aortic or mitral valves'4 because of the more benign hemodynamic consequences
and lack of direct access of septic emboli to more vital organs. In addition to the virulence of the organism involved,"'14 other factors tend to increase mortality in cases of infective endocarditis (see Table II-5). In older patients, for a variety of reasons, there is a higher death rate."' 4 Patients with serious underlying cardiac or systemic diseases do not fare as well as those without these conditions. In those with aortic or mitral involvement and those in whom congestive heart failure develops there is a worse prognosis."'4'49 If there is a paravalvular infection, such as a valve-ring abscess or a myocardial abscess, or if there has been peripheral embolization causing vital organ damage or metastatic abscesses, the survival rate is significantly diminished."'4'20'50 Also, if the offending organism is difficult to eradicate with presently available therapy or the therapy intrinsically has significant toxicity, as with the aminoglycosides and amphotericin B, the mortality is exceedingly high.'12",23,24,45,51,52 The principal causes of death in patients with infective endocarditis varies somewhat, depending on which valves of the heart are involved. In those with principally left'sided involvement, cardiovascular causes, mainly congestive heart failure, predominate, with neurologic complications due to central nervous system embolization of lesser importance.50 In contrast, those with rightsided infective endocarditis die usually from both generalized as well as localized infections (principally pneumonia and meningitis) and less often from congestive heart failure.'8
The Hemodynamic Basis for Atypical Physical Findings in Acute Valvular Regurgitation J. MICHAEL CRILEY, MD* and ARNOLD H. BLAUFUSS, MD:t Infective endocarditis poses two major challenges: to isolate and treat the organism quickly and effectively, and to localize and assess the hemodynamic significance of the cardiovascular lesion or lesions. Dr. Bayer has dealt with the bacteriological aspects, and these remarks will concern themselves with valvular lesions. Unlike rheumatic heart disease, infective endocarditis may create severe valvular incompetence in a short time, and as a result the impact on the patient may be quite different and the resulting clinical findings may be quite confusing. The fol*Chief, Division of Cardiology, Harbor General Hospital, Professor of Medicine, UCLA School of Medicine. tFellow, Division of Cardiology, Harbor General Hospital.
THE WESTERN JOURNAL OF MEDICINE
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INFECTIOUS DISEASE EMERGENCIES-PART 11
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Figure Il-1.-Chronic Mitral Regurgitation-Left, left atrial (LA)/ and left ventricular (LV) pressure in a 21-year-old minimally symptomatic man with a history of recurrent acute rheumatic fever. Car at The left atrial ''V'' waves (V) are prominent, and followed sequentially by a rapid 'y' descent and rapid filling wave as the large volume within the atrium is rapidly expelled into the ventricle. The phonocardiogram shows an intact first sound (I), a holosystolic murmur (sm) and a prominent third heart sound (3). The third sound results from the rapid early diastolic inflow into the ventricle. There is no S-4. and the a-rial contraction wave (a) is not prominent. Time lines -=.04 sec. Right, a low frequency phonocardiogram (upper panel) shows the third heart sound (3), while a medium frequency recording (lower panel). better shows the systolic murmur (sm) which occupies all of systole and on some cycles continues after the second sound (2). CAR-carotid pulse tracing.
lowing is a summary of our findings in a group of 16 patients with infective endocarditis studied by cardiac catheterization, phonocardiography and echocardiography at Harbor General Hospital in the past three years. Tricuspid regurgitation, in its usual setting in rheumatic heart disease (RHD), produces a left parasternal systolic murmur with inspiratory augmentation, large V waves and a pulsatile liver. Many of these findings in patients with RHD are due to the presence of pulmonary hypertension, resulting from concurrent mitral valvular disease. In acute infective endocarditis, there may be only a soft early systolic murmur (or no murmur at all) and a normal venous pressure unless septic pulmonary emboli produce significant pulmonary vascular obstruction to cause right ventricular pressure overload. Mitral regurgitation in RHD (see Figure II-1) is associated with a holosystolic apical murmur, an early diastolic gallop sound (S-3) and a volume overload to the left atrium and ventricle resulting in gradual enlargement of these two chambers over a period of time. Significant pulmonary hypertension is unusual, since the large left atrium can accept the regurgitant volume quite well. 124
AUGUST 1976 * 125 * 2
However, acute mitral regurgitation (see Figure 11-2) has a devastating impact on the relatively noncompliant left atrium, raising its pressure to 75 to 100 mm of mercury in systole. To make matters worse, the left ventricle is also limited in its ability to accept a volume load, and the response is an increase in diastolic pressure. Therefore the left atrium is subjected to double jeopardy, a high systolic volume and pressure which it cannot get rid of in diastole. The result is a mitral stenosis-like pulmonary hypertension, pulmonary congegtion and pulmonary arterial hypertension. The murmur may be mistaken for an ejection murmur, and accompanied by a presystolic gallop sound (S-4). The reason for the unusual quality of the murmur is that the noncompliant left atrium "refuses" any more regurgitant blood in late systole because its pressure rivals the end systolic left ventricular pressure. The S-4 results from the relatively large atrial systolic contribution to the filling of the noncompliant left ventricle. Aortic regurgitation may present very atypical clinical features when the lesion occurs acutely. A clinician who expects the bounding "water hammer" pulse, enlarged hyperactive left ven-
INFECTIOUS DISEASE EMERGENCIES-PART II
tricle, long decrescendo diastolic murmur and two-phase Austin Flint rumble (see Figure 11-3) may be surprised by the unusual features of acute, sudden onset aortic regurgitation. In infective endocarditis, aortic valvular destruction may occur almost instantaneously, and the left ventricle cannot adjust to the increased diastolic volume load. The noncompliant ventricle consequently exhibits a notably elevated diastolic pressure which may exceed left atrial pressure shortly after the mitral valve opens, resulting in preclosure of the mitral valve (see Figure II-4). This preclosure leads to obliteration of the first heart sound, and frequently causes a loud middiastolic murmur as the valve closes while a large
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Figure 11-2.-Acute Mitral Regurgitation-In contrast to the patient illustrated in Figure I-1, this 48-year-old man is severely symptomatic with pronounced dyspnea and orthopnea of sudden onset during a febrile illness. Findings on an x-ray film of the chest were interpreted as bilateral pneumonia, and the heart murmur was initially thought to be due to aortic stenosis because of its medium length crescendo-decrescendo character and associated fourth heart sound. Six blood cultures were positive for group D alpha streptococcus, and he was successfully treated with penicillin and streptomycin. His hemodynamic status only permitted bed-tochair activity, and cardiac catheterization was carried out for evaluation of probable ruptured chordae tendineae. He was found to have pronounced pulmonary hypertension, striking "V" waves in the left atrium of over 100 mm of mercury and pronounced elevated left ventricular end diastolic pressure (33 mm of mercury) with prominent "a" waves. The apical systolic murmur (sm) ended well before the second sound (2, dashed line) because the left atrial pressure was sufficiently high to impede late systolic regurgitation. The fourth sound -(4) resulted from a vigorous atrial contraction (a). A soft third sound (3) was recorded, but not easily heard. Time lines=.04 sec. Angiography showed a flail anterior mitral leaflet. Valve replacement was carried out, and the patient is
currently asymptomatic.
volume of blood is leaving the left atrium. The Austin Flint murmur always implies significant aortic regurgitation, but when confined to middiastole and associated with an attenuated or absent first heart sound, it is indicative of very severe disease. The rapid elevation of left ventricular diastolic pressure may abbreviate the aortic regurgitant murmur as well as artificially support the aortic diastolic pressure, and consequently attenuate two valuable signs of aortic regurgitation.
Echocardiography Echocardiography may be extremely helpful in identifying those patients described above with endocarditis and acute mitral insufficiency. Instead of a thickened and often restricted anterior mitral leaflet as usually seen in rheumatic mitral insufficiency (see Figure 11-5), the anterior mitral leaflet in endocarditic mitral regurgitation will be thin and delicate with increased excursion (see Figure 11-6). When rupture of chordae tendineae occurs, the anterior leaflet excursion may be notably exaggerated. In addition, vibrating echoes continuous with the anterior mitral leaflet may identify mitral valve vegetations. It should be noted that similar findings are seen on the tricuspid valve and should be looked for in patients in whom right-sided infective endocarditis is suspected. Similarly, echocardiography can be extremely helpful in assessing the impact of aortic regurgitation (see Figures 11-7, 11-8, 11-9). The presence of the triad of fluttering of the anterior mitral valve preclosure, and large excursions of the left ventricular walls, is diagnostic of severe valvular incompetence and indicative of a poor outcome without surgical intervention. Occasionally, vibrating echoes in the aortic root at the level of the aortic valve may identify vegetations on the cusps. In addition vibrating echoes in the left ventricular outflow tract may suggest the presence of aortic cusp vegetations with prolapse into the left ventricular outflow tract (see Figure 11-8). The ventricular dimensions and hyperkinesis of the septum and posterior left ventricular wall are indistinguishable in acute severe mitral and aortic insufficiency, as both present a sudden volume overload to the left ventricle. Particularly noteworthy in the presence of severe valvular incompetence is early diastolic diastasis or flattening of the left side of the interventricular septum and left ventricular posterior wall (see Figure II9) as the ventricle reaches maximum compliance THE WESTERN JOURNAL OF MEDICINE
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INFECTIOUS DISEASE EMERGENCIES-PART II
ing diaphragmatic pleura it is not uncommon for the pain to be referred to the left supraclavicular area. It may have the distinction of being intensified by swallowing due to involvement of the esophagus. Rarely the pain is throbbing and synchronous with the heart beat. The primary feature noted on physical examination of patients with acute pericarditis is the presence of a pericardial friction rub. Typically the rub is triphasic, consisting of a presystolic component corresponding to atrial systole, a systolic component and an early diastolic component. Fever is common, as is tachycardia. If the pericarditis is associated with a significant effusion, the friction rub may be obliterated with the presence, then, of an increased area of cardiac dullness, muffled heart sounds, cyanosis (occasionally) and a paradoxical pulse. The presence of pulsus paradoxus indicates a significant pericardial effusion. Physical findings in a patient with pericardial tamponade are dependent on the hemodynamic deficits present. Neck vein distention is prominent with a rapid x descent in the jugular venous pulse. The y descent is not prominent as is seen in constrictive pericarditis.53 Tachycardia is usually present to maintain cardiac output and as the stage of tamponade is approached there is a drop in pulse pressure. A complete discussion of the clinical, electrocardiographic, radiologic and pathophysiologic manifestations of pericarditis, pericardial effusion and tamponade can be found in a symposium previously published in this
in early diastole because of the large volume overload. Small posterior pericardial effusions may also be seen (see Figure 11-9), but large effusions are distinctly rare in infective endocarditis.
Summary and Conclusions The confusing physical findings presented by patients with infective endocarditis should not mislead a physician into assuming that there is extensive myocardial damage and not severe valvular regurgitation because of the paucity of murmurs, loud gallop sounds and soft or absent first sound. Echocardiograms have been invaluable in assessing valve -function and provide an accurate noninvasive method for serially studying the size and performance of the left ventricle. It is hoped that this treatise on the hemodynamic basis for atypical findings will stimulate a more aggressive use of noninvasive instruments, including the stethoscope, in the management of these desperately ill patients. DR. OILL: Before Dr. Bayer discusses infectious pericarditis and myocarditis, I will briefly review the clinical signs and symptoms associated with these diseases. In patients with infectious pericarditis there may be evidence of acute pericarditis alone or significant pericardial effusion and tamponade may be noted in addition. In acute pericarditis, precordial pain is common-sometimes mimicking a myocardial infarction-and is frequently affected by respiratory movements, cough and position. Because of inflammation of the adjoin-
journal.54 The typical clinical features of myocarditis are -200-
Figure 11-3.
-
Chronic Aortic
_
__
__
_
__
_
Regurgitation - A 30-year-old woman with childhood rheu2 APEX matic fever was minimaly2RC symptomatic, but was noted to have progressive cardiac enem l i cLaCS largement on serial x-ray studies of the chest. The bounding -100arterial pulses are shown in the aortic (Ao) pressure of 175/40. The left ventricular end / diastolic pressure is minimally elevated (18 mm of mercury). A loud ejection systolic murmur (sm) due to high flow was heard in the aortic area (left panel, sm), and a high-pitched early diastolic murmur of aor--___________________-----__ tic regurgitation (edm) was heard at both sides of the sternum. At the apex (right panel) a two component Austin Flint murmur was heard, indicated forward flow across a functionally restricted mitral orifice throughout all of diastole.
1 26
AUGUST 1976 * 125 * 2
INFECTIOUS DISEASE EMERGENCIES-PART 11
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