- Email: [email protected]
Left ventricular hypertrophy in normotensive cocaine users
Volume 125, Number 5, Part 1 American Heart Journal
Om et al.
diography, and pulmonary artery catheterization. HIV infection is increasingly recognized as an important cofactor in the development of dilated cardiomyopathy.5 However, in the majority of cases the primary cause remains obscure. Rarely, responsible nutritional deficiencies, metabolic disorders, infectious and noninfectious myocarditis, infiltrative processes, and toxins are identified. In this patient foscarnet toxicity appears to be the most likely explanation for cardiac dysfunction given the absence of other causes of depressed cardiac function and the temporal relation between foscarnet therapy and the development and resolution of symptoms and signs. The mechanism by which foscarnet could cause cardiac toxicity is unclear. Recently the antiretroviral agents zidovudine, 2’,3’-dideoxyinosine and 2’,3’-dideoxycytidine were reported to be associated with the development of cardiomyopathy in HIV-infected patients.6 However, our patient was treated with two of these agents without the development of cardiac dysfunction. Thus, although these agents have in common with foscarnet the ability to inhibit DNA polymerases, including reverse transcriptase, the cardiac toxicity of these agents is unlikely to involve their ability to inhibit these enzymes. Regardless of the exact mechanism of toxicity, physicians should be aware that foscarnet may cause acute, severe, reversible cardiac dysfunction in susceptible patients. REFERENCES
1. Jacobson MA, Mills J. Serious cytomegalovirus disease in the acquired immunodeficiency syndrome (AIDS). Clinical findings, diagnosis, and treatment. Ann Intern Med 1988:108:58594. 2. Oberg B. Antiviral effects of phosphonoformate. Pharmacol Ther 1983;19:387-415. 3. Palestine Ag, Polis MA, De Smet MD, Baird BF, Falloon J, Kovacs JA, Davey RT, Zurlo JJ, Zunich KM, Davis M, Hubbard L, Brothers R, Ferris FL, Chew E, Davis JL, Rubin BI, Mellow SD, Metcalf JA, Manischewitz J, Minor JR, Nussenblatt RB, Masur H, Lane HC. A randomized controlled trial of foscarnet in the treatment of cytomegalovirus retinitis in patients with AIDS. Ann Intern Med 1991;115:665-73. 4. Studies of ocular complications of AIDS research group, AIDS clinical trials group. Mortality in patients with the acquired immunodeficiency syndrome treated with either foscarnet or ganciclovir for cytomegalovirus retinitis. N Engl J Med 1992;326:213-20. 5.
Kaul S, Fishbein MC, Siegel RJ. Cardiac manifestations of acquired immune deficiency syndrome: a 1991 update. AM
6.
Herskowitz A, Willoughby S, Baughman KL, Schulman SP, Bartlett JD. Cardiomyopathy associated with antiretroviral therapy in patients with HIV infection: a report of six cases. Ann Intern Med 1992;116:311-3.
HEART
J 1991;122:535-44.
Left ventricular hypertrophy in normotensive cocaine users Anil Om, MD, Samer Ellahham, MD, George W. Vetrovec, MD, Catherine Guard, Steven Reese, BS, and J. V. Nixon, MD Richmond, Vu.
RDCS,
lated cardiovascular deaths, as a consequence of myocardial infarction, ventricular tachyarrhythmias, or aortic dissection.’ Coronary spasm, thrombosis, and higher than expected coronary artery disease could be the causes of myocardial infarction in cocaine users. However, the mechanism of cocaine-induced tachyarrhythmias in the absence of myocardial infarction is not well understood. Cocaine has been shown to shorten the ventricular refractory period2 that could predispose to tachyarrhythmias. Left ventricular hypertrophy (LVH) is known to be an independent risk factor predisposing to ventricular arrhythmias.3,4 Cocaine use produces a hyperadrenergic state leading to episodes of transient. systemic hypertention. The present study was undertaken to determine whether or not such episodes of hypertension predisposes normotensive cocaine users to develop LVH. Methods. The echocardiograms of 58 cocaine users (35 men and 23 women) without any history of sustained systemic hypertension, echocardiographic presence of valvular abnormalities, history of human immunodeficiency virus infection, or excessive physical work were evaluated for left ventricular chamber size, function, and mass. Of 35 men, 28 (80 00 ) were black and seven (20 “‘D) were white; of 23 women, 15 (65%) were black and eight (35%) were white. Indications for echocardiograms were: (1) to rule out endocarditis (n = 50), (2) to evaluate left ventricular function (n = 6), and (3) to assess those with a history of chest pain (n = 2). All patients had a history of alcohol intake. The quantity, frequency, and the duration of alcohol and cocaine intake could not be reliably obtained because of the inconsistencies in the history provided by the patients. The predominant route of cocaine administration was intravenous in 48, smoking or sniffing in five, and multiple routes in five patients. Healthy hospital volunteers without any history of systemic hypertension, recreational drug use, excessive dynamic or isometric exercise training, or cardiovascular disease underwent echocardiographic evaluation for the assessment of left ventricular chamber size, function, and mass. There were 30 men (23 black and 7 white) and 18 women (12 black and 6 white) enrolled as controls. Echocardiography was performed with an ultrasound instrument (model No. 7702A, Hewlett-Packard, Inc., Andover, Mass.; or model MK-600, Advanced Technical Laboratories, Seattle, Wash.). Two-dimensional echocardiograms were obtained in parasternal long- and short-axis views and in apical two- and four-chamber views. Measurements were made from the two-dimensional parasternal long-axis view by the Penn method, and left ventricular mass (LVM) was calculated by the method of Devereux et a1.5 LVH was defined as LVM index of >125 gm/m* for men and >llO gm/m2 for women. Because of extremes of values and unequal variance between the
From the Division of Cardiology, Department of Internal Medicine, Medical College of Virginia, Virginia Commonwealth University. Reprint requests: Anil Om, MD, Box 281-MCV Station, Medical College of Virginia, Richmond, VA 23298. AM HEART
In recent years the number of cocaine users has significantly increased. This has led to an increase in cocaine-re-
1441
J 1993;125:1441-1443.
Copyright i 1993 by Mosby-Year Book, Inc. 0002.8703/93/$1.00 + .I0 4/4/44897
On et al.
1442
American
MEN CONTROLS
WOMEN PATIENTS
CONTROLS n-18
I. Age and left ventricular mass(LVM) index of cu Caineusersand controls -___..-Table
PATIENTS n = 23
310 300
.
220
May 1993 Heart Journal
Men Controls
No.
Mean a.+ br)
30
30 t 6
Mean LVM index 83 It 23 *
200
.
180
.
Controls
:
: . .
160
:
Cocaine users
: .
l .
. . .
F !
Y I
...
.
t
. .
40
. ~p=0.0014
30 ~fr 8
82 t 14
23
34 -+ 8.7
s
110 t 53
$p = 0.04.
:
.;
60
18
i
112 f 41
tp = 0.001. Sp=NS.
:
80
33 k 6.6
f
.
.. !T
35
*p = 0.04.
i .. I
1
100
Cocaineusers Women
+pso.o37-
-I
20
Fig. 1. Distribution of left ventricular mass(LVM)
indi-
ces of cocaine usersand controls.
groups, we used the Wilcoxon two-sample rank sum test. Mean values were given as + 1 standard deviation. Results. Mean values for LVM index were significantly higher for both men and women cocaine users than for controls (men 112 & 41 vs 83 f 23 gm/m2, p = 0.001; women 110 + 53 vs 82 f 14 gm/m2, p = 0.037 (Table I). Although there wasconsiderableoverlap, the frequency of LVH washigher in cocaineusersthan in controls (Fig. 1). There wasno correlation between the route of cocaineadministration and the presence of LVH. Twelve of 48 patients (25%) with predominant intravenous cocaineuse, and 2 of 10patients (20%) with sniffing and multiple routes of cocaine use had the presenceof LVH. Comments. Our study revealsthat normotensivecocaine userswithout any cardiovascular risk factor for LVH may be predisposedto LVH despite their young age. Cocaine blocksthe reuptake of norepinephrine and dopamineat the presynaptic receptor site and this hyperadrenergic state leads to generalized peripheral vasoconstriction and hypertension. The most likely etiology of LVH in normotensivecocaineusersis the transient elevation of systolic blood pressureafter cocaineuse.A direct correlation betweenthe presenceof LVH and the elevation of systolic blood pressure has been made by others. Gottdiener et a1.6demonstrated the presenceof LVH in normotensive men with ex-
aggerated systolic blood pressure responseto exercise. Similarly, an associationbetween LVH and systolic blood pressureresponseunder a stressfulsituation or exercisehas been noted in normotensive7and hypertensive individuals.svgThe other possiblemechanismof LVH in cocaine userscould bethe direct stimulation of myocardialcu-adrenergic receptors. Such receptor stimulation hasbeen shown to induce hypertrophy of cardiac myocytes in vitro.” Alcohol intake in excessof 210ml/week hasbeenshownto cause LVH in men in the Framingham study.” Cocaine users frequently alsousealcohol.All of our patients had a history of alcohol intake; however,its amount and frequency could not be reliably obtained. Therefore the contribution of alcohol to the induction of LVH in our patients could not be delineated. We could not establish a correlation between the dose,frequency, and duration of cocaineuseand LVH becauseof lack of reliable history, which is commonin inner city drug users.12 The presenceof LVH in cocaine users has also been demonstrated in autopsy studies. Virmani et all3 found 8 of 40 patients with cocaine-relateddeath to have increased LVM. Similar findings were noted by Dressleret a1.,14who found heart weights of >450 gm in 11 of 22 (50%) cocaine addicts. Becausethese were autopsy findings, a history of systemic hypertension could not be excluded in these studies.Recently Brickner et a1.l”alsodemonstrated a significant increasein echocardiographicLVM index and wall thicknessin 30 cocaineuserscomparedwith their controls. Patients enrolled in their study, however, were from an inpatient drug rehabilitation unit and therefore could have been using cocaine frequently and in higher doses.The LVM index of 112 & 41 gm/m2 for men in our study, despite their young ageand lack of risk factors for LVH, suggestsan increasein LVM index compared with controls. One of our female patients had an LVM index of 311gm/ m2. She had a history of cocaineusefor more than 4 years and on many admissionswas found to be severely hypertensive after cocaine use. Although the mean age of men cocaine userswas higher (33 + 6.6 years) compared with, that of controls (30 t 5 years), we do not think this 3-year difference could have accounted for the increasedLVM in-
Volume 125, Number 5, Part 1 American HearI Journal
Lee, Topol, and Stewart
dex in cocaine users. In conclusion, our study shows that despite their young age, normotensive cocaine users may be at higher risk of developing LVH that may predispose these patients to myocardial ischemia, infarction, tachyarrhythmias, or sudden death. REFERENCES
1. Isner JM, Mark Ester NA III, Thompson PD, Costanzo-Nordin MR, Subramanium R, Miller G, Kastsas G, Sweeney K, Sturner WQ. Acute cardiac events temporarily related to cocaine abuse. N Engl J Med 1986;315:1438-43. 2. Inoue H, Zipes D. Cocaine-induced supersensitivity and arrhythmogenesis. J Am Co11 Cardiol 1988;11:867-74. 3. Levv D. Anderson KM. Savage DD. Balkus SA. Kannel WB. Castehi WP. Risk of ventricular arrhythmias in’left ventricu: lar hypertrophy: the Framingham Heart Study. Am J Cardiol 1987;60:560-5. 4. McLenadian JM, Henderson E, Morris KI, Dargie HJ. Ventricular arrhythmias in patients with hypertensive left ventricular hypertrophy. N Engl J Med 1987;317:787-92. 5. Devereux RB, Alonso DR, Lutas EM, Gottlieb GJ, Campo E, Sachs I, Reichek N. Echocardiographic assessment of left ventricular hypertrophy: comparison to necropsy findings. Am J Cardiol 1986;57:450-8. 6. Gottdiener JS, Brown J, Zoltick J, Fletcher RD. Left ventricular hypertrophy in men with normal blood pressure: relation to exaggerated blood pressure response to exercise. Ann Intern Med 1990;112:161-6. 7. Lauer MS, Anderson KM, Levy D. Influence of contemporary versus 30 year blood pressure levels on left ventricular mass and geometry: the Framingham Heart Study. J Am Co11Cardiol 1991;18:1287-94. 8. Devereux RB, Pickering TG, Harshfield GA. Left ventricular hypertrophy in patients with hypertension: importance of blood pressure response to regularly recurring stress. Circulation 1983;68:470-6. 9. Ren JF, Hakki AH, Kotler MN, Iskandrian AS. Exercise systolic blood pressure: a powerful determinant of increased left ventricular mass in patients with hypertension. J Am Co11 Cardiol 1985;5:1224-31. 10. Simpson P. Stimulation of hypertrophy of cultured neonatal rat heart cells through alpha-l adrenergic receptor and induction of beating through an alpha-l and beta-l adrenergic receptor interaction. Circ Res 1985;56:884-94. 11. Manolio TA, Levy D, Garrison RJ, Castelli WP, Kannel WB. Relation of alcohol intake to left ventricular mass: the Framingham Study. J Am Co11 Cardiol 1991;17:717-21. 12. McNaenv SE. Parker RM. Hiah nrevalance of recent cocaine user and the unreliability of patient self-respect in an inner city walk-in clinic. JAMA 1992;167:1106-8. 13. Virmani R, Robinowitz M, Smialek JE, Smyth DF. Cardiovascular effects of cocaine: an autopsy study of 40 patients. AM -”
-
-
HEARTJ 1988;115:1068-76. 14. Dressier FA, Malekzadeh S, Roberts WC. Quantitative anal-
ysis of amounts of coronary arterial narrowing in cocaine addicts. Am J Cardiol 1990;65:303-8. 15. Brickner ME, Willard JE, Eichhorn EJ, Black J, Grayburn PA. Left ventricular hypertrophy associated with chronic cocaine abuse. Circulation 1991;84:1130-5.
Atypical presentation of papillary fibroelastoma mimicking multiple vegetations in suspected subacute bacterial endocarditis
Cardiac papillary fibroelastomas are rare benign tumors that in the past have usually been found incidentally at cardiacsurgery and at autopsy. Fibroelastomasare increasingly detected with two-dimensionalechocardiography,by visualizing a singlemobile density attached to a semilunar or atrioventricular valve in an individual without clinical features of infection. We present a caseof multiple intracardiac massesin a womanwith fever, who wastreated with a full courseof antibiotics for endocarditis. This caseillustrates an atypical appearanceinvolving multiple papillary fibroelastomasthat wasinitially referred to The Cleveland Clinic Hospital for managementof presumed treatmentrefractory endocarditis. This 57-year-old woman had a past history notable for hypertrophic obstructive cardiomyopathy, for which she had undergoneseptal myectomy 15 years previously. Preoperative M-mode echocardiogramrevealed systolic anterior motion (SAM) of the mitral valve and left ventricular hypertrophy (LVH) but no mobile masses.A cardiac catheterization performed 1 year after surgery demonstrated resolution of the outflow gradient and hyperdynamic left ventricular systolic function. The ventriculogram wasunremarkable. Her present illnessbeganwith fever occurring after cystoscopy for evaluation of recurrent urinary tract infections. Despite intravenous antibiotics given for prophylaxis, shedevelopedon the sameday shakingchills and a 103’ F oral temperature. After taking ciprofloxacin for 3 days, her symptoms remained. A transthoracic echocardiogram demonstrated multiple aortic and mitral valve densitiespresumedto be bacterial vegetations. A transesophagealechocardiogram(TEE) confirmed the presence of at least sevenseparateintracardiac masseslocated at the left ventricular (LV) septum, at the LV outflow tract, on the anterior and posterior chords of the mitral valve, and several masseson the aortic valve. There was 3+ moderately severemitral regurgitation. Her urinary tract work-up revealed a cystocele and rectocele. Urine culture grew Klebsiella pneumoniae, and blood cultures showed no growth. Based on a diagnosis of culture-negative endocarditis, the patient received intravenous ampicillin and gentamicin for 6 weeks.She felt better and remained afebrile during the duration of antibiotic therapy. Two months after discharge from the hospital, the patient presentedwith recurrent fever to 103’ F and shaking chills. She wasgiven oral antibiotics for a presumptive diagnosisof urinary tract infection. Without clinical improvement, shewasreadmitted to the hospital. Urine cultures again grew KlebsieIla pneumoniae. Blood cultures showedno growth. The patient was then considered for surgery for a presumptive diagnosisof treatment-resistant
From the Department of Cardiology, The Cleveland Clinic Foundation. Reprint requests: Dr. William J. Stewart, Desk F15, Department of Cardiology, The Cleveland Clinic Foundation, 9500 Euclid Ave., Cleveland, OH 44195. AM HEART
Kamthorn S. Lee, MD, Eric J. Topol, MD, and William J. Stewart, MD Cleveland, Ohio
g443
Copyright
J 1993;125:1443-1445.
@ 1993 by Mosby-Year
0002.8703/93/$1.00
-t .lO
4/4/44894
Book, Inc.
Om et al.
diography, and pulmonary artery catheterization. HIV infection is increasingly recognized as an important cofactor in the development of dilated cardiomyopathy.5 However, in the majority of cases the primary cause remains obscure. Rarely, responsible nutritional deficiencies, metabolic disorders, infectious and noninfectious myocarditis, infiltrative processes, and toxins are identified. In this patient foscarnet toxicity appears to be the most likely explanation for cardiac dysfunction given the absence of other causes of depressed cardiac function and the temporal relation between foscarnet therapy and the development and resolution of symptoms and signs. The mechanism by which foscarnet could cause cardiac toxicity is unclear. Recently the antiretroviral agents zidovudine, 2’,3’-dideoxyinosine and 2’,3’-dideoxycytidine were reported to be associated with the development of cardiomyopathy in HIV-infected patients.6 However, our patient was treated with two of these agents without the development of cardiac dysfunction. Thus, although these agents have in common with foscarnet the ability to inhibit DNA polymerases, including reverse transcriptase, the cardiac toxicity of these agents is unlikely to involve their ability to inhibit these enzymes. Regardless of the exact mechanism of toxicity, physicians should be aware that foscarnet may cause acute, severe, reversible cardiac dysfunction in susceptible patients. REFERENCES
1. Jacobson MA, Mills J. Serious cytomegalovirus disease in the acquired immunodeficiency syndrome (AIDS). Clinical findings, diagnosis, and treatment. Ann Intern Med 1988:108:58594. 2. Oberg B. Antiviral effects of phosphonoformate. Pharmacol Ther 1983;19:387-415. 3. Palestine Ag, Polis MA, De Smet MD, Baird BF, Falloon J, Kovacs JA, Davey RT, Zurlo JJ, Zunich KM, Davis M, Hubbard L, Brothers R, Ferris FL, Chew E, Davis JL, Rubin BI, Mellow SD, Metcalf JA, Manischewitz J, Minor JR, Nussenblatt RB, Masur H, Lane HC. A randomized controlled trial of foscarnet in the treatment of cytomegalovirus retinitis in patients with AIDS. Ann Intern Med 1991;115:665-73. 4. Studies of ocular complications of AIDS research group, AIDS clinical trials group. Mortality in patients with the acquired immunodeficiency syndrome treated with either foscarnet or ganciclovir for cytomegalovirus retinitis. N Engl J Med 1992;326:213-20. 5.
Kaul S, Fishbein MC, Siegel RJ. Cardiac manifestations of acquired immune deficiency syndrome: a 1991 update. AM
6.
Herskowitz A, Willoughby S, Baughman KL, Schulman SP, Bartlett JD. Cardiomyopathy associated with antiretroviral therapy in patients with HIV infection: a report of six cases. Ann Intern Med 1992;116:311-3.
HEART
J 1991;122:535-44.
Left ventricular hypertrophy in normotensive cocaine users Anil Om, MD, Samer Ellahham, MD, George W. Vetrovec, MD, Catherine Guard, Steven Reese, BS, and J. V. Nixon, MD Richmond, Vu.
RDCS,
lated cardiovascular deaths, as a consequence of myocardial infarction, ventricular tachyarrhythmias, or aortic dissection.’ Coronary spasm, thrombosis, and higher than expected coronary artery disease could be the causes of myocardial infarction in cocaine users. However, the mechanism of cocaine-induced tachyarrhythmias in the absence of myocardial infarction is not well understood. Cocaine has been shown to shorten the ventricular refractory period2 that could predispose to tachyarrhythmias. Left ventricular hypertrophy (LVH) is known to be an independent risk factor predisposing to ventricular arrhythmias.3,4 Cocaine use produces a hyperadrenergic state leading to episodes of transient. systemic hypertention. The present study was undertaken to determine whether or not such episodes of hypertension predisposes normotensive cocaine users to develop LVH. Methods. The echocardiograms of 58 cocaine users (35 men and 23 women) without any history of sustained systemic hypertension, echocardiographic presence of valvular abnormalities, history of human immunodeficiency virus infection, or excessive physical work were evaluated for left ventricular chamber size, function, and mass. Of 35 men, 28 (80 00 ) were black and seven (20 “‘D) were white; of 23 women, 15 (65%) were black and eight (35%) were white. Indications for echocardiograms were: (1) to rule out endocarditis (n = 50), (2) to evaluate left ventricular function (n = 6), and (3) to assess those with a history of chest pain (n = 2). All patients had a history of alcohol intake. The quantity, frequency, and the duration of alcohol and cocaine intake could not be reliably obtained because of the inconsistencies in the history provided by the patients. The predominant route of cocaine administration was intravenous in 48, smoking or sniffing in five, and multiple routes in five patients. Healthy hospital volunteers without any history of systemic hypertension, recreational drug use, excessive dynamic or isometric exercise training, or cardiovascular disease underwent echocardiographic evaluation for the assessment of left ventricular chamber size, function, and mass. There were 30 men (23 black and 7 white) and 18 women (12 black and 6 white) enrolled as controls. Echocardiography was performed with an ultrasound instrument (model No. 7702A, Hewlett-Packard, Inc., Andover, Mass.; or model MK-600, Advanced Technical Laboratories, Seattle, Wash.). Two-dimensional echocardiograms were obtained in parasternal long- and short-axis views and in apical two- and four-chamber views. Measurements were made from the two-dimensional parasternal long-axis view by the Penn method, and left ventricular mass (LVM) was calculated by the method of Devereux et a1.5 LVH was defined as LVM index of >125 gm/m* for men and >llO gm/m2 for women. Because of extremes of values and unequal variance between the
From the Division of Cardiology, Department of Internal Medicine, Medical College of Virginia, Virginia Commonwealth University. Reprint requests: Anil Om, MD, Box 281-MCV Station, Medical College of Virginia, Richmond, VA 23298. AM HEART
In recent years the number of cocaine users has significantly increased. This has led to an increase in cocaine-re-
1441
J 1993;125:1441-1443.
Copyright i 1993 by Mosby-Year Book, Inc. 0002.8703/93/$1.00 + .I0 4/4/44897
On et al.
1442
American
MEN CONTROLS
WOMEN PATIENTS
CONTROLS n-18
I. Age and left ventricular mass(LVM) index of cu Caineusersand controls -___..-Table
PATIENTS n = 23
310 300
.
220
May 1993 Heart Journal
Men Controls
No.
Mean a.+ br)
30
30 t 6
Mean LVM index 83 It 23 *
200
.
180
.
Controls
:
: . .
160
:
Cocaine users
: .
l .
. . .
F !
Y I
...
.
t
. .
40
. ~p=0.0014
30 ~fr 8
82 t 14
23
34 -+ 8.7
s
110 t 53
$p = 0.04.
:
.;
60
18
i
112 f 41
tp = 0.001. Sp=NS.
:
80
33 k 6.6
f
.
.. !T
35
*p = 0.04.
i .. I
1
100
Cocaineusers Women
+pso.o37-
-I
20
Fig. 1. Distribution of left ventricular mass(LVM)
indi-
ces of cocaine usersand controls.
groups, we used the Wilcoxon two-sample rank sum test. Mean values were given as + 1 standard deviation. Results. Mean values for LVM index were significantly higher for both men and women cocaine users than for controls (men 112 & 41 vs 83 f 23 gm/m2, p = 0.001; women 110 + 53 vs 82 f 14 gm/m2, p = 0.037 (Table I). Although there wasconsiderableoverlap, the frequency of LVH washigher in cocaineusersthan in controls (Fig. 1). There wasno correlation between the route of cocaineadministration and the presence of LVH. Twelve of 48 patients (25%) with predominant intravenous cocaineuse, and 2 of 10patients (20%) with sniffing and multiple routes of cocaine use had the presenceof LVH. Comments. Our study revealsthat normotensivecocaine userswithout any cardiovascular risk factor for LVH may be predisposedto LVH despite their young age. Cocaine blocksthe reuptake of norepinephrine and dopamineat the presynaptic receptor site and this hyperadrenergic state leads to generalized peripheral vasoconstriction and hypertension. The most likely etiology of LVH in normotensivecocaineusersis the transient elevation of systolic blood pressureafter cocaineuse.A direct correlation betweenthe presenceof LVH and the elevation of systolic blood pressure has been made by others. Gottdiener et a1.6demonstrated the presenceof LVH in normotensive men with ex-
aggerated systolic blood pressure responseto exercise. Similarly, an associationbetween LVH and systolic blood pressureresponseunder a stressfulsituation or exercisehas been noted in normotensive7and hypertensive individuals.svgThe other possiblemechanismof LVH in cocaine userscould bethe direct stimulation of myocardialcu-adrenergic receptors. Such receptor stimulation hasbeen shown to induce hypertrophy of cardiac myocytes in vitro.” Alcohol intake in excessof 210ml/week hasbeenshownto cause LVH in men in the Framingham study.” Cocaine users frequently alsousealcohol.All of our patients had a history of alcohol intake; however,its amount and frequency could not be reliably obtained. Therefore the contribution of alcohol to the induction of LVH in our patients could not be delineated. We could not establish a correlation between the dose,frequency, and duration of cocaineuseand LVH becauseof lack of reliable history, which is commonin inner city drug users.12 The presenceof LVH in cocaine users has also been demonstrated in autopsy studies. Virmani et all3 found 8 of 40 patients with cocaine-relateddeath to have increased LVM. Similar findings were noted by Dressleret a1.,14who found heart weights of >450 gm in 11 of 22 (50%) cocaine addicts. Becausethese were autopsy findings, a history of systemic hypertension could not be excluded in these studies.Recently Brickner et a1.l”alsodemonstrated a significant increasein echocardiographicLVM index and wall thicknessin 30 cocaineuserscomparedwith their controls. Patients enrolled in their study, however, were from an inpatient drug rehabilitation unit and therefore could have been using cocaine frequently and in higher doses.The LVM index of 112 & 41 gm/m2 for men in our study, despite their young ageand lack of risk factors for LVH, suggestsan increasein LVM index compared with controls. One of our female patients had an LVM index of 311gm/ m2. She had a history of cocaineusefor more than 4 years and on many admissionswas found to be severely hypertensive after cocaine use. Although the mean age of men cocaine userswas higher (33 + 6.6 years) compared with, that of controls (30 t 5 years), we do not think this 3-year difference could have accounted for the increasedLVM in-
Volume 125, Number 5, Part 1 American HearI Journal
Lee, Topol, and Stewart
dex in cocaine users. In conclusion, our study shows that despite their young age, normotensive cocaine users may be at higher risk of developing LVH that may predispose these patients to myocardial ischemia, infarction, tachyarrhythmias, or sudden death. REFERENCES
1. Isner JM, Mark Ester NA III, Thompson PD, Costanzo-Nordin MR, Subramanium R, Miller G, Kastsas G, Sweeney K, Sturner WQ. Acute cardiac events temporarily related to cocaine abuse. N Engl J Med 1986;315:1438-43. 2. Inoue H, Zipes D. Cocaine-induced supersensitivity and arrhythmogenesis. J Am Co11 Cardiol 1988;11:867-74. 3. Levv D. Anderson KM. Savage DD. Balkus SA. Kannel WB. Castehi WP. Risk of ventricular arrhythmias in’left ventricu: lar hypertrophy: the Framingham Heart Study. Am J Cardiol 1987;60:560-5. 4. McLenadian JM, Henderson E, Morris KI, Dargie HJ. Ventricular arrhythmias in patients with hypertensive left ventricular hypertrophy. N Engl J Med 1987;317:787-92. 5. Devereux RB, Alonso DR, Lutas EM, Gottlieb GJ, Campo E, Sachs I, Reichek N. Echocardiographic assessment of left ventricular hypertrophy: comparison to necropsy findings. Am J Cardiol 1986;57:450-8. 6. Gottdiener JS, Brown J, Zoltick J, Fletcher RD. Left ventricular hypertrophy in men with normal blood pressure: relation to exaggerated blood pressure response to exercise. Ann Intern Med 1990;112:161-6. 7. Lauer MS, Anderson KM, Levy D. Influence of contemporary versus 30 year blood pressure levels on left ventricular mass and geometry: the Framingham Heart Study. J Am Co11Cardiol 1991;18:1287-94. 8. Devereux RB, Pickering TG, Harshfield GA. Left ventricular hypertrophy in patients with hypertension: importance of blood pressure response to regularly recurring stress. Circulation 1983;68:470-6. 9. Ren JF, Hakki AH, Kotler MN, Iskandrian AS. Exercise systolic blood pressure: a powerful determinant of increased left ventricular mass in patients with hypertension. J Am Co11 Cardiol 1985;5:1224-31. 10. Simpson P. Stimulation of hypertrophy of cultured neonatal rat heart cells through alpha-l adrenergic receptor and induction of beating through an alpha-l and beta-l adrenergic receptor interaction. Circ Res 1985;56:884-94. 11. Manolio TA, Levy D, Garrison RJ, Castelli WP, Kannel WB. Relation of alcohol intake to left ventricular mass: the Framingham Study. J Am Co11 Cardiol 1991;17:717-21. 12. McNaenv SE. Parker RM. Hiah nrevalance of recent cocaine user and the unreliability of patient self-respect in an inner city walk-in clinic. JAMA 1992;167:1106-8. 13. Virmani R, Robinowitz M, Smialek JE, Smyth DF. Cardiovascular effects of cocaine: an autopsy study of 40 patients. AM -”
-
-
HEARTJ 1988;115:1068-76. 14. Dressier FA, Malekzadeh S, Roberts WC. Quantitative anal-
ysis of amounts of coronary arterial narrowing in cocaine addicts. Am J Cardiol 1990;65:303-8. 15. Brickner ME, Willard JE, Eichhorn EJ, Black J, Grayburn PA. Left ventricular hypertrophy associated with chronic cocaine abuse. Circulation 1991;84:1130-5.
Atypical presentation of papillary fibroelastoma mimicking multiple vegetations in suspected subacute bacterial endocarditis
Cardiac papillary fibroelastomas are rare benign tumors that in the past have usually been found incidentally at cardiacsurgery and at autopsy. Fibroelastomasare increasingly detected with two-dimensionalechocardiography,by visualizing a singlemobile density attached to a semilunar or atrioventricular valve in an individual without clinical features of infection. We present a caseof multiple intracardiac massesin a womanwith fever, who wastreated with a full courseof antibiotics for endocarditis. This caseillustrates an atypical appearanceinvolving multiple papillary fibroelastomasthat wasinitially referred to The Cleveland Clinic Hospital for managementof presumed treatmentrefractory endocarditis. This 57-year-old woman had a past history notable for hypertrophic obstructive cardiomyopathy, for which she had undergoneseptal myectomy 15 years previously. Preoperative M-mode echocardiogramrevealed systolic anterior motion (SAM) of the mitral valve and left ventricular hypertrophy (LVH) but no mobile masses.A cardiac catheterization performed 1 year after surgery demonstrated resolution of the outflow gradient and hyperdynamic left ventricular systolic function. The ventriculogram wasunremarkable. Her present illnessbeganwith fever occurring after cystoscopy for evaluation of recurrent urinary tract infections. Despite intravenous antibiotics given for prophylaxis, shedevelopedon the sameday shakingchills and a 103’ F oral temperature. After taking ciprofloxacin for 3 days, her symptoms remained. A transthoracic echocardiogram demonstrated multiple aortic and mitral valve densitiespresumedto be bacterial vegetations. A transesophagealechocardiogram(TEE) confirmed the presence of at least sevenseparateintracardiac masseslocated at the left ventricular (LV) septum, at the LV outflow tract, on the anterior and posterior chords of the mitral valve, and several masseson the aortic valve. There was 3+ moderately severemitral regurgitation. Her urinary tract work-up revealed a cystocele and rectocele. Urine culture grew Klebsiella pneumoniae, and blood cultures showed no growth. Based on a diagnosis of culture-negative endocarditis, the patient received intravenous ampicillin and gentamicin for 6 weeks.She felt better and remained afebrile during the duration of antibiotic therapy. Two months after discharge from the hospital, the patient presentedwith recurrent fever to 103’ F and shaking chills. She wasgiven oral antibiotics for a presumptive diagnosisof urinary tract infection. Without clinical improvement, shewasreadmitted to the hospital. Urine cultures again grew KlebsieIla pneumoniae. Blood cultures showedno growth. The patient was then considered for surgery for a presumptive diagnosisof treatment-resistant
From the Department of Cardiology, The Cleveland Clinic Foundation. Reprint requests: Dr. William J. Stewart, Desk F15, Department of Cardiology, The Cleveland Clinic Foundation, 9500 Euclid Ave., Cleveland, OH 44195. AM HEART
Kamthorn S. Lee, MD, Eric J. Topol, MD, and William J. Stewart, MD Cleveland, Ohio
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