- Email: [email protected]
Inefficacy of daily single bolus dose atrial natriuretic factor in chronic congestive heart failure
1. Lipkin DP, Poolswilson PA. Measurementof cardiac output during exercise by the thermodilution and direct Fick techniquesin patientswith chronic congestive heart failure. Am .I Cardiol 1985;56:321-324. 2. Wang Y, Gutman JM, Heilbron D, Wahr D, Schiller NB. Atria1 volume in a normal adult population by two-dimensional echocardiography. Chesf 1984: 86:595-601.
2. Perry GJ, Nanda NC. Recent advancesin color flow Doppler assessmentof valvular regurgitation. Echocardiography 1987;4:503-513. 4. Cornyn JW, Massie BM, Unverferth DV, L&r CV. Hemodynamic changes after meals and placebo treatment in chronic congestive heart failure. Am J Cardiol 1986;57:238-241.
5. HiUis LD, Fiih BG, Winniford MD. Analysis of factors affecting the variability of Fick versusindicator dilution measurementsof cardiac output. Am J Cardiol 1985:56:764-768.
9. Rubin SA, SiemienczukD, Nathan MD, PrauseJ, Swan HJC. Accuracy of
cardiac output, oxygenuptake,and arteriovenousoxygendifference at rest,during exercise, and after vasodilator therapy in patients with severe, chronic heart failure. Am J Cardiol 1982;50:973-978. 7. Kashtan HI, Maitland A, Salerno TA, Lichtenstein SV, Byrick RJ. Effects of tricuspid regurgitation on thermodilution cardiac output: studies in an animal model. Can J Anaesth 1987;34:246-251. 8. Beyer J, Lamberti JJ, Replogle RL. Validity of therm&&on cardiac output determination:experimental studieswith and without pulmonary insufficiency. J Surg Res 1976;21:313-317.
9. Van Grondelle A, Ditchey RV, Groves BM, Wagner WW, ReevesJT. Thermodilution method overestimateslow cardiac output in humans.Am J Physiol 1983;245:H690-H692.
10. Venkatamaran K, De Guzman M, Hafeezkhan A, Haywood LJ. Cardiac output measurement:a comparisonof direct Fick, dye dilution and thermcdilution methodsin stable and acutely ill patients. J NatI Med Assoc 1976,68:281-284.
Inefficacy of Daily Single Bobs Dose Atrial Natriuretic in Chronic Congestive Heart Failure
Factor
Ian G. Crozier, MD, A. Mark Richards, MD, M. Gary Nicholls, MD, Eric A. Espiner, MD, and Hamid Ikram, MD trial natriuretic factor (ANF) administered to norA mal humans induces natriuresis and diuresis, suppressesrenin-angiotensin-aldosteronesystemactivity and may lower blood pressure.’ In patients with congestive heart failure (CHF), ANF given as an intravenous bolus has been reported to have natriuretic and vasodilator effects.*y3Constant infusions of ANF also exert favorable effects on hemodynamic parameters in CHF with decreasesin both cardiac preload and afterload and improvement of cadiac output.4 We compared the clinical efficacy of ANF and furosemideadministered as a single daily intravenous bolus to patients with chronic stable CHF. We studied 4 men aged 62 to 75 years with chronic stable CHF. Two patients had coronary artery disease and 2 had idiopathic dilated cardiomyopathy. In all, left ventricular failure with radiologically documented pulmonary edema had occurred at some point between 1 and 6 years before the study. All 4 patients were stable with furosemide treatment alone (40 to 80 mglday) except for 1 patient with atria1 fibrillation who was also receiving digoxin, 0.25 mg daily. At the time of entry to the study, 2 patients were in New York Heart Association functional class II and 2 were in class III. Left ventricular ejection fraction measured by angiogram or echocardiography ranged from 28 to 38%. All 4 patients had stable symptoms and clinical signs for at least 1 month with oral furosemide treatment before commencement of the first ANF study phase. At entry patients abstained from medications for I day during which a physical examination was conducted, blood was drawn for routine hematologylbiochemistry tests and a chest x-ray was taken. A supine bicycle
Fromthe Departments of Cardiology and Endocrinology, the Princess Margaret Hospital, Christchurch 2, New Zealand. Manuscript receivedApril 26, 1989; revised manuscript received and acceptedJuly 5, 1989.
948
THE AMERICAN JOURNAL OF CARDIOLOGY VOLUME 64
exercise test (modified Naughton protocol) was performed. Patients then attended the outpatient clinic daily between 8 and IO A.M. and received single bolus intravenous injections of furosemide and ANF given in random order, single-blind, for 14 days on each agent. Body weight, blood pressure and symptomatic status were recorded daily before each dose. Twenty-four hour urine collections for measurement of sodium and plasma were obtained on days I, 2,3,5,10 and 13 of each study phase. A 24-hour Holter monitor was recorded the day before doses began and on day 13 of each phase. Exercise tests were repeated on day 14 of each study phase. The starting dose chosen for intravenous furosemide was 20 mg with an increase to 40 mg if weight increased. Isoleucine ANF (101-126) was begun at 200 pg daily with daily dosage increments of up to 200 pg if body weight increased or symptoms worsened. Patient 3 was the only patient to complete the study. He received furosemide 40 mg and ANF 240 pg daily, respectively. Symptomatic status, weight (Figure I), blood pressure and plasma biochemistry remained unchanged throughout both study phases. This patient, however, reported that while receiving ANF he urinated very little during the day and developed nocturia. Patients 1, 2 and 4 were withdrawn from the study after 8,9 and 2 days of treatment with ANF because of progressive CHF despite receiving 1,000, 1,000 and 240 Fg daily of ANF at withdrawal, respectively. Body weight clearly increased in patients 1 and 2 (Figure 1). After withdrawal from the study and administration of 40 mg intravenous furosemide and reintroduction of maintenance furosemide, the patients rapidly returned to their pretrial status. Twenty-four hour urinary sodium excretions averaged for data from days 1, 2, 3, 5, 10 and 13 of the furosemide treatment phase were 105 and IO7 mmol/day for patients I and 3, respectively (the 2 subjects completing this study phase). Urine sodium excretion averaged
for days 1,2, 3 and 5 of ANF treatment was 52 mmol/ dayforpatient 1 (withdrawn on day 8) and 83 mmollday for patient 3 (completed phase). Average 24-hour sodium excretions for patients 2 and 4 who began, but failed to complete, the ANF study phase alone, were 46 (days 1, 2, 3 and 5) and 35 mmol/day (day I), respectively. Pretrial exercise durations were 6,12, I5 and 9 minutes for patients 1 to 4, respectively. Only Zpatients (1 and 3) had further tests for comparison. At the completion of the furosemide phase exercise durations were 6 and 18 minutes for patients 1 and 3, respectively. The only subject (patient 3) to undergo the third test (completion of ANF phase) exercised for 15 minutes at that time. Holter monitoring revealed no notable change in the occurrence of ventricular ectopic activity or other abnormalities of cardiac rhythm with the serial recordings conductedin 2 patients (patients 1 and 3). All 4 subjects had well-maintained systemic arterial pressure (between 125/70 and 174/85 mm Hg) throughout the study. There were no notable changes in arterial pressure in any individual subject either within or between study phases. No patient experienced acute adverse reactions to intravenous bolus injections of even the peak doses (1,000 ug intravenous over 2 minutes) of ANF used. In particular, hypotension did not occur.
A single daily doseof ANF (intravenous bolusadministration up to 1,000pg) wasclearly ineffective in controlling CHF in ambulatory patients previously stable with furosemide treatment. The bioactivity of the ANF solution usedwas confirmed by the clear beneficial hemodynamic effectsseenin a placebo-controlledstudy in which ANF from the same batch was administered as a constant infusion (5 ug/min) to a group of patients with CHF.4 The 1 patient completing both trial phaseshad the best pretrial exercisetolerance and ventricular ejection fraction. Nevertheless,he exhibited reduced 24-hour sodium excretion and reported a decreasein daytime urine volume and the onset of nocturia while receiving ANF. Thesefeatures suggestthe presenceof sufficient cardiac reserveto preservea relatively compensatedstate when furosemide was withdrawn-not effective treatment by ANF. The underlying mechanismsfor such relative resistance to bolus ANF therapy are uncertain. The stimulus of brief pharmacologic levels of plasma ANF (half-life approximately 3 minutes), even though the biologic effects are more prolonged,*,3v4 may simply be too shortlived to exert sustainedeffects.Higher dosesmay be more effective eventhough the dosesusedin the presentstudy exceededthose usedin any other bolus study reported to
+
PATIENT 1 ( F / ANF )
t 3
64.0 -
\
f % 62.0 -
/do\/--\
PA
I**
/
'a
f
60.0 PATIENT 2 ( ANF / F )
WEIGHT 14.0 -
/*y
( kg 1 0' .I
72.0 -
\
l
O-.’
PATIENT 3 ( F / ANF 1 81.0 -0-e
79.0-k
'I,.+ r/' \ .I.......,................., 5
,*,. 10
'~~oJ-'~L~,.-. 15
20
25
DAYS -boLa~ofeither-(F) ofbottyweightin3patienbrecehhgdaify factor (ANF) (F/ANF) oc vice versa (ANF/F) for 14 days on etad~agent. The amowhearb indicate Afowthrubjsctwaswilhdrawnafter #naofwlfh&awdfromANFfmafmedand-ofintravenous~. lIldY4ShOWSdANF fmabmnf~ofacu&left~f~.
FmUNE
1. Day
B
fo&wedbyMrvbLrstk
THE AMERICAN JOURNAL OF CARDIOLOGY OCTOBER 15,1989
949
BMEFREPoRTs date.‘e3The present dosagewas similar to the total dose adjunctive therapy in the management of patients with infused over 4 hours in similar patients, which resulted in CHF. clear hemodynamic benefit.4 The inefficacy of daily single dosebolus intravenous 1. Richards AM, Ikram H, Yandle TG, Nicholls MG, Webster MWI, Espiner Renal,haemodynamic, and hormonal effects of humanalpha atrial natriuretANF exhibited in this study doesnot necessarilyindicate icEA.peptide in healthy volunteers. Lancer 1985;1;545-549. the total absenceof a therapeutic role for ANF. Con- 3. Riegger AJG, Kramer KP, Kochsiek K. Dar natriuretische vorhoffaktor bei stant-doseinfusions of ANF have been shown to exert schwerer kongestiver herzinsuffiienz. Dtsch Med Wochenschr 1985;110:16071610. beneficial effects.4It remains possible that maneuvers 3. Tang J, Xie CW, Jiang BQ, Xu YY, Zhang JY, Meng ZH, Wu HJ, Liu LS, directed at causing relatively subtle but sustainedincre- Chann- D. Chana JK. Theraneutic actions of w-humanatria1 natriuretic polypepments in plasma ANF, either by providing orally bio- tide in 16 &i&l cases.Ii& Sci 1987;40:2077-2084. 4. Cmzier IG, Ikram H, Gomez HJ, Nicholls MG, Eapiner EA. Warner NJ. active analogsor by use of an inhibitor of degradation of Haemodynamic effects of atria1 paptide infusion in heart failure. Lancer endogenouspeptide, may yet play a role as either sole or 1986;2:1242-I 245.
Echocardiographic Detection and Clinical Significance of Left Atrial Vegetations in Active Infective Endocarditis Jerome H. Kim, MD, Alan Wiseman, MD, Joseph Kisslo, MD, and David T. Durack, MB, DPhil nvolvement of the mural endocardium during infective endocarditis (IE) was commonly reported in early Iseries of patients,lo*but little new information has been added since antibiotic therapy dramatically reduced the mortality of this condition. Mural vegetations are thought to developin 2 ways. The more commoninvolves growth of a vegetation at the site of a “jet lesion,” that is, the impact site of a regurgitant stream. Much lesscommon is isolated, primary mural endocarditis-through 1978there had beenonly 22 reported cases3Two-dimenFrom the Department of Medicine, Division of Infectious Diseases,Box 3123, Duke University Medical Center, Durham, North Carolina 27710. Manuscript received January 26, 1989;revised manuscript re ceived and acceptedJuly 3,1989.
FlGUREl.mlv~~inleft~storndbng-axkvlow,hsEastob,ofapatlmtwlthIE, (arrow)osltho~wdol *amwmMoa thOlCdtSWhl(LA),JUStdOVOthSlOVOlOfthSlIllld u*+a.ThOmibdV~~-bOSSSSlClOaSiylll
tMsvlow.BYrotamgths-
sughuy off-axis,
the2bbesofthev~&athcanbeseen.Ao=aodcrooQ Lv=loftvsnbido.
990
THE AMERICAN JOURNAL OF CARDIOLOGY VOLUME 64
sional echocardiographycan detect vegetationsof IE in 43 to 100%of patients4 Someinvestigatorshave suggested that the detection of vegetationsby echocardiography may identify a subgroup of patients at higher risk for embolic complications.4-6Others have included it as a minor criterion for surgical intervention in active IE.7 Mural vegetations have not been well characterized echocardiographically, nor has their clinical significance been studied in detail. We report 6 patients with IE and left atria1 (LA) massesdemonstrated by 2diiensional echocardiography.Doppler color flow imaging revealeda regurgitant stream striking endocardium at the base of the vegetationin all patients. Transesophagealechocardiography proved an excellent technique to study the location and size of vegetationsattached to the posterior LA wall, which is difficult to visualize by standard 2-dimensional echocardiography. We reviewed the Duke University Medical Center echocardiography log books for the years 1982 through 1988 for patients with mitral regurgitation and vegetations found by echocardiogram. Six patients were identified. Two-dimensional echocardiography and Doppler color jlow imaging were performed using a HewlettPackard 77020 AU ultrasound imager equipped with a 2.5MHz phased-array transducer or an Interspec Vingmed mechanical scanner. In each study, standard 2dimensional views were obtained. The LA vegetations were visible on multiple views in all 6 patients. The parasternal long-axis view was usually the best. Transesophageal echocardiography was performed with a 5.0MHz Hewlett-Packard transesophageal probe. All echocardiograms were reviewed by A W and JK. All patients were in sinus rhythm. A history of intravenous drug abuse was obtained from 4 of the 6 patients and rheumatic heart disease from 2. Mitral valve prolapse was present in I patient. The LA vegetation was posterior in 5 and anterior in 1; in each instance the regurgitant jet was directed at the lesion. The degree of mitral regurgitation, as assessedechocardiographically, varied from mild to severe based on the size of the regur-
2. Perry GJ, Nanda NC. Recent advancesin color flow Doppler assessmentof valvular regurgitation. Echocardiography 1987;4:503-513. 4. Cornyn JW, Massie BM, Unverferth DV, L&r CV. Hemodynamic changes after meals and placebo treatment in chronic congestive heart failure. Am J Cardiol 1986;57:238-241.
5. HiUis LD, Fiih BG, Winniford MD. Analysis of factors affecting the variability of Fick versusindicator dilution measurementsof cardiac output. Am J Cardiol 1985:56:764-768.
9. Rubin SA, SiemienczukD, Nathan MD, PrauseJ, Swan HJC. Accuracy of
cardiac output, oxygenuptake,and arteriovenousoxygendifference at rest,during exercise, and after vasodilator therapy in patients with severe, chronic heart failure. Am J Cardiol 1982;50:973-978. 7. Kashtan HI, Maitland A, Salerno TA, Lichtenstein SV, Byrick RJ. Effects of tricuspid regurgitation on thermodilution cardiac output: studies in an animal model. Can J Anaesth 1987;34:246-251. 8. Beyer J, Lamberti JJ, Replogle RL. Validity of therm&&on cardiac output determination:experimental studieswith and without pulmonary insufficiency. J Surg Res 1976;21:313-317.
9. Van Grondelle A, Ditchey RV, Groves BM, Wagner WW, ReevesJT. Thermodilution method overestimateslow cardiac output in humans.Am J Physiol 1983;245:H690-H692.
10. Venkatamaran K, De Guzman M, Hafeezkhan A, Haywood LJ. Cardiac output measurement:a comparisonof direct Fick, dye dilution and thermcdilution methodsin stable and acutely ill patients. J NatI Med Assoc 1976,68:281-284.
Inefficacy of Daily Single Bobs Dose Atrial Natriuretic in Chronic Congestive Heart Failure
Factor
Ian G. Crozier, MD, A. Mark Richards, MD, M. Gary Nicholls, MD, Eric A. Espiner, MD, and Hamid Ikram, MD trial natriuretic factor (ANF) administered to norA mal humans induces natriuresis and diuresis, suppressesrenin-angiotensin-aldosteronesystemactivity and may lower blood pressure.’ In patients with congestive heart failure (CHF), ANF given as an intravenous bolus has been reported to have natriuretic and vasodilator effects.*y3Constant infusions of ANF also exert favorable effects on hemodynamic parameters in CHF with decreasesin both cardiac preload and afterload and improvement of cadiac output.4 We compared the clinical efficacy of ANF and furosemideadministered as a single daily intravenous bolus to patients with chronic stable CHF. We studied 4 men aged 62 to 75 years with chronic stable CHF. Two patients had coronary artery disease and 2 had idiopathic dilated cardiomyopathy. In all, left ventricular failure with radiologically documented pulmonary edema had occurred at some point between 1 and 6 years before the study. All 4 patients were stable with furosemide treatment alone (40 to 80 mglday) except for 1 patient with atria1 fibrillation who was also receiving digoxin, 0.25 mg daily. At the time of entry to the study, 2 patients were in New York Heart Association functional class II and 2 were in class III. Left ventricular ejection fraction measured by angiogram or echocardiography ranged from 28 to 38%. All 4 patients had stable symptoms and clinical signs for at least 1 month with oral furosemide treatment before commencement of the first ANF study phase. At entry patients abstained from medications for I day during which a physical examination was conducted, blood was drawn for routine hematologylbiochemistry tests and a chest x-ray was taken. A supine bicycle
Fromthe Departments of Cardiology and Endocrinology, the Princess Margaret Hospital, Christchurch 2, New Zealand. Manuscript receivedApril 26, 1989; revised manuscript received and acceptedJuly 5, 1989.
948
THE AMERICAN JOURNAL OF CARDIOLOGY VOLUME 64
exercise test (modified Naughton protocol) was performed. Patients then attended the outpatient clinic daily between 8 and IO A.M. and received single bolus intravenous injections of furosemide and ANF given in random order, single-blind, for 14 days on each agent. Body weight, blood pressure and symptomatic status were recorded daily before each dose. Twenty-four hour urine collections for measurement of sodium and plasma were obtained on days I, 2,3,5,10 and 13 of each study phase. A 24-hour Holter monitor was recorded the day before doses began and on day 13 of each phase. Exercise tests were repeated on day 14 of each study phase. The starting dose chosen for intravenous furosemide was 20 mg with an increase to 40 mg if weight increased. Isoleucine ANF (101-126) was begun at 200 pg daily with daily dosage increments of up to 200 pg if body weight increased or symptoms worsened. Patient 3 was the only patient to complete the study. He received furosemide 40 mg and ANF 240 pg daily, respectively. Symptomatic status, weight (Figure I), blood pressure and plasma biochemistry remained unchanged throughout both study phases. This patient, however, reported that while receiving ANF he urinated very little during the day and developed nocturia. Patients 1, 2 and 4 were withdrawn from the study after 8,9 and 2 days of treatment with ANF because of progressive CHF despite receiving 1,000, 1,000 and 240 Fg daily of ANF at withdrawal, respectively. Body weight clearly increased in patients 1 and 2 (Figure 1). After withdrawal from the study and administration of 40 mg intravenous furosemide and reintroduction of maintenance furosemide, the patients rapidly returned to their pretrial status. Twenty-four hour urinary sodium excretions averaged for data from days 1, 2, 3, 5, 10 and 13 of the furosemide treatment phase were 105 and IO7 mmol/day for patients I and 3, respectively (the 2 subjects completing this study phase). Urine sodium excretion averaged
for days 1,2, 3 and 5 of ANF treatment was 52 mmol/ dayforpatient 1 (withdrawn on day 8) and 83 mmollday for patient 3 (completed phase). Average 24-hour sodium excretions for patients 2 and 4 who began, but failed to complete, the ANF study phase alone, were 46 (days 1, 2, 3 and 5) and 35 mmol/day (day I), respectively. Pretrial exercise durations were 6,12, I5 and 9 minutes for patients 1 to 4, respectively. Only Zpatients (1 and 3) had further tests for comparison. At the completion of the furosemide phase exercise durations were 6 and 18 minutes for patients 1 and 3, respectively. The only subject (patient 3) to undergo the third test (completion of ANF phase) exercised for 15 minutes at that time. Holter monitoring revealed no notable change in the occurrence of ventricular ectopic activity or other abnormalities of cardiac rhythm with the serial recordings conductedin 2 patients (patients 1 and 3). All 4 subjects had well-maintained systemic arterial pressure (between 125/70 and 174/85 mm Hg) throughout the study. There were no notable changes in arterial pressure in any individual subject either within or between study phases. No patient experienced acute adverse reactions to intravenous bolus injections of even the peak doses (1,000 ug intravenous over 2 minutes) of ANF used. In particular, hypotension did not occur.
A single daily doseof ANF (intravenous bolusadministration up to 1,000pg) wasclearly ineffective in controlling CHF in ambulatory patients previously stable with furosemide treatment. The bioactivity of the ANF solution usedwas confirmed by the clear beneficial hemodynamic effectsseenin a placebo-controlledstudy in which ANF from the same batch was administered as a constant infusion (5 ug/min) to a group of patients with CHF.4 The 1 patient completing both trial phaseshad the best pretrial exercisetolerance and ventricular ejection fraction. Nevertheless,he exhibited reduced 24-hour sodium excretion and reported a decreasein daytime urine volume and the onset of nocturia while receiving ANF. Thesefeatures suggestthe presenceof sufficient cardiac reserveto preservea relatively compensatedstate when furosemide was withdrawn-not effective treatment by ANF. The underlying mechanismsfor such relative resistance to bolus ANF therapy are uncertain. The stimulus of brief pharmacologic levels of plasma ANF (half-life approximately 3 minutes), even though the biologic effects are more prolonged,*,3v4 may simply be too shortlived to exert sustainedeffects.Higher dosesmay be more effective eventhough the dosesusedin the presentstudy exceededthose usedin any other bolus study reported to
+
PATIENT 1 ( F / ANF )
t 3
64.0 -
\
f % 62.0 -
/do\/--\
PA
I**
/
'a
f
60.0 PATIENT 2 ( ANF / F )
WEIGHT 14.0 -
/*y
( kg 1 0' .I
72.0 -
\
l
O-.’
PATIENT 3 ( F / ANF 1 81.0 -0-e
79.0-k
'I,.+ r/' \ .I.......,................., 5
,*,. 10
'~~oJ-'~L~,.-. 15
20
25
DAYS -boLa~ofeither-(F) ofbottyweightin3patienbrecehhgdaify factor (ANF) (F/ANF) oc vice versa (ANF/F) for 14 days on etad~agent. The amowhearb indicate Afowthrubjsctwaswilhdrawnafter #naofwlfh&awdfromANFfmafmedand-ofintravenous~. lIldY4ShOWSdANF fmabmnf~ofacu&left~f~.
FmUNE
1. Day
B
fo&wedbyMrvbLrstk
THE AMERICAN JOURNAL OF CARDIOLOGY OCTOBER 15,1989
949
BMEFREPoRTs date.‘e3The present dosagewas similar to the total dose adjunctive therapy in the management of patients with infused over 4 hours in similar patients, which resulted in CHF. clear hemodynamic benefit.4 The inefficacy of daily single dosebolus intravenous 1. Richards AM, Ikram H, Yandle TG, Nicholls MG, Webster MWI, Espiner Renal,haemodynamic, and hormonal effects of humanalpha atrial natriuretANF exhibited in this study doesnot necessarilyindicate icEA.peptide in healthy volunteers. Lancer 1985;1;545-549. the total absenceof a therapeutic role for ANF. Con- 3. Riegger AJG, Kramer KP, Kochsiek K. Dar natriuretische vorhoffaktor bei stant-doseinfusions of ANF have been shown to exert schwerer kongestiver herzinsuffiienz. Dtsch Med Wochenschr 1985;110:16071610. beneficial effects.4It remains possible that maneuvers 3. Tang J, Xie CW, Jiang BQ, Xu YY, Zhang JY, Meng ZH, Wu HJ, Liu LS, directed at causing relatively subtle but sustainedincre- Chann- D. Chana JK. Theraneutic actions of w-humanatria1 natriuretic polypepments in plasma ANF, either by providing orally bio- tide in 16 &i&l cases.Ii& Sci 1987;40:2077-2084. 4. Cmzier IG, Ikram H, Gomez HJ, Nicholls MG, Eapiner EA. Warner NJ. active analogsor by use of an inhibitor of degradation of Haemodynamic effects of atria1 paptide infusion in heart failure. Lancer endogenouspeptide, may yet play a role as either sole or 1986;2:1242-I 245.
Echocardiographic Detection and Clinical Significance of Left Atrial Vegetations in Active Infective Endocarditis Jerome H. Kim, MD, Alan Wiseman, MD, Joseph Kisslo, MD, and David T. Durack, MB, DPhil nvolvement of the mural endocardium during infective endocarditis (IE) was commonly reported in early Iseries of patients,lo*but little new information has been added since antibiotic therapy dramatically reduced the mortality of this condition. Mural vegetations are thought to developin 2 ways. The more commoninvolves growth of a vegetation at the site of a “jet lesion,” that is, the impact site of a regurgitant stream. Much lesscommon is isolated, primary mural endocarditis-through 1978there had beenonly 22 reported cases3Two-dimenFrom the Department of Medicine, Division of Infectious Diseases,Box 3123, Duke University Medical Center, Durham, North Carolina 27710. Manuscript received January 26, 1989;revised manuscript re ceived and acceptedJuly 3,1989.
FlGUREl.mlv~~inleft~storndbng-axkvlow,hsEastob,ofapatlmtwlthIE, (arrow)osltho~wdol *amwmMoa thOlCdtSWhl(LA),JUStdOVOthSlOVOlOfthSlIllld u*+a.ThOmibdV~~-bOSSSSlClOaSiylll
tMsvlow.BYrotamgths-
sughuy off-axis,
the2bbesofthev~&athcanbeseen.Ao=aodcrooQ Lv=loftvsnbido.
990
THE AMERICAN JOURNAL OF CARDIOLOGY VOLUME 64
sional echocardiographycan detect vegetationsof IE in 43 to 100%of patients4 Someinvestigatorshave suggested that the detection of vegetationsby echocardiography may identify a subgroup of patients at higher risk for embolic complications.4-6Others have included it as a minor criterion for surgical intervention in active IE.7 Mural vegetations have not been well characterized echocardiographically, nor has their clinical significance been studied in detail. We report 6 patients with IE and left atria1 (LA) massesdemonstrated by 2diiensional echocardiography.Doppler color flow imaging revealeda regurgitant stream striking endocardium at the base of the vegetationin all patients. Transesophagealechocardiography proved an excellent technique to study the location and size of vegetationsattached to the posterior LA wall, which is difficult to visualize by standard 2-dimensional echocardiography. We reviewed the Duke University Medical Center echocardiography log books for the years 1982 through 1988 for patients with mitral regurgitation and vegetations found by echocardiogram. Six patients were identified. Two-dimensional echocardiography and Doppler color jlow imaging were performed using a HewlettPackard 77020 AU ultrasound imager equipped with a 2.5MHz phased-array transducer or an Interspec Vingmed mechanical scanner. In each study, standard 2dimensional views were obtained. The LA vegetations were visible on multiple views in all 6 patients. The parasternal long-axis view was usually the best. Transesophageal echocardiography was performed with a 5.0MHz Hewlett-Packard transesophageal probe. All echocardiograms were reviewed by A W and JK. All patients were in sinus rhythm. A history of intravenous drug abuse was obtained from 4 of the 6 patients and rheumatic heart disease from 2. Mitral valve prolapse was present in I patient. The LA vegetation was posterior in 5 and anterior in 1; in each instance the regurgitant jet was directed at the lesion. The degree of mitral regurgitation, as assessedechocardiographically, varied from mild to severe based on the size of the regur-