- Email: [email protected]
The spectrum of pulmonary abnormalities on computed chest tomographic imaging in patients with advanced heart failure
Matsuo H. Endothelial cells actively synthesize and secrete adrenomedullin. Biochem Biophys Res Commun 1994;201:1160 –1166. 3. Ichiki Y, Kitamura K, Kangawa K, Kawamoto M, Matsuo H, Eto T. Distribution and characterization of immunoreactive adrenomedullin in human tissue and plasma. FEBS Lett 1994;338:6 –10. 4. Nishikimi T, Horio T, Sasaki T, Yoshihara F, Takishita S, Miyata A, Matsuoka H, Kangawa K. Cardiac production and secretion of adrenomedullin are increased in heart failure. Hypertension 1997;30:1369 –1375. 5. Nishikimi T, Saito Y, Kitamura K, Ishimitsu T, Eto T, Kangawa K, Matsuo H, Omae T, Matsuoka H. Increased plasma level of adrenomedullin in patients with heart failure. J Am Coll Cardiol 1995;26:1424 –1431. 6. Nagaya N, Nishikimi T, Horio T, Yoshihara F, Kanazawa A, Matsuo H, Kangawa K. Cardiovascular and renal effects of adrenomedullin in rats with heart failure. Am J Physiol 1999;276:R213–218. 7. Ishizaka Y, Ishizaka Y, Tanaka M, Kitamura K, Kangawa K, Minamino N, Matsuo H, Eto T. Adrenomedullin stimulates cyclic AMP formation in rat vascular smooth muscle cells. Biochem Biophys Res Commun 1994;200:642– 646. 8. Lainchbury JG, Cooper GJS, Coy DH, Jiang N-Y, Lewis LK, Yandle TG, Richards AM, Nicholls MG. Adrenomedullin: a hypotensive hormone in man. Clin Sci 1997;92:467– 472. 9. Nakagawa H, Okumura K, Hashimoto H, Ito T, Ogawa K, Sakata T. Effects of atrial natriuretic polypeptide and organic nitrates on levels of relaxation and cyclic nucleotide of canine coronary artery with and without endothelial injury. Heart Vessels 1988;4:19 –25. 10. Semigran MJ, Aroney CN, Hermann NC, Dec GW, Boucher CA, Fifer MA. Effects of atrial natriuretic peptide on myocardial contractile and diastolic function in patients with heart failure. J Am Coll Cardiol 1992;20:98 –106. 11. Parks DG, May CN. Direct cardiac and vascular actions of adrenomedullin in conscious sheep. Br J Pharmacol 1997;120:1179 –1185.
12. Szokodi I, Kinnunen P, Weckstrom M, Toth M, Ruskoaho H. Evidence for
cAMP-dependent mechanisms mediating the effects of adrenomedullin, a new inotropic peptide. Circulation 1998;97:1062–1070. 13. Nagaya N, Nishikimi T, Okano Y, Uematsu M, Satoh T, Kyotani S, Kuribayashi S, Hamada S, Kakishita M, Nakanishi N, Takamiya M, Kunieda T, Matsuo H, Kangawa K. Plasma brain natriuretic peptide levels increase in proportion to the extent of right ventricular dysfunction in pulmonary hypertension. J Am Coll Cardiol 1998;31:202–208. 14. Nakamura M, Yoshida H, Funakoshi T, Arakawa N, Hiramori K. Renal, hemodyanmic and hormonal interactions between atrial natriuretic factor and arginine vasopressin in patients with congestive heart failure. Clin Sci 1992;82: 363–368. 15. Hirata Y, Hayakawa H, Suzuki Y, Suzuki E, Ikenouchi H, Kohmoto O, Kimura K, Kitamura K, Eto T, Kangawa K, Matsuo H, Omae M. Mechanisms of adrenomedullin-induced vasodilation in the rat kidney. Hypertension 1995;25: 790 –795. 16. Fukuhara M, Tsuchihashi T, Abe I, Fujishima M. Cardiovascular and neurohormonal effects of intravenous adrenomedullin in conscious rabbits. Am J Physiol 1995;269:R1289 –R1293. 17. Lainchbury JG, Nicholls MG, Espiner EA, Yandle TG, Lewis LK, Richards AM. Bioactivity and interactions of adrenomedullin and brain natriuretic peptide in patients with heart failure. Hypertension 1999;34:70 –75. 18. Edwards RM, Trixna W, Stack E, Aiyar N. Effect of adrenomedullin on cAMP levels along the rat nephron: comparison with CGRP. Am J Physiol 1996;271:F895–F899. 19. Brenner BM, Ballermann BJ, Gunning ME, Zeidel ML. Diverse biological actions of natriuretic peptide. Physiol Rev 1990;70:665– 699. 20. Yamaguchi T, Baba K, Doi Y, Yano K. Effect of adrenomedullin on aldosterone secretion by dispersed rat adrenal zona glomerulosa cells. Life Sci 1995;56:379 –387.
The Spectrum of Pulmonary Abnormalities on Computed Chest Tomographic Imaging in Patients With Advanced Heart Failure Sami Lewin,
BS,
Lee Goldberg,
MD, MPH,
valuation of potential candidates for heart transplantation involves extensive diagnostic testing E that occasionally includes computed tomographic (CT) imaging of the chest. Radiologic finding on chest computed tomography of acute pulmonary edema have been described and include smooth septal thickening, “ground glass” opacities, alveolar consolidation, vascular redistribution, pleural effusions, and cardiomegaly.1,2 Mediastinal lymphadenopathy has also recently been described.3 Prior studies have focused on CT studies obtained to assess noncardiac conditions and have not described findings specifically associated with a chronic heart failure population. •••
The study cohort was selected from ⬎400 consecutive patients referred to the Heart Failure and Cardiac Transplantation Service of the Massachusetts General Hospital between January 1, 1992, and June 1, 1998, for inpatient cardiac transplantation evaluation. Chest CT imaging studies were ordered at the discretion of From the Heart Failure and Transplantation Service, Division of Cardiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; University of Buffalo School of Medicine, Buffalo, New York; and Cardiology Division, University of Pennsylvania, Philadelphia, Pennsylvania. Dr. Dec’s address is: Heart Failure and Transplantation Center, Massachusetts General Hospital, Bigelow 645 Fruit Street, Boston, Massachusetts 02114. E-mail: [email protected]. Manuscript received November 10, 1999; revised manuscript received and accepted January 12, 2000.
98
©2000 by Excerpta Medica, Inc. All rights reserved. The American Journal of Cardiology Vol. 86 July 1, 2000
and G. William Dec,
MD
the attending transplant cardiologist and were usually obtained in patients who have had abnormal chest x-rays, markedly abnormal pulmonary function tests (forced expiratory volume in 1 second, vital capacity, or corrected diffusion capacity ⬍50% of predicted for age), a known pulmonary illness such as sarcoidosis or obstructive lung disease, unexplained pulmonary hypertension, or risk factors for lung malignancy. From a medical records review, we identified 71 patients who had a chest CT scan recorded as a part of their pretransplant evaluation. CT scans were reviewed with a board-certified chest radiologist to determine the nature and frequency of abnormal findings associated with chronic heart failure. The presence, size, and location of mediastinal lymph nodes were evaluated. Lymph nodes ⬎1 cm in diameter were considered physiologically abnormal. Demographic data including age, sex, diagnosis, duration of symptoms, prior chest surgery, New York Heart Association class, and history of smoking were included in the analysis. Right-sided cardiac catheterization and hemodynamic assessment were performed via the right internal jugular vein in all but 1 pediatric patient. CT scans were performed using standard institutional protocol without administration of intravenous contrast on a 9800 scanner (General Electric Medical Systems, Milwaukee, Wisconsin)3 All descriptive data are given as mean ⫾ 1 SD. 0002-9149/00/$–see front matter PII S0002-9149(00)00837-7
TABLE I Patient Characteristics and Hemodynamics
TABLE II Findings on CT Imaging of the Chest in Advanced Heart Failure
Parameter Age (ys) Gender Men Women Heart failure etiology Ischemic Dilated Valvular Other Smoking history Duration of symptoms (wks) Prior thoracic surgery Left ventricular ejection fraction New York Heart Association class II III IV Resting hemodynamics Right atrial pressure (mmHg) Pulmonary artery septolic pressure (mmHg) Mean pulmonary artery pressure (mmHg) Pulmonary artery diastolic pressure (mmHg) Mean pulmonary capillary wedge pressure (mm Hg) Cardiac index (L/min/m2)
52 ⫾ 10 77% 23% 48% 38% 4% 10% 63% 172 ⫾ 230 24% 21% ⫾ 8% 10% 53% 37% 10 51 35 25 23
⫾ ⫾ ⫾ ⫾ ⫾
7 20 12 10 10
2.1 ⫾ 0.6
Values are expressed mean ⫾ SEM.
Unpaired Student’s t test and Fisher’s exact test were used to compare differences in variables between groups. Multiple variable analysis was performed using logistic regression modeling (SAS Institute, Cary, North Carolina). The outcome of interest was defined as lymph nodes ⬎1 cm. The model simultaneously controlled for mean pulmonary capillary wedge pressure, age, sex, and smoking history. The mean ⫾ SD age of the study population was 52 ⫾ 10 years; there were 17 women and 54 men (Table I). Heart failure etiology was divided between ischemic heart disease and idiopathic dilated cardiomyopathy (Table I). Although the average duration of heart failure exceeded 3 years, symptoms ranged from ⬍1 week to ⬎20 years. Most patients had New York Heart Association functional class III or IV symptoms consistent with their referral for transplant evaluation. Resting hemodynamics confirmed chronic heart failure with mean pulmonary capillary wedge pressure ⬎20 mm Hg and cardiac index ⬍2.2 L/min/m2 despite optimal diuretic and vasodilator therapy (Table I). Chest CT scans were obtained in 6 patients because of a prior history of “cured” malignancy that included non-Hodgkin’s lymphoma (n ⫽ 2), childhood sarcoma (n ⫽ 1), colonic carcinoma in situ (n ⫽ 1), breast carcinoma (n ⫽ 1), and prostate carcinoma (n ⫽ 1). Four additional patients underwent evaluation for known granulomatous disease: systemic sarcoidosis (n ⫽ 3), treated tuberculosis (n ⫽ 1). Three other patients had undergone previous lobectomy and underwent CT imaging to better define their pulmonary anatomy. Most patients (n ⫽ 58) had parenchymal abnormalities on admission chest x-ray film (n ⫽ 22),
CT Finding* Pulmonary edema “Ground glass” appearance Alveolar edema Interstitial edema Reticulonodular pattern Pleural effusion Bilateral Right sided Left sided Pulmonary nodules Discrete Multiple Calcification Granulomatous Lymphadenopathy Atelectasis Emphysema Interstitial fibrosis Radiation induced Amiodarone Diffuse Focal consolidation /pneumonia Pulmonary venous redistribution Pulmonary arterial enlargement Other Bronchiectasis Cavitary lesion Foreign body (bullet) Lobectomy Normal
Patients 37 18 12 4 3 31 16 7 8 28 4 12 2 10 25 20 19 7 3 1 3 6 7 9 7 2 1 1 3 0
(52%) (25%) (17%) (6%) (4%) (44%) (28)%) (10%) (11%) (39%) (6%) (17%) (3%) (14%) (35%) (28%) (27%) (10%) (4%) (1%) (4%) (8%) (10%) (13%) (10%) (3%) (1%) (1%) (4%) (0%)
*Findings add up to ⬎100% because many patients had multiple findings.
TABLE III Location of Mediastinal Adenopathy in Patients With Advanced Heart Failure
Location of Nodes Precarinal Pretracheal Paratracheal Prevascular Subcarinal
No. of Patients (n ⫽ 25) and Overall %* 12 6 4 9 7
(48%) (24%) (16%) (36%) (28%)
*The percentage of patients who had at least 1 lymph node ⬎1 cm on CT imaging in that region.
prominent pulmonary arteries (n ⫽ 8), or impairment of pulmonary function tests exceeding that typically observed in patients with chronic heart failure (n ⫽ 28). One or more CT abnormalities were noted in all 71 patients (Table II). Pleural effusions were quite common (44%) and were most often observed bilaterally. A “ground glass” appearance was seen in 25% of patients and prominent alveolar edema was noted in 17% of cases. Pulmonary nodules were common (39%) and displayed a variety of patterns ranging from discrete nodules and multiple scattered granulomata to a diffuse reticulonodular pattern (Table II). Nodule size was typically 3 to 5 mm but could reach ⱖ10 mm. Calcium was quite uncommon. Mediastinal lymph nodes were absent in 27 patients (38%). NineBRIEF REPORTS
99
teen patients (27%) had nonpathologic lymph nodes (⬍1 cm along the short axis); the remaining 25 patients (35%) had ⱖ1 node ⬎1 cm in size. Lymphadenopathy did not exceed 2 cm in any patient. The locations of the enlarged lymph nodes are summarized in Table III. Nodal calcification was quite uncommon and seen in only 2.8% of cases. Repeat CT imaging was performed in 9 patients with visible lymphadenopathy. No change was noted in the extent or location of these nodes on repeat CT imaging. Lymph node biopsy was performed in 3 of the 5 patients with multiple mediastinal nodes (⬎1 cm). A prominent reactive histiocytic infiltrate was present in each case. In a multiple logistic regression that examined the effect of age, gender, resting pulmonary capillary wedge pressure, smoking history, and a history of granulomatous disease, no significant predictors for lymphadenopathy were identified. •••
CT findings did not preclude listing in any patient. However, 1 patient developed hemodynamic instability and died of multiorgan failure 48 hours after biopsy. A second patient developed lung adenocarcinoma 18 months after transplantation. Seven months before transplantation, a single 1-cm subcarinal lymph node was noted. Repeat CT imaging disclosed the interim development of 1- to 2.5-cm lymph nodes in the left internal mammary chain and a new mediatinal mass. The subcarinal node was no longer evident. The remaining 19 transplant recipients remain free of malignancy or active infection. CT findings in populations with chronic heart failure have not been previously described. It is well known that chronic heart failure leads to enhanced lymphatic drainage of the pulmonary parenchyma as a compensatory mechanism for chronic elevation in left-sided filling pressures. Hence, the typical CT findings seen during acute heart failure presentations may be absent. The most frequently noted CT findings were alveolar or interstitial pulmonary edema (52%), pleural effusions (44%), and small pulmonary nodular densities (39%), which probably represented pulmonary vessels, collections of lung edema, and granulomata. Most surprisingly was the 35% incidence of mediastinal adenopathy. Slanetz et al3 recently described mediastinal ade-
100 THE AMERICAN JOURNAL OF CARDIOLOGY姞
VOL. 86
nopathy in 54% of patients with New York Heart Association class II to IV heart failure symptoms. Our incidence of enlarged mediastinal nodes was actually somewhat lower than might have been expected in this group with chronic, severe heart failure. Precarinal nodes were most frequently enlarged. Lymph node size typically fell below 1 cm, but occasional nodes approached 2 cm in diameter. Aggressive diuresis and tailoring of medical therapy to lower filling pressures failed to decrease lymph node size in the small subset of patients who underwent repeat CT imaging. Reactive lymphadenopathy with abundant plump histiocytes was demonstrated in patients who underwent biopsy. Unfortunately, biopsy resulted in 1 perioperative death. Although small (0.5 to 1.5 cm), mediastinal nodes may be commonly observed, more extensive adenopathy should prompt consideration of other potential etiologies such as infection or neoplasia. Study limitations include lack of simultaneous hemodynamic measurements and CT imaging, modest sample size, and lack of serial CT studies to assess the influence of waxing and waning of heart failure on key CT findings. Further, only a limited number of mediastinal nodes underwent biopsy, so the conclusion that all such nodes represent “reactive changes” must be interpreted cautiously. Finally, these results may overrepresent the number of CT abnormalities present in an advanced heart failure population because of selection bias, and should not be extrapolated to less symptomatic heart failure patients. Mediastinal adenopathy was observed in 35% of patients with chronic heart failure who underwent chest CT imaging. Clinical awareness that modest mediastinal adenopathy is common in patients with advanced heart failure may obviate the need for more invasive diagnostic evaluation in most patients undergoing transplant evaluation. 1. Primack SL, Muller NL, Mayo JR, Remy-Jardin M, Remy J. Pulmonary
parenchymal abnormalities of vascular origin:high resolution CT findings. Radiographics 1994;14:739 – 46. 2. Webb WR, Muller NL, Naidich DP. High-resolution CT Imaging of the Lung. New York: Raven Press. 1996:46 – 47, 220 –22. 3. Slanetz PJ, Truong M, Shepard JO, Trotman-Dickenson B, Drucker E, McCloud TC. Mediastinal lymphadenopathy and hazy mediastinal fat: new CT findings of congestive heart failure. Am J Radiol; in press.
JULY 1, 2000
12. Szokodi I, Kinnunen P, Weckstrom M, Toth M, Ruskoaho H. Evidence for
cAMP-dependent mechanisms mediating the effects of adrenomedullin, a new inotropic peptide. Circulation 1998;97:1062–1070. 13. Nagaya N, Nishikimi T, Okano Y, Uematsu M, Satoh T, Kyotani S, Kuribayashi S, Hamada S, Kakishita M, Nakanishi N, Takamiya M, Kunieda T, Matsuo H, Kangawa K. Plasma brain natriuretic peptide levels increase in proportion to the extent of right ventricular dysfunction in pulmonary hypertension. J Am Coll Cardiol 1998;31:202–208. 14. Nakamura M, Yoshida H, Funakoshi T, Arakawa N, Hiramori K. Renal, hemodyanmic and hormonal interactions between atrial natriuretic factor and arginine vasopressin in patients with congestive heart failure. Clin Sci 1992;82: 363–368. 15. Hirata Y, Hayakawa H, Suzuki Y, Suzuki E, Ikenouchi H, Kohmoto O, Kimura K, Kitamura K, Eto T, Kangawa K, Matsuo H, Omae M. Mechanisms of adrenomedullin-induced vasodilation in the rat kidney. Hypertension 1995;25: 790 –795. 16. Fukuhara M, Tsuchihashi T, Abe I, Fujishima M. Cardiovascular and neurohormonal effects of intravenous adrenomedullin in conscious rabbits. Am J Physiol 1995;269:R1289 –R1293. 17. Lainchbury JG, Nicholls MG, Espiner EA, Yandle TG, Lewis LK, Richards AM. Bioactivity and interactions of adrenomedullin and brain natriuretic peptide in patients with heart failure. Hypertension 1999;34:70 –75. 18. Edwards RM, Trixna W, Stack E, Aiyar N. Effect of adrenomedullin on cAMP levels along the rat nephron: comparison with CGRP. Am J Physiol 1996;271:F895–F899. 19. Brenner BM, Ballermann BJ, Gunning ME, Zeidel ML. Diverse biological actions of natriuretic peptide. Physiol Rev 1990;70:665– 699. 20. Yamaguchi T, Baba K, Doi Y, Yano K. Effect of adrenomedullin on aldosterone secretion by dispersed rat adrenal zona glomerulosa cells. Life Sci 1995;56:379 –387.
The Spectrum of Pulmonary Abnormalities on Computed Chest Tomographic Imaging in Patients With Advanced Heart Failure Sami Lewin,
BS,
Lee Goldberg,
MD, MPH,
valuation of potential candidates for heart transplantation involves extensive diagnostic testing E that occasionally includes computed tomographic (CT) imaging of the chest. Radiologic finding on chest computed tomography of acute pulmonary edema have been described and include smooth septal thickening, “ground glass” opacities, alveolar consolidation, vascular redistribution, pleural effusions, and cardiomegaly.1,2 Mediastinal lymphadenopathy has also recently been described.3 Prior studies have focused on CT studies obtained to assess noncardiac conditions and have not described findings specifically associated with a chronic heart failure population. •••
The study cohort was selected from ⬎400 consecutive patients referred to the Heart Failure and Cardiac Transplantation Service of the Massachusetts General Hospital between January 1, 1992, and June 1, 1998, for inpatient cardiac transplantation evaluation. Chest CT imaging studies were ordered at the discretion of From the Heart Failure and Transplantation Service, Division of Cardiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; University of Buffalo School of Medicine, Buffalo, New York; and Cardiology Division, University of Pennsylvania, Philadelphia, Pennsylvania. Dr. Dec’s address is: Heart Failure and Transplantation Center, Massachusetts General Hospital, Bigelow 645 Fruit Street, Boston, Massachusetts 02114. E-mail: [email protected]. Manuscript received November 10, 1999; revised manuscript received and accepted January 12, 2000.
98
©2000 by Excerpta Medica, Inc. All rights reserved. The American Journal of Cardiology Vol. 86 July 1, 2000
and G. William Dec,
MD
the attending transplant cardiologist and were usually obtained in patients who have had abnormal chest x-rays, markedly abnormal pulmonary function tests (forced expiratory volume in 1 second, vital capacity, or corrected diffusion capacity ⬍50% of predicted for age), a known pulmonary illness such as sarcoidosis or obstructive lung disease, unexplained pulmonary hypertension, or risk factors for lung malignancy. From a medical records review, we identified 71 patients who had a chest CT scan recorded as a part of their pretransplant evaluation. CT scans were reviewed with a board-certified chest radiologist to determine the nature and frequency of abnormal findings associated with chronic heart failure. The presence, size, and location of mediastinal lymph nodes were evaluated. Lymph nodes ⬎1 cm in diameter were considered physiologically abnormal. Demographic data including age, sex, diagnosis, duration of symptoms, prior chest surgery, New York Heart Association class, and history of smoking were included in the analysis. Right-sided cardiac catheterization and hemodynamic assessment were performed via the right internal jugular vein in all but 1 pediatric patient. CT scans were performed using standard institutional protocol without administration of intravenous contrast on a 9800 scanner (General Electric Medical Systems, Milwaukee, Wisconsin)3 All descriptive data are given as mean ⫾ 1 SD. 0002-9149/00/$–see front matter PII S0002-9149(00)00837-7
TABLE I Patient Characteristics and Hemodynamics
TABLE II Findings on CT Imaging of the Chest in Advanced Heart Failure
Parameter Age (ys) Gender Men Women Heart failure etiology Ischemic Dilated Valvular Other Smoking history Duration of symptoms (wks) Prior thoracic surgery Left ventricular ejection fraction New York Heart Association class II III IV Resting hemodynamics Right atrial pressure (mmHg) Pulmonary artery septolic pressure (mmHg) Mean pulmonary artery pressure (mmHg) Pulmonary artery diastolic pressure (mmHg) Mean pulmonary capillary wedge pressure (mm Hg) Cardiac index (L/min/m2)
52 ⫾ 10 77% 23% 48% 38% 4% 10% 63% 172 ⫾ 230 24% 21% ⫾ 8% 10% 53% 37% 10 51 35 25 23
⫾ ⫾ ⫾ ⫾ ⫾
7 20 12 10 10
2.1 ⫾ 0.6
Values are expressed mean ⫾ SEM.
Unpaired Student’s t test and Fisher’s exact test were used to compare differences in variables between groups. Multiple variable analysis was performed using logistic regression modeling (SAS Institute, Cary, North Carolina). The outcome of interest was defined as lymph nodes ⬎1 cm. The model simultaneously controlled for mean pulmonary capillary wedge pressure, age, sex, and smoking history. The mean ⫾ SD age of the study population was 52 ⫾ 10 years; there were 17 women and 54 men (Table I). Heart failure etiology was divided between ischemic heart disease and idiopathic dilated cardiomyopathy (Table I). Although the average duration of heart failure exceeded 3 years, symptoms ranged from ⬍1 week to ⬎20 years. Most patients had New York Heart Association functional class III or IV symptoms consistent with their referral for transplant evaluation. Resting hemodynamics confirmed chronic heart failure with mean pulmonary capillary wedge pressure ⬎20 mm Hg and cardiac index ⬍2.2 L/min/m2 despite optimal diuretic and vasodilator therapy (Table I). Chest CT scans were obtained in 6 patients because of a prior history of “cured” malignancy that included non-Hodgkin’s lymphoma (n ⫽ 2), childhood sarcoma (n ⫽ 1), colonic carcinoma in situ (n ⫽ 1), breast carcinoma (n ⫽ 1), and prostate carcinoma (n ⫽ 1). Four additional patients underwent evaluation for known granulomatous disease: systemic sarcoidosis (n ⫽ 3), treated tuberculosis (n ⫽ 1). Three other patients had undergone previous lobectomy and underwent CT imaging to better define their pulmonary anatomy. Most patients (n ⫽ 58) had parenchymal abnormalities on admission chest x-ray film (n ⫽ 22),
CT Finding* Pulmonary edema “Ground glass” appearance Alveolar edema Interstitial edema Reticulonodular pattern Pleural effusion Bilateral Right sided Left sided Pulmonary nodules Discrete Multiple Calcification Granulomatous Lymphadenopathy Atelectasis Emphysema Interstitial fibrosis Radiation induced Amiodarone Diffuse Focal consolidation /pneumonia Pulmonary venous redistribution Pulmonary arterial enlargement Other Bronchiectasis Cavitary lesion Foreign body (bullet) Lobectomy Normal
Patients 37 18 12 4 3 31 16 7 8 28 4 12 2 10 25 20 19 7 3 1 3 6 7 9 7 2 1 1 3 0
(52%) (25%) (17%) (6%) (4%) (44%) (28)%) (10%) (11%) (39%) (6%) (17%) (3%) (14%) (35%) (28%) (27%) (10%) (4%) (1%) (4%) (8%) (10%) (13%) (10%) (3%) (1%) (1%) (4%) (0%)
*Findings add up to ⬎100% because many patients had multiple findings.
TABLE III Location of Mediastinal Adenopathy in Patients With Advanced Heart Failure
Location of Nodes Precarinal Pretracheal Paratracheal Prevascular Subcarinal
No. of Patients (n ⫽ 25) and Overall %* 12 6 4 9 7
(48%) (24%) (16%) (36%) (28%)
*The percentage of patients who had at least 1 lymph node ⬎1 cm on CT imaging in that region.
prominent pulmonary arteries (n ⫽ 8), or impairment of pulmonary function tests exceeding that typically observed in patients with chronic heart failure (n ⫽ 28). One or more CT abnormalities were noted in all 71 patients (Table II). Pleural effusions were quite common (44%) and were most often observed bilaterally. A “ground glass” appearance was seen in 25% of patients and prominent alveolar edema was noted in 17% of cases. Pulmonary nodules were common (39%) and displayed a variety of patterns ranging from discrete nodules and multiple scattered granulomata to a diffuse reticulonodular pattern (Table II). Nodule size was typically 3 to 5 mm but could reach ⱖ10 mm. Calcium was quite uncommon. Mediastinal lymph nodes were absent in 27 patients (38%). NineBRIEF REPORTS
99
teen patients (27%) had nonpathologic lymph nodes (⬍1 cm along the short axis); the remaining 25 patients (35%) had ⱖ1 node ⬎1 cm in size. Lymphadenopathy did not exceed 2 cm in any patient. The locations of the enlarged lymph nodes are summarized in Table III. Nodal calcification was quite uncommon and seen in only 2.8% of cases. Repeat CT imaging was performed in 9 patients with visible lymphadenopathy. No change was noted in the extent or location of these nodes on repeat CT imaging. Lymph node biopsy was performed in 3 of the 5 patients with multiple mediastinal nodes (⬎1 cm). A prominent reactive histiocytic infiltrate was present in each case. In a multiple logistic regression that examined the effect of age, gender, resting pulmonary capillary wedge pressure, smoking history, and a history of granulomatous disease, no significant predictors for lymphadenopathy were identified. •••
CT findings did not preclude listing in any patient. However, 1 patient developed hemodynamic instability and died of multiorgan failure 48 hours after biopsy. A second patient developed lung adenocarcinoma 18 months after transplantation. Seven months before transplantation, a single 1-cm subcarinal lymph node was noted. Repeat CT imaging disclosed the interim development of 1- to 2.5-cm lymph nodes in the left internal mammary chain and a new mediatinal mass. The subcarinal node was no longer evident. The remaining 19 transplant recipients remain free of malignancy or active infection. CT findings in populations with chronic heart failure have not been previously described. It is well known that chronic heart failure leads to enhanced lymphatic drainage of the pulmonary parenchyma as a compensatory mechanism for chronic elevation in left-sided filling pressures. Hence, the typical CT findings seen during acute heart failure presentations may be absent. The most frequently noted CT findings were alveolar or interstitial pulmonary edema (52%), pleural effusions (44%), and small pulmonary nodular densities (39%), which probably represented pulmonary vessels, collections of lung edema, and granulomata. Most surprisingly was the 35% incidence of mediastinal adenopathy. Slanetz et al3 recently described mediastinal ade-
100 THE AMERICAN JOURNAL OF CARDIOLOGY姞
VOL. 86
nopathy in 54% of patients with New York Heart Association class II to IV heart failure symptoms. Our incidence of enlarged mediastinal nodes was actually somewhat lower than might have been expected in this group with chronic, severe heart failure. Precarinal nodes were most frequently enlarged. Lymph node size typically fell below 1 cm, but occasional nodes approached 2 cm in diameter. Aggressive diuresis and tailoring of medical therapy to lower filling pressures failed to decrease lymph node size in the small subset of patients who underwent repeat CT imaging. Reactive lymphadenopathy with abundant plump histiocytes was demonstrated in patients who underwent biopsy. Unfortunately, biopsy resulted in 1 perioperative death. Although small (0.5 to 1.5 cm), mediastinal nodes may be commonly observed, more extensive adenopathy should prompt consideration of other potential etiologies such as infection or neoplasia. Study limitations include lack of simultaneous hemodynamic measurements and CT imaging, modest sample size, and lack of serial CT studies to assess the influence of waxing and waning of heart failure on key CT findings. Further, only a limited number of mediastinal nodes underwent biopsy, so the conclusion that all such nodes represent “reactive changes” must be interpreted cautiously. Finally, these results may overrepresent the number of CT abnormalities present in an advanced heart failure population because of selection bias, and should not be extrapolated to less symptomatic heart failure patients. Mediastinal adenopathy was observed in 35% of patients with chronic heart failure who underwent chest CT imaging. Clinical awareness that modest mediastinal adenopathy is common in patients with advanced heart failure may obviate the need for more invasive diagnostic evaluation in most patients undergoing transplant evaluation. 1. Primack SL, Muller NL, Mayo JR, Remy-Jardin M, Remy J. Pulmonary
parenchymal abnormalities of vascular origin:high resolution CT findings. Radiographics 1994;14:739 – 46. 2. Webb WR, Muller NL, Naidich DP. High-resolution CT Imaging of the Lung. New York: Raven Press. 1996:46 – 47, 220 –22. 3. Slanetz PJ, Truong M, Shepard JO, Trotman-Dickenson B, Drucker E, McCloud TC. Mediastinal lymphadenopathy and hazy mediastinal fat: new CT findings of congestive heart failure. Am J Radiol; in press.
JULY 1, 2000