Cited by 2,582Heart Failure Treatment and ManagementCardiac Fibrosis and RemodelingNutrition and Health in Aging

The DOI matches its Crossref record; 55 of the 55 references it cites were found in a registry or an index.

Elevated Circulating Levels of Tumor Necrosis Factor in Severe Chronic Heart Failure

Open access

Levine, Beth, Kalman, Jill, Mayer, Lloyd, Fillit, Howard M., Packer, Milton·1990·New England Journal of Medicine

DOI 10.1056/nejm199007263230405

Open this paper in CoChat — free account Open PDF

Abstract

BACKGROUND AND METHODS: Although cachexia often accompanies advanced heart failure, little is known about the causes of the cachectic state. To assess the potential role of tumor necrosis factor in the pathogenesis of cardiac cachexia, we measured serum levels of the factor in 33 patients with chronic heart failure, 33 age-matched healthy controls, and 9 patients with chronic renal failure. RESULTS: Mean (+/- SEM) serum levels of tumor necrosis factor were higher in the patients with heart failure (115 +/- 25 U per milliliter) than in the healthy controls (9 +/- 3 U per milliliter; P less than 0.001). Nineteen of the patients with chronic heart failure had serum levels of tumor necrosis factor greater than or equal to 39 U per milliliter (greater than 2 SD above the mean value for the control group), whereas the remaining 14 patients had serum levels of tumor necrosis factor below this level. The patients with high levels of tumor necrosis factor were more cachectic than those with low levels (82 +/- 3 vs. 95 +/- 6 percent of ideal body weight, respectively; P less than 0.05) and had more advanced heart failure, as evidenced by their higher values for plasma renin activity (2.92 +/- 0.53 vs. 1.06 +/- 0.53 ng per liter per second [10.5 +/- 1.9 vs. 3.8 +/- 1.9 ng per milliliter per hour]; P less than 0.01) and lower serum sodium concentration (135 +/- 1 vs. 138 +/- 1 mmol per liter; P less than 0.05). The group with high levels of tumor necrosis factor also had lower hemoglobin levels (7.82 +/- 0.2 vs. 8.69 +/- 0.4 mmol per liter [12.6 +/- 0.4 vs. 14.0 +/- 0.6 g per deciliter]) and higher values for blood urea nitrogen (19.5 +/- 2.2 vs. 12.5 +/- 1.8 mmol per liter) than the group with low levels of tumor necrosis factor (P less than 0.05 for both). The high levels of tumor necrosis factor were not due solely to decreased renal clearance, however, since the levels in the patients with heart failure were considerably higher than those in the nine patients with chronic renal failure (115 +/- 25 vs. 45 +/- 25 U per milliliter; P less than 0.05). CONCLUSIONS: These findings indicate that circulating levels of tumor necrosis factor are increased in cachectic patients with chronic heart failure and that this elevation is associated with the marked activation of the renin-angiotensin system seen in patients with end-stage cardiac disease.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Integrity signals

Registry

Crossref · 10.1056/nejm199007263230405

Cites

55 of 55 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays
Mosmann, T. (1983) · Journal of Immunological Methods · doi:10.1016/0022-1759(83)90303-4 · Cited by 56,104
T Cell Growth Factor: Parameters of Production and a Quantitative Microassay for Activity
Gillis, S. A., Ferm, M. M., Ou, W., & Smith, K. A. (1978) · The Journal of Immunology · doi:10.4049/jimmunol.120.6.2027 · Cited by 3,273
Shock and Tissue Injury Induced by Recombinant Human Cachectin
Tracey, K. J., Beutler, B., Lowry, S. F., Merryweather, J., Wolpe, S., Milsark, I. W., Hariri, R. J., Fahey, T. J., Zentella, A., Albert, J. D., et al. (1986) · Science · doi:10.1126/science.3764421 · Cited by 2,549
Tumor necrosis factor and interleukin 1: cytokines with multiple overlapping biological activities.
Le, J., & Vilček, J. (1987) · PubMed · Cited by 1,327
Diseases of the heart
Friedberg, C. K. (1966) · Biblioteca Digital (Real Academia Nacional de Medicina) · Cited by 1,308
ASSOCIATION BETWEEN TUMOUR NECROSIS FACTOR IN SERUM AND FATAL OUTCOME IN PATIENTS WITH MENINGOCOCCAL DISEASE
Waage, A., Halstensen, A. I., & Espevik, T. (1987) · The Lancet · doi:10.1016/s0140-6736(87)91728-4 · Cited by 1,085
Cachectin/tumor necrosis factor: production, distribution, and metabolic fate in vivo.
Beutler, B., Milsark, I. W., & Cerami, A. (1985) · The Journal of Immunology · doi:10.4049/jimmunol.135.6.3972 · Cited by 771
Tumor Necrosis Factor and Interleuktn-1 in the Serum of Children with Severe Infectious Purpura
Girardin, E. P., Grau, G. E., Dayer, J., Roux-Lombard, P., the J5 Study Group*, & Lambert, P.-H. (1988) · New England Journal of Medicine · doi:10.1056/nejm198808183190703 · Cited by 737
Cachectin/tumor necrosis factor induces cachexia, anemia, and inflammation.
Tracey, K. J., He, W., Manogue, K. R., Fong, Y., HESSE, D. G., Nguyen, H. T., Kuo, G. C., Beutler, B., Cotran, R. S., & Cerami, A. (1988) · The Journal of Experimental Medicine · doi:10.1084/jem.167.3.1211 · Cited by 730
Elevated levels of circulating cachectin/tumor necrosis factor in patients with acquired immunodeficiency syndrome
Lähdevirta, J., Maury, C. P. J., Teppo, A., & Repo, H. (1988) · The American Journal of Medicine · doi:10.1016/0002-9343(88)90576-1 · Cited by 717

Show all 55 references

Research works printed but not linked: 4

Packer, 1987, Circulation, 75, IV-80
Bertani, 1989, Am J Pathol, 134, 419
Pessina, 1987, Lymphokine Res, 6, 35
Le, 1987, Lab Invest, 56, 234

Sorted by citations

Items 501–600 of 1,003

Insulin resistance and cardiovascular disease
Egan, B. M. (2001) · American Journal of Hypertension · doi:10.1016/s0895-7061(01)02078-7 · Cited by 98
Blockade of NF-κB improves cardiac function and survival without affecting inflammation in TNF-α-induced cardiomyopathy
Kawamura, N., KUBOTA, T., KAWANO, S., Monden, Y., Feldman, A. M., Tsutsui, H., Takeshita, A., & Sunagawa, K. (2005) · Cardiovascular Research · doi:10.1016/j.cardiores.2005.02.007 · Cited by 99
“patients with congestive heart failure [2,3].”
Pathophysiology and treatment of inflammatory anorexia in chronic disease
Braun, T. P., & Marks, D. L. (2010) · Journal of Cachexia Sarcopenia and Muscle · doi:10.1007/s13539-010-0015-1 · Cited by 108
“In chronic heart failure, circulating levels of tumor necrosis factor (TNF) [10–12] and interleukin-6 (IL-6) [11] are increased, and correlate with the degree of exercise impairment in these patients.”
Background
Cholinergic Activity as a New Target in Diseases of the Heart
Roy, A., Guatimosim, S., Prado, V. F., Gros, R., & Prado, M. A. M. (2014) · Molecular Medicine · doi:10.2119/molmed.2014.00125 · Cited by 102
Amiodarone Inhibits Production of Tumor Necrosis Factor-α by Human Mononuclear Cells
Matsumori, A., Ono, K., Nishio, R., Nose, Y., & Sasayama, S. (1997) · Circulation · doi:10.1161/01.cir.96.5.1386 · Cited by 99
Role of TNF in Mediating Renal Insufficiency Following Cardiac Surgery: Evidence of a Postbypass Cardiorenal Syndrome
Meldrum, D. R., & DONNAHOO, K. K. (1999) · Journal of Surgical Research · doi:10.1006/jsre.1999.5660 · Cited by 99
“TNF provokes glomerular and renal disease [23, 50, 3–62].”
Background
Anti–tumor necrosis factor α therapy and heart failure: What have we learned and where do we go from here?
Khanna, D., McMahon, M. A., & Furst, D. E. (2004) · Arthritis & Rheumatism · doi:10.1002/art.20164 · Cited by 98
The Ca2+-Sensitizer Levosimendan Improves Oxidative Damage, BNP and Pro-Inflammatory Cytokine Levels in Patients with Advanced Decompensated Heart Failure in Comparison to Dobutamine
Avgeropoulou, C., Andreadou, I., Markantonis‐Kyroudis, S., Demopoulou, M., MISSOVOULOS, P., Androulakis, A., & Kallikazaros, I. E. (2005) · European Journal of Heart Failure · doi:10.1016/j.ejheart.2005.02.002 · Cited by 98
Direct comparison of serial B-type natriuretic peptide and NT-proBNP levels for prediction of short- and long-term outcome in acute decompensated heart failure
Noveanu, M., Breidthardt, T., Potocki, M., Reichlin, T., Twerenbold, R., Uthoff, H., Socrates, T., Arenja, N., Reiter, M., Meissner, J., et al. (2011) · Critical Care · doi:10.1186/cc9398 · Cited by 98
“TNF and inflammatory cytokines may contribute to myocardial damage and thus to a higher mortality [41,42].”
Background
Chronic heart failure and skeletal muscle catabolism: effects of exercise training
Schulze, P. C., Gielen, S., Schuler, G. C., & Hambrecht, R. (2002) · International Journal of Cardiology · doi:10.1016/s0167-5273(02)00243-7 · Cited by 98
Endothelial function in congestive heart failure
Drexler, H., Hayoz, D., Münzel, T. F., Just, H., ZELIS, R. F., & Brunner, H. R. (1993) · American Heart Journal · doi:10.1016/0002-8703(93)90926-z · Cited by 98
Insulin: An endogenous cardioprotector
Das, U. N. (2003) · Current Opinion in Critical Care · doi:10.1097/00075198-200310000-00007 · Cited by 97
The pathophysiology of advanced heart failure
Baig, M. K., Mahon, N., McKenna, W. J., Caforio, A. L. P., Bonow, R. O., Francis, G. S., & Gheorghiade, M. (1998) · American Heart Journal · doi:10.1016/s0002-8703(98)70252-2 · Cited by 97
Statin use and survival in patients with chronic heart failure — results from two observational studies with 5200 patients
Anker, S. D., Clark, A. L., Winkler, R., Zugck, C., Cicoira, M., Ponikowski, P. P., Davos, C. H., Banasiak, W., Zardini, P., Haass, M., et al. (2006) · International Journal of Cardiology · doi:10.1016/j.ijcard.2006.03.057 · Cited by 97
Peripheral Muscle Dysfunction in Chronic Obstructive Pulmonary Disease
Maltais, F., Leblanc, P., Jobin, J., & Casaburi, R. H. (2000) · Clinics in Chest Medicine · doi:10.1016/s0272-5231(05)70176-3 · Cited by 92
Muscular levels of proinflammatory cytokines correlate with a reduced expression of insulinlike growth factor-I in chronic heart failure
Schulze, P. C., Gielen, S., Adams, V., Linke, A. H.-P., Möbius‐Winkler, S., Erbs, S., Kratzsch, J., Hambrecht, R., & Schuler, G. C. (2003) · Basic Research in Cardiology · doi:10.1007/s00395-003-0411-1 · Cited by 97
“Serum GH induces the local IGF-I expression mediated through the GH receptor (24), a regulatory mechanism which at least in part is impaired in CHF due to a peripheral GH resistance (3, 29). In addition, skeletal muscle IGF-I expression is modulated in response to alterations in muscle use (12) and it has been shown t…”
Background
Elevated interleukin-6 levels in patients with asymptomatic left ventricular systolic dysfunction
Raymond, R. J., DEHMER, G. J., Theoharides, T. C., & Deliargyris, E. (2001) · American Heart Journal · doi:10.1067/mhj.2001.113078 · Cited by 97
Anti–Tumor Necrosis Factor-α Antibody Limits Heart Failure in a Transgenic Model
Kadokami, T., Frye, C. B., Lemster, B. H., Wagner, C. L., Feldman, A. M., & McTiernan, C. F. (2001) · Circulation · doi:10.1161/hc3501.096063 · Cited by 97
Effect of partial fatty acid oxidation inhibition with trimetazidine on mortality and morbidity in heart failure: Results from an international multicentre retrospective cohort study
Fragasso, G., Rosano, G. M. C., Baek, S. H., Sisakian, H. S., Napoli, P. D., Alberti, L., Calori, G., Kang, S., Sahakyan, L. G., Sanosyan, A., et al. (2012) · International Journal of Cardiology · doi:10.1016/j.ijcard.2012.09.123 · Cited by 96
“The relationship between high metabolic rate and heart failure can be explained by increased myocardial oxygen consumption, metabolic cost of breathing, increased sympathetic tone, and higher circulating levels of tumor necrosis factor and other pro-inflammatory cytokines [36–40].”
Background
The Role of TNF-α as a Proinflammatory Cytokine in Pathological Processes
Silva, L. B., Neto, A. P. D. S., Maia, S. M. A. S., Guimarães, C. D. S., Quidute, I. L., Carvalho, A. D. A. T., Alves, S., & Leão, J. C. (2019) · The Open Dentistry Journal · doi:10.2174/1874210601913010332 · Cited by 105
Leukocytosis and adverse hospital outcomes after acute myocardial infarction
Menon, V., Lessard, D., Yarzebski, J., Furman, M. I., Gore, J. M., & Goldberg, R. J. (2003) · The American Journal of Cardiology · doi:10.1016/s0002-9149(03)00651-9 · Cited by 96
PPAR gamma protects cardiomyocytes against oxidative stress and apoptosis via Bcl-2 upregulation
Ren, Y., Sun, C., Sun, Y., Tan, H., Wu, Y., Cui, B., & Wu, Z. (2009) · Vascular Pharmacology · doi:10.1016/j.vph.2009.06.004 · Cited by 96
Impaired tissue responsiveness to organic nitrates and nitric oxide: A new therapeutic frontier?
Chirkov, Y. Y., & Horowitz, J. D. (2007) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2007.06.012 · Cited by 96
Microglia activation in the hypothalamic PVN following myocardial infarction
Rana, I., Stebbing, M. J., Kompa, A. R., Kelly, D. J., Krum, H., & Badoer, E. (2010) · Brain Research · doi:10.1016/j.brainres.2010.02.028 · Cited by 95
“Following a myocardial infarct there is activation of the immune system, and proinflammatory cytokines such as TNF-α, IL-6 and IL-1β are increased in the heart (Levine et al., 1990).”
BackgroundInfluential
Blockade of NF-κB ameliorates myocardial hypertrophy in response to chronic infusion of angiotensin II
KAWANO, S., KUBOTA, T., Monden, Y., Kawamura, N., Tsutsui, H., Takeshita, A., & Sunagawa, K. (2005) · Cardiovascular Research · doi:10.1016/j.cardiores.2005.04.030 · Cited by 96
“Second, plasma levels as well as myocardial expression of proinflammatory cytokines, including TNF-a, are increased in patients with heart failure [4,5].”
Background
Modulation of Cytokine Production and Protection Against Lethal Endotoxemia by the Cardiac Glycoside Ouabain
Matsumori, A., Ono, K., Nishio, R., Igata, H., Pharm, B., Shioi, T., Matsui, S., Furukawa, Y., Iwasaki, A., Nose, Y., et al. (1997) · Circulation · doi:10.1161/01.cir.96.5.1501 · Cited by 96
Serum interleukin-6 in congestive heart failure secondary to idiopathic dilated cardiomyopathy
Roig, E. S., Orús, J., Paré, C., Azqueta, M., Filella, X., Pérez‐Villa, F., Heras, M., & Sanz, G. (1998) · The American Journal of Cardiology · doi:10.1016/s0002-9149(98)00388-9 · Cited by 96
Heart failure and anti tumor necrosis factor-alpha in systemic chronic inflammatory diseases
Sinagra, E., Perricone, G., Romano, C., & Cottone, M. (2013) · European Journal of Internal Medicine · doi:10.1016/j.ejim.2012.12.015 · Cited by 95
“Pro-inflammatory cytokines, including TNF-alpha, do not only contribute to the pathogenesis of RA, but also mediate endothelial dysfunction, vascular instability, and atherosclerosis progression [7,23,46].”
Background
Interleukin-1β Inhibits Phospholamban Gene Expression in Cultured Cardiomyocytes
McTiernan, C. F., Lemster, B. H., Frye, C. B., Brooks, S. S., Combes, A., & Feldman, A. M. (1997) · Circulation Research · doi:10.1161/01.res.81.4.493 · Cited by 95
Targeting Inflammation in Heart Failure with Histone Deacetylase Inhibitors
McKinsey, T. A. (2011) · Molecular Medicine · doi:10.2119/molmed.2011.00022 · Cited by 95
Markers of fibrosis, inflammation, and remodeling pathways in heart failure
Passino, C., Barison, A., Vergaro, G., Gabutti, A., Borrelli, C., Emdin, M., & Clerico, A. (2014) · Clinica Chimica Acta · doi:10.1016/j.cca.2014.09.006 · Cited by 99
“[23] reported for the first time that HF patients usually show elevated circulating levels of tumor necrosis factor (TNF).”
Background
Cytokines in acute rheumatic fever
Yeğin, O., Coşkun, M., & Ertuğ, H. (1996) · European Journal of Pediatrics · doi:10.1007/s004310050545 · Cited by 94
Ghrelin improves left ventricular dysfunction and cardiac cachexia in heart failure
Nagaya, N. (2003) · Current Opinion in Pharmacology · doi:10.1016/s1471-4892(03)00013-4 · Cited by 92
Experimental Autoimmune Myocarditis Produced by Adoptive Transfer of Splenocytes After Myocardial Infarction
Maisel, A. S., Cesario, D. A., Baird, S. M., Rehman, J., Haghighi, P., & Carter, S. M. (1998) · Circulation Research · doi:10.1161/01.res.82.4.458 · Cited by 93
Altered expression of myosin heavy chain in human skeletal muscle in chronic heart failure
Sullivan, M. J., Duscha, B. D., Klitgaard, H., Kraus, W. E., Cobb, F. R., & Saltin, B. (1997) · Medicine & Science in Sports & Exercise · doi:10.1097/00005768-199707000-00004 · Cited by 93
Inflammatory Cytokines in Chronic Heart Failure: Interleukin-8 is Associated with Adverse Outcome. Results from CORONA
Nymo, S. H., Hulthe, J., Ueland, T., McMurray, J. J. V., Wikstrand, J., Askevold, E. T., Yndestad, A., Gullestad, L. L., & Aukrust, P. (2013) · European Journal of Heart Failure · doi:10.1093/eurjhf/hft125 · Cited by 94
An overview of tumor necrosis factor α and the failing human heart
Torre‐Amione, G., Bozkurt, B., Deswal, A. M., & Mann, D. L. (1999) · Current Opinion in Cardiology · doi:10.1097/00001573-199905000-00003 · Cited by 93
A20 (TNFAIP3) Alleviates CVB3-Induced Myocarditis via Inhibiting NF-κB Signaling
Gui, J., Yue, Y., Chen, R., Xu, W., & Xiong, S. (2012) · PLoS ONE · doi:10.1371/journal.pone.0046515 · Cited by 92
TNFR2 Stimulation Promotes Mitochondrial Fusion via Stat3- and NF-kB–Dependent Activation of OPA1 Expression
Nan, J., Hu, H., Sun, Y., Zhu, L., Wang, Y., Zhong, Z., Zhao, J., Zhang, N., Wang, Y., Wang, Y., et al. (2017) · Circulation Research · doi:10.1161/circresaha.117.311143 · Cited by 92
Dilated cardiomyopathy and mitochondrial dysfunction in Sirt1-deficient mice: A role for Sirt1-Mef2 in adult heart
Planavila, A., Domínguez, E., Navarro, M., Vinciguerra, M., Iglesias, R., Giralt, M., Lope‐Piedrafita, S., Ruberte, J., & Villarroya, F. (2012) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2012.07.019 · Cited by 92
“Next, we assessed gene expression for pro-inflammatory pathways which are known to exert an important role in most cardiac disease states [16,17].”
Method
Lack of association between polymorphisms of eight candidate genes and idiopathic dilated cardiomyopathy
Tiret, L., Mallet, C., Poirier, O., Nicaud, V., Millaire, A., Bouhour, J.-B., Roizès, G., Desnos, M., Dorent, R., Schwartz, K., et al. (2000) · Journal of the American College of Cardiology · doi:10.1016/s0735-1097(99)00522-7 · Cited by 92
The role of inflammation in heart failure: new therapeutic approaches.
Oikonomou, E. K., Tousoulis, D., Siasos, G., Zaromitidou, M., Papavassiliou, A. G., & Stefanadis, C. (2011) · PubMed · Cited by 91
Elevation of an endogenous inhibitor of nitric oxide synthesis in experimental congestive heart failure
Feng, Q. (1998) · Cardiovascular Research · doi:10.1016/s0008-6363(97)00242-3 · Cited by 91
ROLE OF BACTERIAL ENDOTOXIN IN CHRONIC HEART FAILURE
Charalambous, B. M., Stephens, R. C. M., Feavers, I. M., & Montgomery, H. (2007) · Shock · doi:10.1097/shk.0b013e318033ebc5 · Cited by 91
“Low-grade systemic inflammation is a feature of both acute and chronic heart failure (15), with elevation in circulating PIC levels (16), such as TNF-! (17), interleukin (IL)-6 (15), and IL-1 (18), being associated with worsening of symptoms, hospital readmission, and even mortality (19).”
Background
Production and Secretion of Adrenomedullin in Cultured Rat Cardiac Myocytes and Nonmyocytes: Stimulation by Interleukin-1β and Tumor Necrosis Factor-α**This work was supported in part by Special Coordination Funds for Promoting Science and Technology (Encouragement System of COE) from the Science and Technology Agency of Japan, the Ministry of Health and Welfare, and the Human Science Foundation of Japan.
Horio, T., Nishikimi, T., Yoshihara, F., Nagaya, N., Matsuo, H., Takishita, S., & Kangawa, K. (1998) · Endocrinology · doi:10.1210/endo.139.11.6306 · Cited by 91
TNFR1 and TNFR2 Signaling Interplay in Cardiac Myocytes
Defer, N., Azroyan, A., Pecker, F., & Pavoine, C. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m704003200 · Cited by 90
Activation of JNK and xanthine oxidase by TNF-α impairs nitric oxide-mediated dilation of coronary arterioles
ZHANG, C., Hein, T. I. A., WANG, W., REN, Y., Shipley, R. D., & Kuo, L. (2006) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2005.11.010 · Cited by 88
Secretory sphingomyelinase is upregulated in chronic heart failure: a second messenger system of immune activation relates to body composition, muscular functional capacity, and peripheral blood flow
Doehner, W., Bunck, A. C., Rauchhaus, M., von Haehling, S., Brunkhorst, F. M., Cicoira, M., Tschöpe, C., Ponikowski, P. P., Claus, R. A., & Anker, S. D. (2007) · European Heart Journal · doi:10.1093/eurheartj/ehl541 · Cited by 90
Molecular and Immune Mechanisms in the Pathogenesis of Cardiomyopathy
Matsumori, A. (1997) · Japanese Circulation Journal-english Edition · doi:10.1253/jcj.61.275 · Cited by 90
Circulatory Resuscitation With Left Ventricular Assist Device Support Reduces Interleukins 6 and 8 Levels
Goldstein, D. J., Moazami, N., Seldomridge, J. A., Laio, H., Ashton, R. C., Naka, Y., Pinsky, D. J., & Öz, M. C. (1997) · The Annals of Thoracic Surgery · doi:10.1016/s0003-4975(96)01117-4 · Cited by 90
“The cytokine milieu that accompanies chronic heart failure has been characterized [5, 10].”
Background
Neutrophil-to-Lymphocyte Ratio and Outcomes in Patients with New-Onset or Worsening Heart Failure with Reduced and Preserved Ejection Fraction
Curran, F. M., Bhalraam, U., Mohan, M., Singh, J. S., Anker, S. D., Dickstein, K., Doney, A. S. F., Filippatos, G. S., Casella, G., Metra, M., et al. (2021) · ESC Heart Failure · doi:10.1002/ehf2.13424 · Cited by 89
“There has been long-standing interest in the role of inflammation in the pathophysiology of heart failure (HF).(1) It has been shown that both heart with reduced ejection fraction (HFrEF) and heart with preserved ejection fraction (HFpEF) are associated with elevations in biomarkers related to inflammatory processes,…”
Background
Cytokine Response to Pulmonary Thromboendarterectomy
Langer, F., Schramm, R., Bauer, M. W., Tscholl, D., Kunihara, T., & Scha¨fers, H.-J. (2004) · CHEST Journal · doi:10.1378/chest.126.1.135 · Cited by 89
Activation of the Cardiac Interleukin-6 System in Advanced Heart Failure
Plenz, G., Fang, S. Z., Tjan, T. D. T., Carsten, K., Baba Hideo, A., Erren, M., Flesch, M., Thomas, W., Scheld, H. H., & Deng Mario, C. (2001) · European Journal of Heart Failure · doi:10.1016/s1388-9842(01)00137-4 · Cited by 89
Inappropriately low plasma leptin concentration in the cachexia associated with chronic heart failure
Murdoch, D., Rooney, E., Dargie, H. J., Shapiro, D., Morton, J. J., & McMurray, J. J. V. (1999) · Heart · doi:10.1136/hrt.82.3.352 · Cited by 89
“It is also possible that alterations in the synthesis or release of leptin, leading to its overproduction, may underlie the cachexia that often accompanies chronic medical conditions—for example chronic heart failure, which is characterised by selective loss of adipose tissue. We and others have reported that cachexia…”
Background
Coronary Microvascular Dysfunction and Diastolic Load Correlate With Cardiac Troponin T Release Measured by a Highly Sensitive Assay in Patients With Nonischemic Heart Failure
Takashio, S., Yamamuro, M., Izumiya, Y., Sugiyama, S., Kojima, S., Yamamoto, E., Tsujita, K., Tanaka, T., Tayama, S., Kaikita, K., et al. (2013) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2013.03.065 · Cited by 88
“Because inflammatory cytokines and oxidative stress increase with the progression of HF (25,26), the association between cTnT release and these factors might be applicable only to patients with advanced HF.”
Background
Exercise Training in Chronic Heart Failure: Effects on Pro-Inflammatory Markers
Niebauer, J., Clark, A. L., Webb-Peploe, K. M., & Coats, A. J. S. (2004) · European Journal of Heart Failure · doi:10.1016/j.ejheart.2004.07.012 · Cited by 88
Important factors other than dialysis adequacy associated with inadequate dietary protein and energy intakes in patients receiving maintenance peritoneal dialysis
Wang, A. Y.-M., Sanderson, J. E., Sea, M. M.-M., Wang, M., Lam, C. W.-K., Li, P. K., Lui, S., & Woo, J. (2003) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/77.4.834 · Cited by 88
“Demographic factors Male:female 53:51 86:76 Age (y) 53 ± 141 56 ± 11 Current or exsmoker (n [%]) 37 [36] 63 [39] Duration of dialysis (mo) 35 ± 27 39 ± 30 Renal diagnosis (n [%])2 Chronic glomerulonephritis 44 [42] 43 [27]3 Diabetic nephropathy 18 [17] 48 [30] Hypertensive nephrosclerosis 8 [8] 26 [16] Tubulointerstit…”
Cellular remodeling in heart failure disrupts KATP channel‐dependent stress tolerance
Hodgson, D. M., Zingman, L. V., Kane, G. C., Perez‐Terzic, C., Bienengraeber, M., Ozcan, C., Gumina, R. J., Pucar, D., O'Coclain, F., Mann, D. L., et al. (2003) · The EMBO Journal · doi:10.1093/emboj/cdg192 · Cited by 88
Myocardial gene expression of leukaemia inhibitory factor, interleukin‐6 and glycoprotein 130 in end‐stage human heart failure
Eiken, H. G., Øie, E., Damås, J. K., Yndestad, A., Bjerkeli, V., Aass, H., Simonsen, S., Geiran, O. R., Tønnessen, T., Christensen, G., et al. (2001) · European Journal of Clinical Investigation · doi:10.1046/j.1365-2362.2001.00795.x · Cited by 88
Effects of atorvastatin on reactive hyperemia and inflammatory process in patients with congestive heart failure
Tousoulis, D., Antoniades, C. A., Bosinakou, E., Kotsopoulou, M., Pitsavos, C. E., Vlachopoulos, C. V., Panagiotakos, D. B., & Stefanadis, C. (2004) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2004.08.037 · Cited by 88
The role of interferon-γ in cardiovascular disease: an update
Elyasi, A., Voloshyna, I., Ahmed, S., Kasselman, L. J., Behbodikhah, J., Leon, J. D., & Reiss, A. B. (2020) · Inflammation Research · doi:10.1007/s00011-020-01382-6 · Cited by 84
The Role of Inflammation in the Cardio-Renal Syndrome: A Focus on Cytokines and Inflammatory Mediators
Rosner, M. H., Ronco, C., & Okusa, M. D. (2012) · Seminars in Nephrology · doi:10.1016/j.semnephrol.2011.11.010 · Cited by 89
Emerging importance of chemokine receptor CXCR3 and its ligands in cardiovascular diseases
Altara, R., Manca, M., Brandão, R. D., Zeidan, A., Booz, G. W., & Zouein, F. A. (2016) · Clinical Science · doi:10.1042/cs20150666 · Cited by 87
Angiotensin converting enzyme inhibitors suppress production of tumor necrosis factor-α in vitro and in vivo
Fukuzawa, M., Satoh, J., Sagara, M., Muto, G., Muto, Y., Nishimura, S., Miyaguchi, S., Qiang, X., Sakata, Y., NAKAZAWA, T., et al. (1997) · Immunopharmacology · doi:10.1016/s0162-3109(96)00160-9 · Cited by 87
Pimobendan inhibits the production of proinflammatory cytokines and gene expression of inducible nitric oxide synthase in a murine model of viral myocarditis
Iwasaki, A., Matsumori, A., Yamada, T., Shioi, T., Wang, W., Ono, K., Nishio, R., Okada, M., & Sasayama, S. (1999) · Journal of the American College of Cardiology · doi:10.1016/s0735-1097(98)00692-5 · Cited by 87
Increased levels of serum neoprotein and decreased production of neutrophil superoxide anions in chronic heart failure with elevated levels of tumor necrosis factor-alpha
Wiedermann, C. J., Beimpold, H., Herold, M., Knapp, E., & Braunsteiner, H. (1993) · Journal of the American College of Cardiology · doi:10.1016/0735-1097(93)90776-w · Cited by 87
Cachexia: a therapeutic approach beyond cytokine antagonism
von Haehling, S., Genth‐Zotz, S., Anker, S. D., & Volk, H. (2002) · International Journal of Cardiology · doi:10.1016/s0167-5273(02)00245-0 · Cited by 85
Tumor Necrosis Factor-α–Induced Iron Sequestration and Oxidative Stress in Human Endothelial Cells
Nanami, M., Ookawara, T., Otaki, Y., Ito, K., Moriguchi, R., Miyagawa, K., Hasuike, Y., Izumi, M., Eguchi, H., Suzuki, K., et al. (2005) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.0000190610.63878.20 · Cited by 87
Beneficial effects of statins in patients with non-ischemic heart failure
Laufs, U., Waßmann, S., Schackmann, S., Heeschen, C., B�hm, M., & Nickenig, G. (2004) · Zeitschrift für Kardiologie · doi:10.1007/s00392-004-1005-0 · Cited by 86
“TNF , which has been implied in the pathogenesis and progression of heart failure (15), was reduced to half after statin treatment (Fig.”
Background
Myoglobin Protects the Heart from Inducible Nitric-oxide Synthase (iNOS)-mediated Nitrosative Stress
Gödecke, A., Molojavyi, A., Heger, J., Flögel, U., Ding, Z., Jacoby, C., & Schrader, J. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m302573200 · Cited by 86
Tumour Necrosis Factor in Chronic Heart Failure
Bolger, A. P., & Anker, S. D. (2000) · Drugs · doi:10.2165/00003495-200060060-00002 · Cited by 86
“Levine and coworkers[24] were the first to demonstrate that patients with severe CHF and cardiac cachexia had elevated plasma TNF levels and this finding was soon confirmed by others.”
Background
Tumor necrosis factor in myocardial hypertrophy and ischaemia — an anti-apoptotic perspective
Sack, M. N. (2000) · Cardiovascular Research · doi:10.1016/s0008-6363(99)00228-x · Cited by 86
The Cytokine Network in the Critically Ill
Bellomo, R. (1992) · Anaesthesia and Intensive Care · doi:10.1177/0310057x9202000303 · Cited by 85
Phase 3 DREAM-HF Trial of Mesenchymal Precursor Cells in Chronic Heart Failure
Borow, K. M., Yaroshinsky, A., Greenberg, B., & Perin, E. C. (2019) · Circulation Research · doi:10.1161/circresaha.119.314951 · Cited by 89
HIGH TUMOUR NECROSIS FACTOR-α LEVELS ARE ASSOCIATED WITH EXERCISE INTOLERANCE AND NEUROHORMONAL ACTIVATION IN CHRONIC HEART FAILURE PATIENTS
Cicoira, M., Bolger, A. P., Doehner, W., Rauchhaus, M., Davos, C. H., Sharma, R. K., Al-Nasser, F., Coats, A. J. S., & Anker, S. D. (2001) · Cytokine · doi:10.1006/cyto.2001.0918 · Cited by 85
Cardiovascular Biomarkers in CKD: Pathophysiology and Implications for Clinical Management of Cardiac Disease
Roberts, M. A., Hare, D. L., Ratnaike, S., & Ierino, F. L. (2006) · American Journal of Kidney Diseases · doi:10.1053/j.ajkd.2006.06.005 · Cited by 86
Red Cell Distribution Width and Other Red Blood Cell Parameters in Patients with Cancer: Association with Risk of Venous Thromboembolism and Mortality
Riedl, J., Posch, F., Königsbrügge, O., Lötsch, F., Reitter, E., Eigenbauer, E., Marosi, C., Schwarzinger, I., Zielinski, C. C., Pabinger, I., et al. (2014) · PLoS ONE · doi:10.1371/journal.pone.0111440 · Cited by 85
“It is known that inflammatory states and release of inflammatory cytokines, such as tumor necrosis factor (TNF)-alpha or interleukin-6, disrupt erythropoiesis [27,28].”
The interleukin-6/interleukin-6-receptorsystem is activated in donor hearts
Plenz, G. A. M., Eschert, H., Erren, M., Wichter, T., Böhm, M., Flesch, M., Scheld, H. H., & Deng, M. C.-H. K. (2002) · Journal of the American College of Cardiology · doi:10.1016/s0735-1097(02)01791-6 · Cited by 85
Safety of biologic therapy in rheumatoid arthritis
Woodrick, R. S., & Ruderman, E. (2011) · Nature Reviews Rheumatology · doi:10.1038/nrrheum.2011.145 · Cited by 85
“High levels of cytokines, including TNF, have been reported in patients with CHF since the 1990s”
Background
A wearable hemofilter for continuous ambulatory ultrafiltration
Gura, V., Ronco, C., Nalesso, F., Brendolan, A., Beizai, M., Ezon, C., Davenport, A., & Rambod, E. (2007) · Kidney International · doi:10.1038/sj.ki.5002711 · Cited by 85
Elevation of circulating fatty acid-binding protein 4 is independently associated with left ventricular diastolic dysfunction in a general population
Fuseya, T., Furuhashi, M., Yuda, S., Muranaka, A., Kawamukai, M., Mita, T., Ishimura, S., Watanabe, Y. S., Hoshina, K., Tanaka, M., et al. (2014) · Cardiovascular Diabetology · doi:10.1186/s12933-014-0126-7 · Cited by 85
“Up-regulation of FABP4 expression and other adipokines in heart failure has been demonstrated in recent studies [26-28], indicating complex neurohormonal and metabolic abnormalities associated with heart failure.”
Insulin inhibits tumor necrosis factor-α induction in myocardial ischemia/reperfusion: Role of Akt and endothelial nitric oxide synthase phosphorylation*
Li, J., Zhang, H., Wu, F. Y., Nan, Y., Ma, H., Guo, W., Wang, H., Ren, J. T., Das, U. N., & Gao, F. (2008) · Critical Care Medicine · doi:10.1097/ccm.0b013e3181782335 · Cited by 85
Prognostic Utility of ST2 in Patients with Acute Dyspnea and Preserved Left Ventricular Ejection Fraction
Shah, K. B., Kop, W. J., Christenson, R. H., Diercks, D. B., Henderson, S., Hanson, K., Li, S.-Y., & deFilippi, C. R. (2011) · Clinical Chemistry · doi:10.1373/clinchem.2010.159277 · Cited by 85
Leg flow-mediated arterial dilation in elderly patients with heart failure and normal left ventricular ejection fraction
Hundley, W. G., Bayram, E., Hamilton, C. A., Hamilton, E. A., Morgan, T. M., Darty, S. N., Stewart, K. P., Link, K. M., Herrington, D. M., & Kitzman, D. W. (2006) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00567.2006 · Cited by 84
“To understand why FMAD was preserved in HFNEF relative to HFREF participants, we performed analysis of covariance, adjusting for a wide range of variables known to influence peripheral arterial endothelial function, including patient demographics and co-morbidities (such as tobacco use, diabetes, or hypercholesterolem…”
Method
Association of Hyperadiponectinemia With Severity of Ventricular Dysfunction in Congestive Heart Failure
Nakamura, T., Funayama, H., Kubo, N., Yasu, T., Kawakami, M., Saito, M., Momomura, S.-I., & Ishikawa, S.-E. (2006) · Circulation Journal · doi:10.1253/circj.70.1557 · Cited by 84
Myocyte signalling in leucocyte recruitment to the heart
Ghigo, A., Franco, I., Morello, F., & Hirsch, E. (2014) · Cardiovascular Research · doi:10.1093/cvr/cvu030 · Cited by 83
Change in circulating cytokines after 2 forms of exercise training in chronic stable heart failure
LeMaitre, J. P., Harris, S., Fox, K. A. A., & Denvir, M. A. (2003) · American Heart Journal · doi:10.1016/j.ahj.2003.07.001 · Cited by 84
Cross-regulation between the renin?angiotensin system and inflammatory mediators in cardiac hypertrophy and failure
SEKIGUCHI, K. (2004) · Cardiovascular Research · doi:10.1016/j.cardiores.2004.02.005 · Cited by 84
“Relevant to this discussion is the recent observation that a second class of biologically active molecules, termed cytokines, has also been identified in the setting of heart failure [6,7].”
Background
Circulating Levels of Tumor Necrosis Factor Correlate With Indexes of Depressed Heart Rate Variabilitya
Malave, H. A., Taylor, A. A., Jaggarao, N. S. V., Deswal, A. M., & Mann, D. L. (2003) · CHEST Journal · doi:10.1378/chest.123.3.716 · Cited by 84
The Gut and Intestinal Bacteria in Chronic Heart Failure
Sandek, A., Anker, S. D., & von Haehling, S. (2009) · Current Drug Metabolism · doi:10.2174/138920009787048374 · Cited by 84
“The concentrations of circulating pro-inflammatory cytokines are known to be highest in patients with cardiac cachexia [3, 4850], and these patients have a particularly poor prognosis [51].”
Background
Effects of Pimobendan on Adverse Cardiac Events and Physical Activities in Patients With Mild to Moderate Chronic Heart Failure
The EPOCH Study Group (2002) · Circulation Journal · doi:10.1253/circj.66.149 · Cited by 84
Sites of interleukin-6 release in patients with acute coronary syndromes and in patients with congestive heart failure
Deliargyris, E., Raymond, R. J., Theoharides, T. C., Boucher, W. S., Tate, D. A., & DEHMER, G. J. (2000) · The American Journal of Cardiology · doi:10.1016/s0002-9149(00)01121-8 · Cited by 84
Endothelial function and proinflammatory cytokines in patients with ischemic heart disease and dilated cardiomyopathy
Tentolouris, C. A., Tousoulis, D., Antoniades, C. A., Bosinakou, E., Kotsopoulou, M., Trikas, A. G., TOUTOUZAS, P. K., & Stefanadis, C. (2004) · International Journal of Cardiology · doi:10.1016/j.ijcard.2003.08.002 · Cited by 84
Effect of Chronic Angiotensin-Converting Enzyme Inhibition on Endothelial Function in Patients with Chronic Heart Failure
Drexler, H. (1995) · The American Journal of Cardiology · doi:10.1016/s0002-9149(99)80497-4 · Cited by 84
Studies on Intragastric PCO2 at Rest and During Exercise as a Marker of Intestinal Perfusion in Patients with Chronic Heart Failure
Krack, A., Richartz, B. M., Gastmann, A., Greim, K., Lotze, U., Anker, S. D., & Figulla, H. R. (2004) · European Journal of Heart Failure · doi:10.1016/j.ejheart.2004.03.002 · Cited by 83
Mechanisms of cardiac dysfunction in diabetic cardiomyopathy: molecular abnormalities and phenotypical variants
Prandi, F. R., Evangelista, I., Sergi, D., Palazzuoli, A., & Romeo, F. (2022) · Heart Failure Reviews · doi:10.1007/s10741-021-10200-y · Cited by 86
“Lastly, a key contributing role in development and progression of myocardial injury and LV dysfunction is played by inflammatory cytokines such as IL-1β, IL-6, TNF-α, and TGF-β1 and the inflammatory transcriptional regulator NFκB, leading to dilated CMD [42, 43].”
Background
Overexpression of cardiac I-κBα prevents endotoxin-induced myocardial dysfunction
Haudek, S. B., Spencer, E., Bryant, D. D., White, D. J., Maass, D. L., Horton, J. W., Chen, Z. J., & Giroir, B. P. (2001) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.2001.280.3.h962 · Cited by 83
“TNF-a has been detected in several human cardiacrelated conditions, including congestive heart failure and septic cardiomyopathy (22, 25), and is thought to be one of a number of NF-kB-dependent genes involved in septic cardiomyopathy.”
Background
Intracarotid tumor necrosis factor-α administration increases the blood-brain barrier permeability in cerebral cortex of the newborn pig: quantitative aspects of double-labelling studies and confocal laser scanning analysis
Ábrahám, C. S., Deli, M. A., Joo, F., Megyeri, P., & Torpier, G. (1996) · Neuroscience Letters · doi:10.1016/0304-3940(96)12546-5 · Cited by 82
Left ventricular vs. biventricular mechanical support: Decision making and strategies for avoidance of right heart failure after left ventricular assist device implantation
Dandel, M., Krabatsch, T., & Falk, V. (2015) · International Journal of Cardiology · doi:10.1016/j.ijcard.2015.06.103 · Cited by 81
Exercise Training in Congestive Heart Failure: Risks and Benefits
Keteyian, S. J. (2011) · Progress in Cardiovascular Diseases · doi:10.1016/j.pcad.2011.02.005 · Cited by 80

Authors: Levine, B., Kalman, J., Mayer, L., Fillit, H. M., & Packer, M.
Affiliations: City University of New York (US)
ORCID: Levine, Beth
Fillit, Howard M.
Packer, Milton
Venue: New England Journal of Medicine
Publisher: Massachusetts Medical Society
Published: 1990-07-26
Volume: 323
Issue: 4
Pages: 236-241
ISSN: 0028-4793 (ISSN-L)
1533-4406
DOI: 10.1056/nejm199007263230405
OpenAlex: W2324476825
Cited by: 2,582
References: 55
Citations by year: 2026: 21 · 2025: 43 · 2024: 49 · 2023: 34 · 2022: 70 · 2021: 63 · 2020: 64 · 2019: 64 · 2018: 59 · 2017: 64 · 2016: 58 · 2015: 70 · 2014: 75 · 2013: 73 · 2012: 79
FWCI: 29.44
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: New England Journal of Medicine (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (7r01hl025055-11, 5r01ca041583-06, 5k04hl001229-02)
National Heart, Lung, and Blood Institute (KO4-HL-01229, R01-HL-25055)
National Cancer Institute (R01-CA41583)
Topics: Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Failure Treatment and Management
Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
Health Sciences › Medicine › Physiology (medical) › Nutrition and Health in Aging
Keywords: TNF-α, chronic heart failure, cardiac cachexia, serum cytokines, plasma renin activity, serum sodium, hemoglobin, blood urea nitrogen, chronic kidney disease, cytokine clearance, advanced heart failure, weight loss, inflammation in heart failure, anemia of heart failure, hyperuricemia, hyperkalemia
MeSH terms: Adult, Aged, Aged, 80 and over, Chronic Disease, Female, Heart Failure, Hemoglobins, Humans, Male, Middle Aged, Renin, Sodium, Tumor Necrosis Factor-alpha

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Elevated Circulating Levels of Tumor Necrosis Factor in Severe Chronic Heart Failure

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Self-check

Citations

Cites

Cited by

Related

Metadata

Record

About these checks