Effect of Thalidomide on Cardiac Remodeling in Chronic Heart Failure

Gullestad, Lars; Ueland, Thor; Fjeld, Jan Gunnar; Holt, Even; Gundersen, T; Breivik, Kyrre; Følling, Magne; Hodt, Anders; Skårdal, Rita; Kjekshus, John; Andreassen, Arne K.; Kjekshus, Elin; Wergeland, Ragnhild; Yndestad, Arne; Frøland, Stig S.; Semb, Anne Grete; Aukrust, Pål

doi:10.1161/circulationaha.105.564971

Cited by 78 publications

(44 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In our cases an important heart rate reduction was observed that has been proposed as a beneficial mechanism to reduce the ischemic role even in non-ischemic HF patients, improving contractile function by decreasing myocardial oxygen demand [32], as show our present results, with no difference regarding HF etiology.…”

Section: Discussionsupporting

confidence: 82%

“…In their cases, increased ejection fraction was observed in those patients who received the highest thalidomide doses [32], as well as an improvement in left ventricular diameters. In spite of these, as in our cases, in this new paper of Gullestad no TNF-α downregulation was observed as previously, suggesting that other mechanisms as significant reduction of neutrophil count and MMP-2 plasma levels are perhaps involved [32]. …”

Section: Discussionmentioning

confidence: 99%

“…On the other hand, effects of thalidomide could be related not only to its effect on cytokines but also on unknown effects of matrix degradation, as has been demonstrated by the downregulation of MMP-2 as a mediator of worsening of cardiac function through ventricular remodeling [32]. Finally, while several studies have focused on the possible pathogenic role of TNF-α and targeted therapy against this molecule, further research in this area will be necessary to identify the most important factors in the immunopathogenesis of CHF in order to develop more specific immunomodulating agents in this disorder.…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Effects of Thalidomide Treatment in Heart Failure Patients

Orea-Tejeda¹,

Arrieta

Castillo-Martı́nez³

et al. 2006

Cardiology

View full text Add to dashboard Cite

Background: Several studies have reported a direct association between elevated plasma levels of inflammatory cytokines and worse functional class (New York Heart Association [NYHA]) and cardiac function, measured as left ventricular ejection fraction (LVEF). Thalidomide has recently shown to improve LVEF in chronic heart failure patients, accompanied by a marked decrease in plasma levels of tumor necrosis factor alpha (TNF-α). Methods: In a randomized prospective open label study of men and women with heart failure (HF) due to ischemic and non-ischemic cardiomyopathy who had systolic dysfunction (LVEF <40%) and NHYA classification, functional classes II and III were assigned to control (without thalidomide, 60 patients) or thalidomide group (20 patients). The initial dose of thalidomide was 100 mg once a day, and it was increased to 100 mg twice a day after a period of 10 days, if the prior dosage was well-tolerated. Demographic characteristics, etiology of HF, prior myocardial infarction, co-morbidities associated were registered and laboratory routine test, TNF-α serum levels, and echocardiogram were obtained at the beginning and after 6 months of follow-up. Results: Clinical status (NYHA) at the end of the follow-up period, improved moderately in both groups. TNF-α levels were initially of 5.88 ± 0.9 and 6.49 ± 1.82 vs. 6.32 ± 1.6 and 7.94 ± 3.8 pg/ml during follow-up, for thalidomide and control groups, respectively. There were non-significant differences in echocardiography variables. Conclusion: In conclusion, although there is a large amount of information supporting a direct relationship between TNF-α and worsening of symptoms and prognosis in patients with HF and recently, the beneficial effect on thalidomide treatment has been suggested, these preliminary observations should be confirmed in a larger prospective study, specially trying to clarify the action mechanisms.

show abstract

Section: Discussionsupporting

confidence: 82%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Effects of Thalidomide Treatment in Heart Failure Patients

Orea-Tejeda¹,

Arrieta

Castillo-Martı́nez³

et al. 2006

Cardiology

View full text Add to dashboard Cite

show abstract

“…173 Secondary to its anti-inflammatory and immunomodulating effects, thalidomide has been studied as a potential HF therapeutic agent with beneficial effects on LVEF and matrix metalloproteinase production. 174 Lenalidomide has been associated with hypersensitivity myocarditis in case reports. 175 Similarly, high-dose interleukin-2 has been associated with fulminant myocarditis, which is poorly understood but may be related to the capillary leak syndrome and cytotoxic damage from migration of lymphocytes and inflammatory cells to the interstitum.…”

Section: Taxanesmentioning

confidence: 99%

Drugs That May Cause or Exacerbate Heart Failure

Page¹,

O’Bryant²,

Cheng³

et al. 2016

Circulation

357

185

View full text Add to dashboard Cite

Heart failure is a common, costly, and debilitating syndrome that is associated with a highly complex drug regimen, a large number of comorbidities, and a large and often disparate number of healthcare providers. All of these factors conspire to increase the risk of heart failure exacerbation by direct myocardial toxicity, drug-drug interactions, or both. This scientific statement is designed to serve as a comprehensive and accessible source of drugs that may cause or exacerbate heart failure to assist healthcare providers in improving the quality of care for these patients.

show abstract

“…Notable are also MMP-9-lowering effect of statins [113][114][115][116] and matrix effects of thiazolidinediones [117,118], angiotensin-converting enzyme inhibitors [119][120][121][122][123][124], angiotensin II-receptor antagonists [125,126], and spironolactone [106,124]. In a small study of heart failure patients, thalidomide treatment lowered MMP-2 and also improved LV systolic function [127].…”

Section: Extracellular Matrix Peptidesmentioning

confidence: 99%

Myocardial Biomarkers for Prediction of Cardiovascular Disease

Sundström

2009

Disease Markers

View full text Add to dashboard Cite

Abstract. The identification of those persons in the population who have the highest risk of future cardiovascular events is important for targeting intensive preventive efforts. This can be reliably done using a handful of long since established risk factors. The unmet need for new molecular biomarkers for prediction of cardiovascular events in the general population is therefore low. In order for a new biomarker to be used clinically for risk prediction, a statistically significant association of levels of the biomarker to adverse outcome is not enough, but the biomarker should also be demonstrated to add discriminative capacity beyond established risk factors. In contrast to the limited value of new biomarkers for risk prediction, their usefulness for unraveling the pathophysiology of cardiovascular disease is large. The myocardium is the source of a vast number of interesting biomarkers, of which a few may be useful for risk prediction in the general population. Two of these, troponin-I and the N-terminal fragment of brain natriuretic peptide, have passed tests of added discriminatory value. Numerous other biomarkers produced by cardiomyocytes or non-cardiomyocytes in the myocardium are promising, and if they are not proven useful for risk prediction, they will unquestionably enhance our understanding of cardiovascular disease.Keywords: Risk, epidemiology, population, biomarker, peptide, myocardium The need for prediction and prevention of cardiovascular eventsCardiovascular diseases kill half of the population in developed countries, and seriously disable a further large number. A high cardiovascular disease death rate in elderly persons is unavoidable, but prevention of cardiovascular deaths in younger individuals is highly prioritized, as recently outlined in the European Heart Health Charter [1].Sudden cardiac death is sometimes the first manifestation of cardiovascular disease, and traditional risk factors can be identified beforehand in a minority of these persons [2]. Further, one out of four myocardial infarctions resulting in Q-waves are asymptomatic [3], and smaller myocardial infarctions may be asymptomatic * Corresponding author: Johan Sundström, MD PhD, Department of Medical Sciences, Uppsala University Hospital, SE-751 85 Uppsala, Sweden. Tel.: +46 18 6119889 or +46 70 4225220; Fax: +46 18 509297; E-mail: johan.sundstrom@medsci.uu.se. in as much as four out of five victims [4]. Hence, the high risk strategy will not be sufficient in these cases.In order to prevent as many of premature cardiovascular deaths as possible, the Charter therefore calls for the use of both the population strategy (treating the whole population with measures such as smoking prevention or cessation, physical activity, and fruit and vegetable intake) and the high-risk strategy (identifying persons at high risk and treating risk factors aggressively). This article reviews some of the tools available for the latter strategy. The role of biomarkers in the identification of high-risk personsThe term risk factor was coined fi...

show abstract

Effect of Thalidomide on Cardiac Remodeling in Chronic Heart Failure

Cited by 78 publications

References 37 publications

Effects of Thalidomide Treatment in Heart Failure Patients

Effects of Thalidomide Treatment in Heart Failure Patients

Drugs That May Cause or Exacerbate Heart Failure

Myocardial Biomarkers for Prediction of Cardiovascular Disease

Contact Info

Product

Resources

About