The Clinical Relevance of Circulating Tumor Necrosis Factor-a in Acute Decompensated Chronic Heart Failure Without Cachexia (Introduction)

In: Heart Failure

10 Dec 2013

The Clinical Relevance of Circulating Tumor Necrosis Factor-a in Acute Decompensated Chronic Heart Failure Without Cachexia (Introduction)Study objective: To evaluate the clinical relevance of circulating tumor necrosis factor-a (TNFa) in subjects with advanced acutely decompensated congestive heart failure (CHF) and to determine the modulatory effect of clinical interventions on short-term elaboration of this cytokine.
Design: Prospective, case-controlled study.
Setting: Inpatient and outpatient (hospital and clinic), at regional academic medical center. Patient interventions: Plasma concentrations of TNFa were determined in 25 healthy, normal control subjects and in 29 noncachectic patients with advanced CHF (mean ejection fractions 16 ±6%) who required hospitalization for IV diuretic and/or inotropic therapy despite optimization of oral medical regimens.

CHF patients were divided into two groups: diuretic responsive (group A; n=6) and diuretic resistant requiring inotropic support (group B; n=23). Group B was randomly allocated to receive either IV dobutamine (n=13) or milrinone (n=IO) for 72 h. TNFa levels in CHF patients were measured serially at baseline, at 6 h, at 48 h, at 72 h, and at I-week follow-up after hospital discharge.

Results: Plasma TNFa levels at baseline in CHF patients were 4.0 ±1.1 pg/mL (range, 0.5 to 6.5 pg/ mL) and 2.5 ±0.6 pg/mL (range, 0.5 to 6.8 pg/mL) in groups A and B, respectively, which were significantly different (p<0.002) from normal subjects (0.89±0.40 pg/mL; range, 0.5 to 9.7 pg/mL). Despite clinically successful therapy with IV diuretics, dobutamine, or milrinone, plasma levels of this cytokine remained unchanged. Plasma TNFa in CHF patients measured in recovery (1 week after hospital discharge) was 5.1 ±1.2 pg/mL (range, 1.0 to 9.9 pg/mL) and 3.9±0.8 pg/mL (range, 0.5 to 8.7 pg/mL) in groups A and B, respectively.

Conclusion: These findings suggest that although noncachectic patients with chronic heart failure who suffer acute decompensation elaborate significantly higher circulating levels of TNFa compared with healthy control subjects, no significant reduction or alteration in circulating TNFa is noted in the short-term follow-up despite clinical improvement.

Tumor necrosis factor-a (TNFa), a pleiotropic cytokine, produces multiple systemic effects, including anemia, cachexia, anorexia, and fever. More recently, several studies have demonstrated that this proinflammatory cytokine may play a compelling role in producing left ventricular dysfunction, dilated cardiomyopathy, hypotension, and pulmonary edema, all of which can accompany advanced heart failure. Indeed, in separate reports by Levine et al’ and Mc-Murray et al, increased levels of circulating TNFa were found in patients with stable but advanced congestive heart failure (CHF) associated with cachexia. To our knowledge, however, the clinical relevance of circulating TNFa in the unstable state of acute, decompensated, advanced CHF has not been investigated previously.

Furthermore, clinically used inotropic agents, including amrinone, a phosphodiesterase inhibitor, and vesnarinone, a quinolinone derivative, have been shown to suppress synthesis of TNFa in vitro. These important observations regarding the ability of conventional therapeutic agents to inhibit the synthesis of this cytokine suggest that these agents may exert additional salutary effects independent of their hemodynamic actions in advanced heart failure.

The purpose of this investigation was twofold. First, we sought to evaluate whether patients with chronic heart failure who suffer acute decompensation elucidate higher levels of circulating TNFa than healthy control subjects. Second, we examined whether clinical resolution from decompensated heart failure was associated with an improvement in circulating TNFa profiles.


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