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[ 92 ]. Nineteen out of 38 patients (50%) who developed new-onset heart failure had
no identifiable risk factor for heart failure [ 92 ]. One patient died [ 92 ].
The clinical symptoms reported in patients with anti-TNF associated heart fail-
ure are similar to those seen in classic heart failure. Patients may present with
fatigue, dyspnea, paroxysmal nocturnal dyspnea, lower extremity edema, and/or
chest pain [ 92 ]. On diagnostic evaluation, decreased left ventricular function on
echocardiogram, increased pulmonary pressure on cardiac catheterization, and/or
pulmonary congestion on chest radiography are hallmark findings [ 92 ].
Risk Factors
The anti-TNF agents most documented to be associated with new onset or exacerba-
tion of heart failure are etanercept and infliximab [ 92 ]. However, in 2013, Adamson
et al. reported a case of fulminant heart failure in a 51-year-old woman after receipt
of the second dose of adalimumab for treatment of polychondritis [ 101 ]. The dura-
tion of treatment does not appear to be a predisposing risk factor for new onset or
exacerbation of heart failure. In the case series described by Kwon et al., new-onset
heart failure and exacerbation of heart failure can occur as early as 24 h after admin-
istration of anti-TNF therapy or as late as 2 years after initiating treatment [ 92 ].
The effect that anti-TNF therapy has on exacerbation of heart failure may be
dose-dependent. In a prospective trial, 150 patients with NYHA class III and IV
heart failure were randomized to receive placebo, infliximab 5 mg/kg or infliximab
10 mg/kg. Patients randomized to 10 mg/kg infliximab had an increased risk of
hospitalization for heart failure and increased risk of death through 28 weeks fol-
low- up [ 98 ]. A correlation between heart failure and dose of anti-TNF therapy has
not been confirmed in other reports.
Lastly, it appears that the traditional risk factors of heart failure may not be
present in patients with anti-TNF therapy-associated heart failure. In the case
series published by Kwon et al., new-onset heart failure after anti-TNF therapy
was reported in the same number of patients with documented risk factors
including cardiovascular disease and diabetes as those without traditional risk
factors (19) [ 92 ].
Pathophysiology
The pathophysiology of anti-TNF therapy-associated heart failure has not been well
delineated. Chronic heart failure is believed to be influenced by over-activation of
the sympathetic nervous and neurohormonal systems [ 92 ]. A deteriorating heart
with hemodynamic overload or myocardial stretch stimulates the immune system
and TNF-α production [ 102 ]. Unlike in RA and IBD, heart failure is not purely an
inflammatory condition. Low TNF-α level confers a cytoprotective effect in the
U. Wong and R.K. Cross