Immunosuppressive therapy for heart failure: a guide to patient selection

Therapy with beta-adrenoceptor antagonists, ACE inhibitors and most recently, spironolactone was established for reducing all-cause mortality in patients with congestive heart failure (CHF), improving patient clinical status and inhibiting the disease progression. Unfortunately, despite optimal therapy for CHF in some patients, the disease progresses and, as yet, no conclusive mechanism has been identified for deterioration of cardiac function in patients with heart failure. Defining the cause of CHF in patients with dilated cardiomyopathy may have prognostic and therapeutic implications. Clinical and experimental evidence suggests that long-term inflammation may play a key part in the development of heart failure in patients with cardiomyopathy due to ischemic heart disease and those with cardiomyopathy due to non-ischemic cases. Because chronic immune myocardial injury, found in patients with CHF is myocardial restricted, endomyocardial biopsy with immunohistological markers of immune-mediated injury may offer us new guidelines to patient selection for immunomodulatory therapies. Few randomized placebo controlled studies addressing the effectiveness of suppression and modulation of the immune system in patients with heart failure gave unequivocal results. Moreover, none of the abovementioned randomized studies has shown decreased mortality in the immunosuppressively treated patients compared with conventionally treated patients. In the US Myocarditis Treatment Trial, for example, mortality was 20% overall at 1 year and 56% at 4.3 years of follow-up. In addition, spontaneous improvement of left ventricular systolic function has been reported in 30-40% of conventionally treated patients with CHF due to dilated cardiomyopathy. Given the high proportion of patients who improve spontaneously, selection of patients for immunosuppressive therapy should be preceded by treating heart failure with the individualized conventional therapy (ACE inhibitors, beta-adrenoceptor antagonists, spironolactone) for at least 6 months. Final decision to use immunomodulatory therapies should be based on comprehensive clinical measures of disease progression.