Design of therapy for advanced heart failure.

Advanced heart failure has been defined as persistent symptoms (NYHA class III-IV) that limit daily life despite routine therapy with agents of known benefit. Although these symptoms can occur both with low and preserved ejection fraction, the majority of reported experience is with low ejection fraction, usually <25%. For this population with expected one year mortality of 30-50%, over twice the mortality of the landmark trials of medical therapy, there is little trial data to guide management, which is based largely on collected experience. Once the disease has progressed to this stage, therapy focuses upon the twin goals of symptom relief and prolongation of survival and is guided according to the hemodynamic profiles defined by clinical assessment. As symptoms at this stage relate largely to the congestion, therapy is targeted to reduction of elevated pulmonary venous and/or systemic venous pressures to near normal levels. The most common obstacle to relief of congestion is the increasingly recognized cardio-renal syndrome, for which both understanding and therapy are currently limited. Design of the outpatient regimen for advanced heart failure must be tailored to the individual patient. Many patients with advanced heart failure cannot tolerate "target" doses of neurohormonal antagonists, and spironolactone should be used only when clinical and renal function are sufficiently stable and frequently monitored in order to avoid life-threatening hyperkalemia. The clinical benefit of bi-ventricular pacing is substantial for the small proportion of patients likely to benefit. The vast majority of patients will never be eligible for cardiac transplantation or ventricular assist devices. To derive maximal benefit from all available therapies, heart failure disease management with collaboration of physicians and specialized nurses offers the greatest benefit to the greatest number of patients with advanced heart failure.