Defining success in heart failure: the end-point mess.

I n 1986, the landmark vasodilator trial, the Vasodilator– Heart Failure Trial (V-HeFT-1), ushered in a modern therapeutic regimen that provided hope, for the first time, to millions of patients suffering from and dying of heart failure. 1 Entry criteria for the trial were simple and confined to men with " impaired cardiac function and reduced exercise tolerance. " The primary end point was all-cause mortality. Most clinicians did not quibble about the borderline statistical significance of the overall study, recognizing that a new era of heart failure therapy and clinical trials had begun. The Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS) 2 and Studies of Left Ventricular Dysfunction (SOLVD) 3 were published subsequently, in 1987 and 1991, respectively, further refining patient selection while molding a new generation of cardiologists, many of whom became heart failure specialists. Since those heady times, the evolution of therapy for heart failure has become increasingly complex. The managing clinician must integrate a number of factors about the individual heart failure patient before adding treatments to the pharmacological foundation of renin-angiotensin and ␤-adrenergic inhibition. Crucial historical or phenotypic variables may include left ventricular ejection fraction (LVEF), functional classification and/or exercise tolerance, history and timing of previous arrhythmias or myocardial infarction, QRS duration and current rhythm, duration of heart failure symptoms , adequacy of or intolerance to optimization of medical therapy, gender, race, cause of the cardiomyopathy, valvular competence, and renal function. Important patient characteristics currently determine eligibility for additional medications , electric devices, surgical procedures, cardiac transplan-tation, ventricular assist devices, endomyocardial biopsy, cardiac rehabilitation, hospitalization, or hospice. This process of exacting classification of disease has served other disciplines well; imagine outcome trials for the wide range of thrombolytic or antiplatelet agents without the concomitant and careful descriptors of the manifestations of the acute coronary syndrome. 4 Likewise, the oncology community uses an increasingly precise language to further improve their staged battle again malignancy. Witness the narrative received from an oncological consultant about a patient categorized on the cardiac chart as having amyloid with moderate heart failure: " This 59 year-old man with primary (AL) amyloidosis, demonstrated by amyloid deposition on cardiac biopsy (with IHC stains consistent with lambda light chain deposition), elevated serum free lambda light chains, and faint lambda light chains visible on SPEP. It is manifested as class II heart failure, with possible tongue enlargement but no evidence of peripheral nerve, liver, gastrointestinal, …