Progress in the development of a unifying hypothesis on the mechanisms underlying the electrical and mechanical abnormalities of the failing heart: one step backward but two steps forward.

The incidence and prevalence of death and disability from heart failure have steadily increased over the last two decades despite the overall decline in the age-adjusted death rates for cardiovascular diseases in general during the same period [1,2]. As of 2003, the incidence of heart failure is estimated at 550,000 new cases per year and the prevalence of heart failure is approximately 5 million patients or 2.3% of the total population [2]. Alarmingly, the prevalence of some degree of cardiac dysfunction may be considerably higher with a 2003 study of a representative Minnesota population showing a prevalence of systolic dysfunction of 6% and diastolic dysfunction of 28.1% [1]. Based on Framingham Heart Study data, the lifetime risk of developing heart failure in men and women is staggering at 1 in 5 individuals [3]. Of those individuals under the age of 65, 80% of men and 70% of women will die within 8 years and the 1-year mortality is extraordinarily high at 1 in 5 [2]. Consequently, overall deaths from heart failure have increased 20.5% from 1993–2003. The two major causes of death in heart failure patients are mechanical pump failure and electrical abnormalities leading to cardiac arrhythmias with the incidence of sudden cardiac death being 6–9 times greater in heart failure patients compared with the general population. In light of these alarming statistics, it is not surprising that the number of heart failure-related hospital discharges increased by 174% from 1979 to 2003; and that the estimated direct and indirect cost of heart failure in this country for 2006 is $29.6 billion [2]. Clearly, our current preventive and therapeutic heart failure strategies have failed to reverse this epidemic proportion of heart failure and to lessen the human and economic costs of heart failure on our society. After decades of intensive clinical and basic science investigations, the precise mechanisms that are responsible for both the contractile and electrical abnormalities characteristic of heart failure remain unclear. Progress has been hindered, in part, by the fact that the mechanical and electrical phenotype of the failing heart represents the “triangulation” of a host of physiological, neurohumoral, and biochemical abnormalities that are the consequence of the interplay of multiple and complex genetic and environmental influences.