Think Small and Examine the Constituents of Left Ventricular Hypertrophy and Heart Failure: Cardiomyocytes Versus Fibroblasts, Collagen, and Capillaries in the Interstitium

L eft ventricular hypertrophy (LVH) and heart failure areprevalent and frequently encountered conditions, but several fundamental issues about LVH and heart failure remain unresolved. Although it is well known that hyperten-sion can lead to LVH, which then heralds adverse events such as heart failure, arrhythmia, myocardial infarction, and mortality, the mechanisms mediating these events remain unclear. Weber and Brilla articulated this long-standing dilemma>20 years ago: “An explanation for why a presump-tive adaptation such as LVH would prove pathological has been elusive.”1 They too cited even earlier investigators such as Wearn, who wrote in 1940, “The frequent finding at necropsy of a hypertrophied heart that has failed is familiar to all. Other than the hypertrophy, the muscle of these hearts often shows no abnormalities. Why, then, should an enlarged muscle without demonstrable abnormality fail? Hypertrophy is frequently spoken of as being compensatory. On the other hand, it is also considered to be one of the most dependable signs of heart damage.”2 In this issue of the Journal of the American Heart Association, Tsao et al meticulously analyze carefully col-