Molecular Pathology of Dilated Cardiomyopathies

The term idiopathic, defined as being of unknown etiology or mechanism, is no longer applicable to the dilated cardiomyopathies. The tools of molecular biology and clinical investigation have made significant progress, and it is now to the rare and exceptional case that one is forced to apply the term idiopathic. Further, having arrived at more precise cause, direct therapeutic intervention will become possible. The concept of gene insertion and "genetic therapy" is under active investigation. Unfortunately, the significant advances in the cause and disease mechanisms of DCM have not been matched in therapeutics. With few exceptions, we indirectly treat the DCMs by managing the CHF syndrome. However, several important points have emerged. The concept of LV afterload reduction is valid and efficacious. The use of vasodilator therapy has significantly reduced both mortality and morbidity and, in certain forms of cardiomyopathy (e.g., hypertensive, alcoholic, and doxorubicin-related), have significantly altered hemodynamics and permitted the injured heart to heal and return to a near normal functional state. However, as much as we want to congratulate ourselves on the progress bought with the use of vasodilators and ACE inhibitors, one must keep in mind that under the best of circumstances, the DCMs still carry an unacceptably high morbidity and mortality. A 40% to 50% 4- to 5-year mortality rate is depressing. Herein lies the challenge. With the significant progress in pathogenesis and etiology, we now stand at the threshold of new, innovative advances in therapeutics. These new concepts in both therapeutics and prevention will require courage, dedication, and hard work. But bit by bit, these seemingly insolvable problems will yield to the discipline and imagination of the investigator. The DCMs will continue to be a challenging problem for future investigators. Progress has been dramatic, and it should continue even at an accelerated pace as we approach the twenty-first century.