Alteration of excitation-contraction coupling in the failing human heart was deemed an interesting subject for a dialogue between basic scientists and clinical researchers in continuation of previous Gargellen Conferences concerned with the function of the normal and failing human myocardium. In 1987 basic mechanisms and clinical implications of then new insights into cardiac energetics was followed by a comprehensive review of inotropic stimulation and myocardial energetics in 1989. Here, we undertook a re-evaluation of the principles of inotropic stimulation and of its potential therapeutic value, based on new observa tions from experiments with human myocardium. In 1992 the risk due to myocardial phenotype change as a consequence of adaptation in heart failure was published. Here, alterations of subcellular structures and functions as a consequence of chronic heart failure, summarized as phenotype change, could be described as an essential characteristic of the failing human myocardium. This topic was discussed in greater depth in the volume "Cellular and Molecular Alterations in the Failing Human Heart," considering both the sarcolemma and the phosphodiesterases, as well as excitation-contraction coupling and contractile proteins, extracellular matrix, and mitrochondrial function."

The myocardium in heart failure: Cellular and subcellular alterations in the failing human myocardium. H. Just Medizinische Universitatsklinik Freiburg i. Br., Innere Medizin III - Kardiologie, FRG The syndrome of heart failure continues to be a major challenge to clinicians and scientists. Incidence and mortality of the disease are high, the patient is disabled, and is permanently threatened by the high morbidity and mortality. The clinician faces a syndrome of complex pathophysiology. Multiple causes or underlying disorders of the heart have to be differentiated from heart failure itself, which often results in exceedingly difficult diagnoses. Likewise, prognostication meets with difficulties due to problems in separating influences of the underlying disease and the heart failure syndrome itself. In chronic refractory failure annual mortality may exceed 50%. If aortic stenosis or ischemic cardiomyopathy with main stem lesions are present, this percentage may be even higher. The situation becomes particularly threatening to the patient when the reduction in cardiac performance goes along with complex ventricular arrhythmias. Therapy has remained difficult and of limited effectiveness. Major progress was achieved with the introduction of diuretic substances. Of similar importance was the introduction of va so dilating drugs into the treatment of heart failure. The principle of vasodilation has greatly improved our understanding of the disease, and has brought about a major improvement of symptoms, increase of exercise capacity, and reduc tion of mortality. This is especially true for the introduction of the angiotensin converting enzyme inhibitors.