FFR, from myocardial strips to the echo lab. Time sequence during stress echo (upper panel). The force-frequency relation is built off line. The force-frequency relationship is defined up-sloping when the peak exercise SP/ESV index is higher than baseline and intermediate stress values; biphasic, with an initial up-sloping followed by a later down-sloping trend, when the peak exercise systolic pressure/end-systolic volume index is lower than intermediate stress values; flat or negative, when the peak exercise systolic pressure/end-systolic volume index is equal to or lower than baseline stress values. The critical heart rate (or optimum stimulation frequency) is defined as the heart rate at which systolic pressure/end-systolic volume index reaches the maximum value during progressive increase in heart rate; in biphasic pattern, the critical heart rate is the heart rate beyond which the systolic pressure/end-systolic volume index has declined by 5%; in negative pattern the critical heart rate is the starting heart rate. The critical heart rate (or optimum stimulation frequency) is the human counterpart of the treppe phenomenon in isolated myocardial strips; the optimal heart rate is not only the rate that would give maximal mechanical performance of an isolated muscle twitch, but also is determined by the need for diastolic filling. Lower panel. Plots of average steady-state isometric twitch tension versus stimulation frequency in non-failing and failing myocardium. Measurements of twitch tension in isolated left-ventricular strips from explanted cardiomyopathic hearts compared with non-failing hearts show reduction in peak rates of generation and relaxation of twitch tension and a decrease in slope of tension rate vs. contraction frequency. The FFR of these failing groups both exhibit a negative treppe at contraction frequencies above about 100 bpm. The contraction frequency at which the FFR begins its descending limb ("optimum stimulation frequency") declines progressively in the order: ASD (atrial septal defect), CAD (coronary artery disease), IDDM (diabetic myopathy), MR (mitral regurgitation), and DCM (dilated cardiomyopathy). (Modified from: Mulieri AL. In "Heart Metabolism in Failure" R.A. Howarth Ed. 1997. The role of myocardial force-frequency relation in left ventricular function and progression of human heart failure).