The advent of microprocessed “metabolic carts” and rapidly incremental protocols greatly expanded the clinical applications of cardiopulmonary exercise testing (CPET). The response normalcy to CPET is more commonly appreciated at discrete time points, for example, at the estimated lactate threshold and at peak exercise. Analysis of the response profiles of cardiopulmonary responses at submaximal exercise and recovery, however, might show abnormal physiologic functioning which would not be otherwise unraveled. Although this approach has long been advocated as a key element of the investigational strategy, it remains largely neglected in practice. The purpose of this paper, therefore, is to highlight the usefulness of selected submaximal metabolic, ventilatory, and cardiovascular variables in different clinical scenarios and patient populations. Special care is taken to physiologically justify their use to answer pertinent clinical questions and to the technical aspects that should be observed to improve responses’ reproducibility and reliability. The most recent evidence in favor of (and against) these variables for diagnosis, impairment evaluation, and prognosis in systemic diseases is also critically discussed. 1. Introduction Cardiopulmonary exercise testing (CPET) provides a means of unraveling abnormal physiologic functioning which may not be apparent at rest [1, 2]. The advent of microprocessed CPET systems [3] increased our technical capabilities in recording several variables throughout a single exercise bout—even of a relatively “short” duration of 10 minutes [4, 5]. The response normalcy to rapidly incremental CPET is more commonly judged by comparing the observed values at discrete time points (e.g., at the estimated lactate threshold (LT) and at peak exercise) with those previously obtained in apparently healthy subjects [6, 7]. It should be noted, however, that relying only in such discrete analysis leads to substantial loss of physiologic information given by the observation of the responses profiles during submaximal exercise and recovery [8–11]. In this context, authoritative textbooks [2, 12] and guidelines [13, 14] advocated that the trending of certain variables is a crucial component of the interpretative strategy as they might show substantial abnormalities even when the discrete values are still within the expected range [15–17]. Moreover, the response dynamics are highly reproducible [8–11], encompassing a range of exercise intensities which are likely to be faced by the patients in daily life [18–26]. Although the scientific
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