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Exercise testing using gas exchange analysis, or cardiopulmonary exercise testing (CPET), is a remarkably useful and versatile tool. CPET has evolved over time and, currently, constitutes a unique clinical approach for study of a variety of cardiopulmonary disorders that may be associated with symptoms or limit exercise performance.1–3 Use of CPET has become more common recently, with increasing recognition that assessment of cardiac and pulmonary function at rest cannot reliably predict functional capacity, and that disease stages and severity correlate better with exercise parameters than with resting measurements. Indeed, CPET provides an overall assessment of the integrated, multiorgan response to exercise involving the oxygen-uptake cascade, including the lung, cardiovascular system, skeletal muscle, and cellular pathways for oxygen utilization.

The precision of the technology used in CPET is remarkable, and the technique provides information that facilitates an understanding of the pathophysiology underlying exercise impairment. Additionally, it enables insight into how therapeutic interventions impact effort limitation, and identifies useful markers of prognosis.4

A thorough evaluation of gas exchange parameters in response to various cardiopulmonary disorders was proposed in the early 1980s, including pioneering studies by Weber and Janicki.5,6 Recently, use of CPET has been expanded considerably. Combination modalities, for example, CPET coupled with echocardiography (CPET imaging),7 and invasive assessment of systemic and pulmonary hemodynamics have been described.

This chapter provides a conceptually balanced discussion of CPET applications based on expert recommendations, guidelines, and available data.


When physically challenged, for example, during exercise, the body behaves as a “machine in harmony,” integrating and promoting the interaction of multiple organs and pathways. O2 delivery from ambient air to mitochondria is essential to aerobic performance. Optimal O2 delivery depends on a set of elegant biologic interactions among the functional components of the O2 transport chain, including oxygenation of blood in the lung (via gas diffusion in the alveoli); O2 transport in blood, in both hemoglobin-bound and dissolved forms; redistribution of blood flow to working muscles; adequate O2 release and tissue O2 extraction in metabolizing tissues; and diffusion of O2 from capillaries into metabolizing cells (Fig. 32-1).

Figure 32-1

Organ systems involved in the O2 utilization chain.

Direct measurement of oxygen uptake (V̇O2), typically expressed as V̇O2max (in healthy subjects) or as peak V̇O2 (in patients), and normalized for body weight (mL/kg/min), defines maximal exercise performance and related limits of the cardiopulmonary system.5

One’s ability to perform physical activity is critically related to the cardiopulmonary system’s capacity to supply O2 and clear carbon dioxide (CO2) from exercising muscle. During this process, delivery of O2 to mitochondria is essential to performing ...

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