Current Vascular Pharmacology, 2009, 7, 557-569 557 1570-1611/09 $55.00+.00 © 2009 Bentham Science Publishers Ltd. The Impact of Pharmacotherapy on the Cardiopulmonary Exercise Test Response in Patients with Heart Failure: A Mini Review Marco Guazzi 1 and Ross Arena 2,* 1 Cardiopulmonary Laboratory, Cardiology Division, University of Milano, San Paolo Hospital, Milano, Italy; 2 Departments of Internal Medicine, Physiology and Physical Therapy, Virginia Commonwealth University, Richmond, VA, USA Abstract: Cardiopulmonary exercise testing (CPX) is a well-recognized assessment technique in patients with HF. Venti- latory efficiency, aerobic capacity and heart rate recovery are several parameters obtained from CPX that accurately re- flect physiologic function and provide robust prognostic information. Pharmacotherapy is a vital component to the man- agement of patients with HF. Numerous pharmacologic interventions, such as ACE inhibition and beta-blockade have demonstrated significant physiologic and prognostic improvement in this population. Furthermore, a number of investiga- tions demonstrating a positive change in the CPX response resulting from a pharmacologic intervention now exist. Be- cause CPX variables reflect pathophysiologic processes differently, their response to a given pharmacologic is unique. For example, beta-blockade has been shown to significantly improve ventilatory efficiency, one of the most powerful prog- nostic markers obtained from CPX, while not altering aerobic capacity or heart rate recovery. Conversely, ACE and phos- phodiesterase-5 inhibition appears to improve ventilatory efficiency and aerobic capacity. Given the prognostic value of CPX, gauging its improvement from pharmacotherapy may be advantageous in facilitating optimal titration of medica- tions. A comprehensive review describing the physiologic and prognostic importance of CPX in the context of pharma- cotherapy does not exist. This mini review will: 1. Identify key CPX variables obtained from CPX including aerobic ca- pacity, ventilatory efficiency and heart rate recovery, 2. Describe the physiologic and prognostic significance of CPX in the heart failure population, and, 3. Summarize the present body of evidence addressing the change in CPX in response to different pharmacologic interventions including beta-blockade, renin-angiotensin-aldosterone axis inhibition and silde- nafil. Keywords: Ventilatory expired gas, ventilatory efficiency, aerobic capacity, pharmacologic. INTRODUCTION The management of patients with systolic heart failure (HF) continues to evolve in hopes of further improving qual- ity of life and functional capacity while reducing morbidity and mortality. Pharmacotherapy continues to play a central role in the treatment of this patient population, a trend that will certainly continue for the foreseeable future. Based upon a large body of scientific evidence, current HF practice guidelines recommend the use of beta-blockers and inhibi- tors of the renin-angiotensin-aldosternone axis in these pa- tients [1, 2]. Other pharmacologic agents, such as phos- phodiesterase-5 inhibitors [3], may also emerge as standards of care as this area continues to move forward. There are several clinically acceptable agents within each drug class used to treat the patient with HF, all with a varying range in acceptable dosages. The physiologic mechanism(s) of action of these pharmacologic agents on the cellular/single system level (i.e. vascular, central cardiac function, pulmonary func- tion) has been extensively investigated. Given the numerous pharmacologic options in combination with a heterogeneous physiologic response from 1 patient to the next, gauging the *Address correspondence to this author at the Departments of Internal Medicine, Physiology and Physical Therapy, Box 980224, Virginia Com- monwealth University, Health Sciences Campus, Richmond, VA 23298- 0224, USA; Tel: 804-828-0234; Fax: 804-828-8111; E-mail: raarena@.vcu.edu physiologic response to therapy from clinical perspective likewise becomes an important issue. From this clinical perspective, assessing the impact of a given intervention on the aerobic exercise performance of a patient with HF is afforded a high level of importance [1]. Cardiopulmonary exercise testing (CPX) is a highly reliable [4] and well accepted assessment technique for this purpose in the HF population. The American College of Cardiol- ogy/American Heart Association guidelines for exercise test- ing afford CPX a Class I rating (Conditions for which there is evidence and/or general agreement that a given procedure or treatment is useful and effective) for the “evaluation of exercise capacity and response to therapy in patients with heart failure who are being considered for heart transplanta- tion” [5]. This excerpt implies the use of CPX to assess the response to pharmacotherapy is warranted in patients with HF. While supported by a well-accepted clinical guideline, the use of serial CPX to assess the effectiveness of titration in pharmacotherapy is infrequent in practice. In present-day clinical practice, CPX is primarily used as a one-time evalua- tion for prognostic purposes, which is also well supported by the body of scientific evidence examining this topic [6]. From a research perspective, a number of investigations ex- amining the affect of various pharmacologic agents in HF have included CPX as either a primary or secondary end- point. Several pharmacologic agents, presently considered a