Cardiopulmonary Exercise Testing Applications in HF
Cardiopulmonary Exercise Testing Applications in HF
American Heart Association/American College of Cardiology class recommendations and associated level of evidence for cardiopulmonary exercise testing (CPX) have been put forth. A new paradigm is proposed for CPX use and interpretation in heart failure (HF). Evidence for this new paradigm will be provided, showing that clinical utilization, class recommendations, and the associated level of evidence for CPX in the HF population can be expanded significantly.
The American Heart Association (AHA) and the American College of Cardiology (ACC) use a rigorous system for determining class recommendation and associated level of evidence for practice patterns, serving as the basis for their clinical guidelines. A detailed description of this system is provided elsewhere. The AHA/ACC has used this class recommendation/level of evidence system for the use of cardiopulmonary exercise testing (CPX) in patients with heart failure (HF). Initial guidance (1997 and 2002 update) afforded CPX a Class I recommendation (i.e., "conditions for which there is evidence 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 HF who are being considered for heart transplantation." There was no associated level of evidence with this recommendation. The more recent HF-specific clinical guideline (2005 and 2009 update) changed the recommendation for CPX to Class IIa (i.e., "indicates that the weight of evidence/opinion is in favor of usefulness/efficacy") as "being reasonable to identify high-risk patients presenting with HF who are candidates for cardiac transplantation or other advanced treatments". The level of evidence associated with this recommendation was "B" (i.e., "a limited number of randomized controlled trials with small numbers of studies or observational registries"). No rationale was provided for the change in CPX class recommendation (i.e., from I to IIa).
Despite the change in class recommendation, CPX utilization in patients with HF has been viewed, at least in concept, as a widely available clinical standard of care for more than a decade. There are several caveats to previous CPX class recommendation and level of evidence designations that may not be readily apparent: 1) The reason CPX continues to be considered valuable in patients with HF who are being considered for heart transplantation or other advanced treatments is because of the assumption that this procedure provides a robust ability to predict adverse events, in particular, mortality. During the last decade, the value of CPX in predicting mortality in HF has been confirmed consistently by numerous observational studies, even in cohorts not being considered for transplantation or other advanced treatments. However, the view of the prognostic and, therefore, primary clinical utility of CPX remains narrowly focused on those being considered for end-stage interventions (e.g., transplantation); 2) In both previous AHA/ACC clinical practice guidelines and their revisions, peak oxygen consumption (V̇O2) was the only variable considered for the assessment of transplant candidacy, advanced treatments, or gauging therapeutic efficacy — despite the fact that a host of other potentially valuable CPX variables are readily obtainable; and 3) Given that heart transplantation continues to be reserved for patients diagnosed as having HF and reduced ejection fraction (HFrEF), the recommendations provided in these clinical guidelines were meant to apply exclusively to this subgroup. Thus, none of the CPX proposed recommendations provided in these guidelines apply to patients with HF and preserved ejection fraction (HFpEF). The body of scientific evidence and perceived clinical utility and value of CPX currently are incongruent. Stated succinctly, previous clinical practice guidelines perpetuate the following premise: Peak V̇O2 is the only CPX variable that holds prognostic value, only in patients with HFrEF. Scientific evidence, however, indicates that the value and clinical applications of CPX in the HF population are much richer and broader, respectively.
There have been many advances in the years since the 1997 and 2002 updates to the AHA/ACC Guidelines for Exercise Testing were published. The same can be said for the 2005 and 2009 updates to the guidelines for HF diagnosis and management. The clinical, pharmacologic, and surgical management of the HF population continues to expand and evolve, and, although prognosis in this chronic disease population remains disconcerting, it has improved substantially. Moreover, the unique pathophysiology, presentation, and clinical trajectory of patients diagnosed with HFrEF as compared with those with HFpEF are being recognized increasingly. Lastly, the body of evidence investigating the clinical utility of CPX with respect to prognostic, diagnostic, and therapeutic efficacy assessments continues to increase. As such, a new paradigm for CPX use and interpretation in HF is warranted. We hypothesize that scientific evidence for this new paradigm is substantial, proving that clinical utilization, class recommendations, and the associated level of evidence for CPX in the HF population can be expanded significantly.
Our group initiated a multicenter consortium in 2002 in an effort to gain better insights into the role of CPX in HF. Combining data from established centers allow important hypotheses to be tested with an appropriate sample size (currently n > 2500) and, thus, statistical power. The multicenter consortium has contributed significantly to the worldwide body of work related to CPX utility in HF. The collective body of available evidence supports the hypothesis that a new CPX paradigm is warranted, one that involves: 1) expanding the list of relevant CPX variables based on scientific evidence; 2) incorporating diagnostic, prognostic, and therapeutic efficacy applications; and 3) expanding utilization of CPX beyond patients with HFrEF being considered for heart transplantation.
Many of the studies discussed in subsequent sections of this article focus on results from the multicenter consortium, lending support to the hypothesis that a new CPX paradigm in HF is justifiable. Updated/revised/expanded class recommendations and associated levels of evidence will be presented with the following questions in mind: 1) Does CPX continue to provide prognostic value in patients with HF? 2) Would there be value to expanding the clinical applications of CPX to all patients with HF, as opposed to only those being evaluated actively for transplantation? 3) Should the list of CPX variables for prognostic assessment be expanded beyond peak V̇O2? 4) Are key CPX variables responsive to various interventions, allowing for a valid and reliable gauge of therapeutic efficacy? 5) What CPX variables(s) should be included in the assessment of therapeutic efficacy? 6) Are there diagnostic applications for CPX in patients with HF? and 7) Should CPX be used clinically in both the HFrEF and HFpEF populations?
Abstract and Introduction
Abstract
American Heart Association/American College of Cardiology class recommendations and associated level of evidence for cardiopulmonary exercise testing (CPX) have been put forth. A new paradigm is proposed for CPX use and interpretation in heart failure (HF). Evidence for this new paradigm will be provided, showing that clinical utilization, class recommendations, and the associated level of evidence for CPX in the HF population can be expanded significantly.
Introduction
The American Heart Association (AHA) and the American College of Cardiology (ACC) use a rigorous system for determining class recommendation and associated level of evidence for practice patterns, serving as the basis for their clinical guidelines. A detailed description of this system is provided elsewhere. The AHA/ACC has used this class recommendation/level of evidence system for the use of cardiopulmonary exercise testing (CPX) in patients with heart failure (HF). Initial guidance (1997 and 2002 update) afforded CPX a Class I recommendation (i.e., "conditions for which there is evidence 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 HF who are being considered for heart transplantation." There was no associated level of evidence with this recommendation. The more recent HF-specific clinical guideline (2005 and 2009 update) changed the recommendation for CPX to Class IIa (i.e., "indicates that the weight of evidence/opinion is in favor of usefulness/efficacy") as "being reasonable to identify high-risk patients presenting with HF who are candidates for cardiac transplantation or other advanced treatments". The level of evidence associated with this recommendation was "B" (i.e., "a limited number of randomized controlled trials with small numbers of studies or observational registries"). No rationale was provided for the change in CPX class recommendation (i.e., from I to IIa).
Despite the change in class recommendation, CPX utilization in patients with HF has been viewed, at least in concept, as a widely available clinical standard of care for more than a decade. There are several caveats to previous CPX class recommendation and level of evidence designations that may not be readily apparent: 1) The reason CPX continues to be considered valuable in patients with HF who are being considered for heart transplantation or other advanced treatments is because of the assumption that this procedure provides a robust ability to predict adverse events, in particular, mortality. During the last decade, the value of CPX in predicting mortality in HF has been confirmed consistently by numerous observational studies, even in cohorts not being considered for transplantation or other advanced treatments. However, the view of the prognostic and, therefore, primary clinical utility of CPX remains narrowly focused on those being considered for end-stage interventions (e.g., transplantation); 2) In both previous AHA/ACC clinical practice guidelines and their revisions, peak oxygen consumption (V̇O2) was the only variable considered for the assessment of transplant candidacy, advanced treatments, or gauging therapeutic efficacy — despite the fact that a host of other potentially valuable CPX variables are readily obtainable; and 3) Given that heart transplantation continues to be reserved for patients diagnosed as having HF and reduced ejection fraction (HFrEF), the recommendations provided in these clinical guidelines were meant to apply exclusively to this subgroup. Thus, none of the CPX proposed recommendations provided in these guidelines apply to patients with HF and preserved ejection fraction (HFpEF). The body of scientific evidence and perceived clinical utility and value of CPX currently are incongruent. Stated succinctly, previous clinical practice guidelines perpetuate the following premise: Peak V̇O2 is the only CPX variable that holds prognostic value, only in patients with HFrEF. Scientific evidence, however, indicates that the value and clinical applications of CPX in the HF population are much richer and broader, respectively.
There have been many advances in the years since the 1997 and 2002 updates to the AHA/ACC Guidelines for Exercise Testing were published. The same can be said for the 2005 and 2009 updates to the guidelines for HF diagnosis and management. The clinical, pharmacologic, and surgical management of the HF population continues to expand and evolve, and, although prognosis in this chronic disease population remains disconcerting, it has improved substantially. Moreover, the unique pathophysiology, presentation, and clinical trajectory of patients diagnosed with HFrEF as compared with those with HFpEF are being recognized increasingly. Lastly, the body of evidence investigating the clinical utility of CPX with respect to prognostic, diagnostic, and therapeutic efficacy assessments continues to increase. As such, a new paradigm for CPX use and interpretation in HF is warranted. We hypothesize that scientific evidence for this new paradigm is substantial, proving that clinical utilization, class recommendations, and the associated level of evidence for CPX in the HF population can be expanded significantly.
Our group initiated a multicenter consortium in 2002 in an effort to gain better insights into the role of CPX in HF. Combining data from established centers allow important hypotheses to be tested with an appropriate sample size (currently n > 2500) and, thus, statistical power. The multicenter consortium has contributed significantly to the worldwide body of work related to CPX utility in HF. The collective body of available evidence supports the hypothesis that a new CPX paradigm is warranted, one that involves: 1) expanding the list of relevant CPX variables based on scientific evidence; 2) incorporating diagnostic, prognostic, and therapeutic efficacy applications; and 3) expanding utilization of CPX beyond patients with HFrEF being considered for heart transplantation.
Many of the studies discussed in subsequent sections of this article focus on results from the multicenter consortium, lending support to the hypothesis that a new CPX paradigm in HF is justifiable. Updated/revised/expanded class recommendations and associated levels of evidence will be presented with the following questions in mind: 1) Does CPX continue to provide prognostic value in patients with HF? 2) Would there be value to expanding the clinical applications of CPX to all patients with HF, as opposed to only those being evaluated actively for transplantation? 3) Should the list of CPX variables for prognostic assessment be expanded beyond peak V̇O2? 4) Are key CPX variables responsive to various interventions, allowing for a valid and reliable gauge of therapeutic efficacy? 5) What CPX variables(s) should be included in the assessment of therapeutic efficacy? 6) Are there diagnostic applications for CPX in patients with HF? and 7) Should CPX be used clinically in both the HFrEF and HFpEF populations?
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