Leveraging Cardiopulmonary Exercise Testing to Identify and Treat Pulmonary Hypertension in Heart Failure

Complaints of exertional intolerance and dyspnea initiate a cadre of medical examinations to diagnose left ventricular impairments characteristic of left-sided heart failure (HF). In many cases, the progression and efficacy of pharmacologic treatment of HF focus on quantifying left ventricular functional and structural responses. Accordingly, the emphasis of the broader systemic consequences of HF may be underappreciated; in particular, the detection of pulmonary hypertension is often overlooked. Lalande and colleagues’ (1) eloquent review of the current literature identifies the mechanistic contributors of multiorgan dysfunction in patients with HF and provides a much-needed spotlight on pulmonary impairments resulting from the HF syndrome. The authors also appropriately highlight the global effects of central and peripheral pathophysiology on cardiorespiratory fitness (CRF). Cardiopulmonary exercise testing (CPX) is the gold standard method for quantifying CRF (peak oxygen consumption (V̇O2peak)), consistently demonstrated to be among the strongest predictors of adverse events and mortality in patients with HF. This simple, widely accessible, noninvasive, and cost-effective tool provides a telling assessment of the integrated response of multiple organ systems to a symptom-limited exercise challenge. A reduction in V̇O2peak in left-sided HF is indicative of an impaired cardiac output response to exercise, and V̇O2peak values <10 mL·kg−1·min−1 in advanced HF may warrant aggressive interventions. Furthermore, a wealth of evidence showcases the multidimensional applications of CPX and its ability to provide additional information regarding the presence of elevated pulmonary pressures (2). Ventilatory efficiency, quantified by the minute ventilation (V̇E) to the carbon dioxide production (V̇CO2) slope, reflects the relation between pulmonary ventilation and perfusion during exercise. In cases of advanced left-sided HF that causes a retrograde increase in pulmonary pressures, a decrease in pulmonary perfusion occurs relative to pulmonary ventilation and results in an elevated V̇E/V̇CO2 slope. Patients with a V̇E/V̇CO2 slope ≥45 particularly have been shown to be at an increased risk for mortality. Moreover, values ≥45 indicate pulmonary hypertension that increases the risk of developing right-sided ventricular failure. Given the close relation between left ventricular dysfunction with reduced V̇O2peak and elevated V̇E/V̇CO2 in the presence of pulmonary hypertension, we previously have proposed the use of CPX to identify intracardiac multimorbidity (3). Accordingly, information gained through CPX could facilitate the identification of central impairments and guide implementation of optimal pharmacologic and lifestyle interventions. The literature examining the effects of exercise in patients with left-sided HF and pulmonary hypertension clearly demonstrates that the benefits of exercise outweigh the risks. However, current evidence on the extent to which moderate aerobic exercise training can modify pulmonary hemodynamics is less clear (4). Rather, peripheral adaptations, such as improved skeletal muscle characteristics, enhanced endothelial function, increased vagal tone, and reduced systemic inflammation, contribute to improved CRF after a training intervention (4). Performing inspiratory muscle training has also been shown to lead to improvements in peripheral blood flow to exercising skeletal muscle as a result of decreased sympathetic activity and has contributed to reduced left ventricular diastolic pressure and increased systolic pressure, and decreased right ventricular hypertrophy and vagal tone in animal model interventions (4). Similar to aerobic exercise training, inspiratory muscle training alone has been shown to improve V̇O2peak as well as the V̇E/V̇CO2 slope (5). Therefore, CPX can be thought of as not only a robust prognosticator and measure to identify pulmonary hypertension in patients with HF, but also be incorporated into the tracking of treatment efficacy within investigative trials and clinical settings. Cemal OzemekRoss ArenaDepartment of Physical Therapy College of Applied Health Sciences University of Illinois at Chicago Chicago, ILBo FernhallIntegrative Physiology Laboratory Department of Kinesiology and Nutrition University of Illinois at Chicago Chicago, IL