Stress echocardiography combined with cardiopulmonary exercise testing: Opening a new window into diagnosis of heart failure with preserved ejection fraction

Approximately half of all patients with heart failure have preserved ejection fraction, a condition whose trajectory in prevalence is increasing. According to consensus recommendations, a diagnosis of heart failure with preserved ejection fraction (HFpEF) can be obtained when three requirements are met simultaneously: signs and symptoms of heart failure; preserved left ventricular (LV) global systolic performance (ejection fraction by echocardiography >50% and LV end-systolic volume <97ml/m) in the presence of impaired LV relaxation and compliance. An increase in LV filling pressure is an important haemodynamic signature that triggers exercise limitation and symptoms. Some HFpEF patients, however, may be misclassified, because they have virtually normal LV diastolic function and filling pressure at rest, compared with controls. Traditional echocardiographic indices have been insensitive for the diagnosis of HFpEF because they have tried to identify patients with breathlessness during exercise, using only resting diagnostic criteria. Diagnosis may therefore remain challenging, especially in the earlier stages when symptoms occur just during exercise and incoming dyspnoea is a sensitive but not specific marker to accomplish a diagnosis. So, exercise appears the ideal physiological condition to monitor simultaneously cardiac filling pressure by Doppler echocardiography and symptoms by cardiopulmonary exercise testing (CPET), possibly commuting the suspicion in a true diagnosis. How can this be obtained and how may the information provided by the two tests integrate with each other? In a series of 86 subjects with normal LV ejection fraction and exertional dyspnoea, Nedeljkovic and coworkers intriguingly address how much exercise stress echo and CPET may be synergistic in unmaking early HFpEF clinical manifestations. Previous trials in this area have been limited to an isolated echo-Doppler stress test analysis assessing the diastolic response in patients with established rather than suspected HFpEF diagnosis. In addition, the few studies combining CPET did report peak oxygen consumption (VO2) only, 8,13 without a comprehensive evaluation of gas exchange measures reflective of cardiac functional reserve (oxygen pulse) and ventilatory efficiency (slope of rate of increase in ventilation to carbon dioxide production (VE/VCO2)). The only prespecified criteria for a diagnosis of HFpEF was a ratio of two-dimensional (2D) echo Doppler early mitral flow (E) and tissue Doppler imaging of early mitral annulus movement (e0) at peak exercise greater than 15, which although not a validated standard for signalling an abnormal increase in LV filling pressure during exercise, represents the cut-off identified by most. In the normal heart, e0 changes with rapid motion of mitral annulus along the LV long axis and occurs almost concomitant with the mitral E wave. With impairment in LV relaxation and compliance, E inflow is slowed and e0 is reduced and delayed. When diastolic dysfunction results in an increased left atrial pressure, E wave velocity increases and the augmented E/e0 indicates an increase in filling pressure providing a non-invasive indicator of diastolic heart failure. Thus, it should be realised that in patients with diastolic dysfunction that has not yet caused an increase in left atrial pressure, E/e0 is normal at rest, whereas it increases only during a ‘diastolic stress’, such as exercise. Despite this rationale and quite a large amount of evidence, most recent reports suggest that E/e0 is