In this study, we examined the performance of the H2FPEF and HFA-PEFF scores for predicting exercise capacity and echocardiographic measures during exercise stress echocardiography. We observed that the HFA-PEFF score displayed relatively low feasibility because of the requirement of natriuretic peptide levels while the H2FPEF score displayed perfect feasibility. We further demonstrated that both H2FPEF and HFA-PEFF algorithms predicted lower LV systolic and diastolic function, higher estimated LV filling pressure, lower CO, and reduced RV systolic function during peak ergometry exercise. Despite the requirement of fewer input variables, the H2FPEF score provided a good discriminatory ability for identifying poor exercise capacity among patients with dyspnea while the HFA-PEFF score did not. These data provide new insights into the role of the H2FPEF and HFA-PEFF scores for predicting exercise intolerance and hemodynamics correlates in patients presenting with exertional dyspnea.
Abnormal Exercise Hemodynamics and Exercise Intolerance in HFpEF.
Exercise intolerance is a hallmark of patients with HFpEF and studies to date have uniformly reported that peak VO2 is depressed in HFpEF.2,3,15−18 Reduced exercise capacity is associated with symptoms of dyspnea and poor quality of life, making it an important therapeutic target in this syndrome.3,19 While multiple mechanisms can contribute to exercise intolerance in HFpEF, including abnormalities in the heart, lungs, and the periphery, pathologic increases in cardiac filling pressures developed during exercise stress may play an important role in limiting exercise performance in HFpEF.2,3,20−22 As expected, the current study demonstrated that exercise capacity was reduced in patients with HFpEF compared to control subjects as evidenced by lower peak exercise workload, shorter exercise duration, and depressed peak oxygen consumption. Compared to controls, patients with HFpEF displayed lower mitral e’ and s’ tissue velocities, higher E/e’ ratio, reduced CO, and lower TV s’ during peak exercise and the severities of these abnormalities were consistently associated with depressed exercise capacity. These data confirm that abnormal exercise hemodynamics and reduced CO reserve contribute to exercise intolerance in patients with HFpEF.
The H2FPEF and HFA-PEFF Scores
Two multiparametric scoring systems have been proposed to help diagnose HFpEF among patients with dyspnea. The H2FPEF score is developed among patients with unexplained dyspnea using the currently-recommended gold standard test (i.e., invasive exercise hemodynamic testing), and combines clinical characteristics and echocardiographic measures.5 The HFA-PEFF score is a consensus-based approach that employs more complex scoring systems based on echocardiographic indices and natriuretic peptide levels.6 As expected, the H2FPEF score was obtainable in all patients while the HFA-PEFF score could not be calculated in 12% of patients due to the lack of natriuretic peptide data. Although evaluation of natriuretic peptides is the key in the diagnostic approach in HFpEF, they may not be measured in all patients with dyspnea.6 On the other hand, echocardiography is performed in essentially all patients in whom there is clinical suspicion for HFpEF.23 The current study also demonstrated that the HFA-PEFF scores categorized more patients into high HFpEF probability compared to the H2FPEF score. Further studies are required to directly compare the diagnostic value between two scores using the gold standard of invasive exercise hemodynamic testing.
The H2FPEF and HFA-PEFF Scores and Exercise Capacity
In addition to the diagnostic value, recent studies have shown the association between the two algorithms and clinical outcomes in patients with HFpEF.7–10 However, few data are available regarding whether these diagnostic schemes could predict aerobic capacity in HFpEF. In this study, we found that the H2FPEF score was associated with reduced exercise capacity as assessed by both peak VO2 and exercise duration, which is consistent with a previous study.24 In contrast, while the HFA-PEFF score was modestly correlated with exercise duration (r=-0.26), it was unrelated to peak VO2. We further demonstrated that the H2FPEF score identified reduced peak VO2, but the HFA-PEFF algorithm did not. The plausible reason for this may be related to the inclusion of both clinical and echocardiographic variables in the H2FPEF score, but not in the HFA-PEFF score. It is clear that HFpEF is associated with comorbidities, including obesity, hypertension, diabetes, and AF.16–19 Previous studies have demonstrated that higher BMI and AF are related to decreased exercise capacity in patients with HFpEF.16,18,25,26 Indeed, the present study showed that individual component of H2FPEF score was associated with peak VO2. In contrast, only LV longitudinal strain and BNP were correlated with peak oxygen consumption among the components of the HFA-PEFF score. It is also worth pointing out that the weighted H2FPEF score is more predictive of peak VO2 than the individual components. This suggests the usefulness of the H2FPEF score not only for diagnosing HFpEF but also for predicting exercise capacity.
The association between the H2FPEF score and peak VO2 may raise the question of whether therapies targeting the components of the score could improve aerobic capacity in patients with HFpEF. Obesity may be a promising target given its high prevalence and pathophysiologic significance.18 Kitzman and colleagues demonstrated that weight loss induced by caloric restriction or aerobic exercise training improved peak VO2, reduced LV mass and inflammatory markers, and enhanced quality of life in patients with obese HFpEF.27 Bariatric surgery has been demonstrated to improve functional capacity in obese patients with HF with reduced EF.28 Obesity and increased adiposity may better response to sodium-glucose co-transporter 2 inhibitors by reducing plasma volume and visceral and epicardial fat. A substantial proportion of patients with HFpEF develop AF, and they suffer from more biatrial dysfunction, worse functional capacity, RV dysfunction, and increased risk of death.16,29,30 Catheter ablation may be effective to reverse or at least prevent the adverse consequences of AF,31,32 but this should be tested in prospective trials. Intensive treatment of isolated hypertension was shown to be effective for the prevention of the development of HF.33 Further studies are required to test whether it will prevent or mitigate the progression of HFpEF.
Limitations
The current study has several limitations. All participants were referred for exercise stress echocardiography. This might introduce selection bias. The sample size was relatively small, which could bias overall results. The control group was not truly normal as they were referred for exercise stress echocardiography in the evaluation of exertional dyspnea and had multiple comorbidities, which could also bias the results. LV longitudinal strain was determined using apical four-chamber views.