Response to Letter by Smiseth and Nagueh Regarding "The Role of Diastolic Stress Testing in the Evaluation for HFpEF: A Simultaneous Invasive-Echocardiographic Study”

We thank Drs. Smiseth and Nagueh for their interest in our recent publication testing the role of invasive and noninvasive diastolic stress testing in the evaluation of heart failure with preserved ejection fraction (HFpEF).¹ The authors point out how the hemodynamic data collected in our study provides a unique opportunity to understand more about the determinants of exercise capacity in patients with HFpEF. We agree, and in fact we have published a different article from this cohort specifically devoted to that very question.²

The goal of this paper was not to characterize the pathophysiology, but to examine the role of exercise testing in diagnosis of HFpEF.¹ As the authors recommended, we have re-analyzed our sample using the algorithm from Figure 8B from the ASE/EACVI document.³ Like the algorithm from Figure 8A that we tested in our study,¹ this scheme displayed poor sensitivity for HFpEF (42%). Even if we restrict the analysis to the 32 HFpEF subjects in our study with high filling pressures at rest, the algorithm from Figure 8B again displayed poor sensitivity (63%).

The authors suggest that scatterplots correlating hemodynamics and echocardiographic indices with exercise performance would have been informative. That was not the purpose of our paper.¹ However, those questions were examined in our earlier report.² As we demonstrated in that paper, exercise capacity (peak oxygen consumption) was inversely correlated with directly-measured filling pressures during exercise (r= −0.44, p<0.001) as well as pulmonary artery pressures (r= −0.45, p<0.001).² In contrast, resting E/e’ ratio was only modestly correlated with peak aerobic capacity (r= −0.30, p=0.01).

Drs. Smiseth and Nagueh suggest that invasive diastolic stress testing is not practical and is restricted to a very small number of centers. There are at least 30 medical centers in the United States that we are aware of currently performing invasive hemodynamic exercise tests for the evaluation of unexplained dyspnea. Over 200 exercise catheterizations are performed each year at our institution alone. The added equipment needed for this purpose is minimal and inexpensive, and in past eras, was available in most diagnostic catheterization labs. Our study cohort was not highly selected, but was drawn from consecutive patients referred to our laboratory with unexplained exertional dyspnea, reflecting what is seen in the community.

Finally, the necessity of invasive exercise testing for a substantial portion of patients with dyspnea is neither an assumption nor is it premature, since this is a conclusion that is supported by empirical data obtained in a prospective trial.¹ We agree that further study and validation may be worthwhile, particularly to verify the utility and accuracy of exercise echocardiography, as previous studies from other groups have reported less robust findings using noninvasive imaging as compared to our data.^{4, 5} Accurate diagnosis in patients presenting with dyspnea can provide a multitude of valuable, patient-centered benefits that positively affect the care we deliver. This often requires careful hemodynamic measurements during exercise in addition to rest, and these are too frequently not performed at all, invasively or noninvasively.