Response by Hoedemakers et al to Letter Regarding Article, “mPAP/CO Slope and Oxygen Uptake Add Prognostic Value in Aortic Stenosis”

Abstract

In Response: We have read with interest the comments by Dr Jha on our study. In our population (n=143) with aortic valve stenosis, 30 patients (21%) exhibited a high gradient (maximal transvalvular velocity or V max >4 m/s), while 113 (79%) had a low gradient. In the low-gradient group, 36 patients or 25% of the overall population had a low-flow status (stroke volume index <35 mL/m²), which is on the high end probably because such patients are more frequently referred for exercise echocardiography. The others were 10 patients with normal flow and 67 with moderate aortic valve stenosis (aortic valve area >1.0 cm²). Only 7 patients had stroke volume indices >35 mL/m 2 in combination with a systolic blood pressure >140 mm Hg. Dr Jha further emphasizes the importance of pulmonary artery wedge pressure (PAWP). Importantly, in our study, no invasive measurements were available and PAWP can be estimated at rest from E/e' values. The regression formula to calculate PAWP from E/e' has important limitations and is likely less accurate during exercise (where there is often E-A fusion, especially at maximal exercise). For the interest of Dr Jha, in our population, PAWP was estimated 18 mm Hg at low-intensity exercise and 17 mm Hg at peak exercise , based on a median E/e' of 13 and 12, respectively. Using these numbers would result in a negative PAWP−cardiac output slope, which is unphysiologic and underlines the limitations of echocardiography to quantitatively estimate PAWP during exercise. In the absence of clear pulmonary vascular or lung disease, evolutions in the mean pulmonary arterial pressure during exercise largely reflect changes in PAWP. In fact, it has been demonstrated in patients with severe aortic stenosis that invasively measured PAWP did not correlate with simultaneously measured E/e' during exercise. 1 The exercise-induced increase in PAWP was not (or minimally) reflected in the E/e' change. Nevertheless , we agree that the importance of PAWP assessment in addition to mean pulmonary arterial pressure should not be disregarded. PAWP−cardiac output is an earlier step in the retrograde pressure-cascade of cardiac damage and is particularly helpful in differentiating pre-versus postcapillary or combined pathology, preferably by invasive measurement. The additional benefit of mean pulmonary arterial pressure−cardiac output is that it gives an impression of further disease progression and does not neglect a precapillary or pulmonary component. We discussed the topic of intrinsic myocardial dys-function in a previous paper, finding that it is indeed highly prevalent in this population. 2 Nonetheless, coronary artery disease is not always the cause of this myo-cardial dysfunction. Indeed, many patients with heart failure with preserved ejection fraction without obstructive coronary artery disease demonstrate a blunted or absent systolic reserve. Patients with severe aortic ste-nosis included in this study were either asymptomatic or had nonspecific symptoms, and only 3 of the latter presented with chest discomfort. Moreover, all patients receiving coronary intervention within 3 months of their cardiopulmonary exercise testing were excluded from the study specifically to reduce an inherent bias of con-comitant significant coronary artery disease. A sensitivity analysis without aortic valve replacement in the end points and a validation cohort supported the findings. ARTICLE INFORMATION Affiliations