Pressure-flow responses to exercise in aortic stenosis, mitral regurgitation and diastolic dysfunction

Abstract

Background: Haemodynamic exercise testing is important for evaluating patients with dyspnoea on exertion and preserved ejection fraction. Despite very different pathologies, patients with pressure (aortic stenosis (AS)) and volume (mitral regurgitation (MR)) overload and diastolic dysfunction after recent acute myocardial infarction (AMI) reach similar filling pressure levels with exercise. The pressure-flow relationships (the association between change in cardiac output (∆CO) and change in pulmonary arterial wedge pressure (∆PAWP) may provide insight into haemodynamic adaptation to exercise in these groups.

Methods and results: One hundred sixty-eight subjects aged >50 years with a left ventricular ejection fraction of ≥50% underwent invasive exercise testing. They were enrolled in four different studies: AS (40 patients), AMI (52 patients), MR (43 patients) and 33 healthy subjects. Haemodynamic data were measured at rest, at 25 W, 75 W and at peak exercise. In all groups, PAWP increased with exercise. The greatest increase was observed in patients with AMI (from 12.7±3.9 mm Hg to 33.1±8.2 mm Hg, p<0.0001) and patients with AS (from 11.8±3.9 mm Hg to 31.4±6.1 mm Hg, p<0.0001), and the smallest was observed in healthy subjects (from 8.3±2.4 mm Hg to 21.1±7.5 mm Hg, p<0.0001). In all groups, the relative pressure increase was greatest at the beginning of the exercise. CO increased most in healthy patients (from 5.3±1.1 to 16.0±3.0 L/min, p<0.0001) and least in patients with AS (from 5.3±1.2 L/min to 12.4±2.6 L/min, p<0.0001). The pressure-flow relationships (∆PAWP/∆CO) and differed among groups (p=0.02). In all groups, the pressure-flow relationship was steepest in the initial phase of the exercise test. The AMI and AS groups (2.3±1.2 mm Hg/L/min and 3.0±1.3 mm Hg/L/min, AMI and AS, respectively) had the largest overall pressure-flow relationship; the healthy group had the smallest initially and at peak exercise (1.3±1.1 mm Hg/L/min) followed by MR group (1.9±1.4 mm Hg/L/min).

Conclusion: The pressure-flow relationship was steepest in the initial phase of the exercise test in all groups. The pressure-flow relationship differs between groups.

Trial registration numbers: NCT01974557, NCT01046838, NCT02961647 and NCT02395107.

Keywords: Aortic stenosis; Heart Failure, Diastolic; Mitral regurgitation; Myocardial Infarction.

Figure 1

Pictures of the haemodynamic tracings from a patient with mitral regurgitation. Left column shows measurements performed at rest; right column shows measurements performed during exercise; top row shows heart rhythm (green), pulse oximetry (blue), pulmonary artery pressure (yellow), right atrial pressure (blue) and non-invasive blood pressure (red). Middle row shows the individual thermodilution cardiac output tracings. Bottom row shows heart rhythm (green), respiratory tracing (top yellow) and pulmonary arterial wedge pressure (bottom yellow). Note the marked V wave during exercise.

Figure 2

Box plot showing (A) peak PAWP in the healthy, AMI, MR and AS groups. The dotted line represents a PAWP cut-off at 25 mm Hg. (B) Absolute ∆PAWP and (C) ∆CO. All data points are shown. Error bars reflect the minimum and maximum values. *P<0.05 vs healthy, ‡P<0.05 vs AMI, †P<0.05 vs MR. Between-group differences were tested by analysis of variance and Tukey’s multiple comparisons test. ∆CO, change in cardiac output; ∆PAWP, change in pulmonary arterial wedge pressure; AMI, acute myocardial infarction; AS, aortic stenosis; MR, mitral regurgitation; PAWP, pulmonary arterial wedge pressure.

Figure 3

Slope of the increase in PAWP relative to CO for the healthy (circle), AMI (square), MR (triangle) and AS (inverted triangle) groups at rest, 25 W, 75 W and peak exercise. The dotted line represents a PAWP/CO cut-off at 2 mm Hg/L. Data points represent mean group values. Error bars reflect the SD. Between-group differences were tested by multivariate analysis of variance with repeated measures (Hotelling-Lawley trace) and adjusted for age, gender and body mass index. AMI, acute myocardial infarction; AS, aortic stenosis; CO, cardiac output; MR, mitral regurgitation; PAWP, pulmonary arterial wedge pressure.

Figure 4

Slope of the increase in mPAP relative to CO for the healthy (circle), AMI (square), MR (triangle) and AS (inverted triangle) groups at rest, 25 W, 75 W and peak exercise. The dotted line represents an mPAP/CO cut-off at 3 mm Hg/L. Data points represent mean group values. Error bars reflect the SD. Between-group differences were tested by multivariate analysis of variance with repeated measures (Hotelling-Lawley trace) and adjusted for age, gender and body mass index. AMI, acute myocardial infarction; AS, aortic stenosis; CO, cardiac output; mPAP, mean pulmonary arterial pressure; MR, mitral regurgitation; PAWP, pulmonary arterial wedge pressure.