Assess exercise-induced changes in diastolic trans-mitral blood flow in younger and older healthy volunteers and subjects with pulmonary hypertension (PH).

Dyspnea on exertion is a common manifestation of both systolic and diastolic heart failure. Thorough assessment of systolic and diastolic function at rest and with exercise is essential for understanding and characterizing cardiac function. The ability to use exercise stress cardiac MR to characterize left ventricular systolic function has been previously demonstrated (1). The feasibility of assessing diastolic function in healthy volunteers using exercise and pharmacologic stress cardiac MR has also been previously demonstrated (2,3).

Patients with PH have increased right ventricular pressure which can inhibit left ventricular diastolic filling and cause diastolic dysfunction. Prior studies have also shown that diastolic function changes with normal aging (4). In this study we performed exercise stress cardiac MR to assess changes in diastolic function between young healthy volunteers (age < 50), older healthy volunteers (age >50), and subjects with PH.

Subjects: 17 healthy subjects under the age of 50 (age 28.3±7.5, 6 male/11 female), 6 healthy subjects over the age of 50 (age 62.3±6.4, 1 male/5 female) and 6 patients with pulmonary hypertension (age 49.0±21.5,1 male/5 female) were prospectively recruited according to a HIPAA-compliant, IRB-approved protocol.

MRI: Exercise cardiac MR was performed on a 1.5 T scanner (HDx and 450W, GE Healthcare, Waukesha, WI) using an MRI-compatible exercise device (5) that allowed subjects to exercise while lying supine on the scanner (Figure 1). Flow across the mitral valve was assessed using 2D phase contrast (PC) MRI (FOV=370x260mm2; matrix= 256x128); TR/TE=6.1/3.7ms; FA=30°; ASSET=2; VENC=100cm/s) with the plane set parallel to the mitral annulus at the tips of the MV leaflets during diastole. Exercise was performed for at least 3 minutes at a constant workload (36.1±7.5W). To minimize motion artifacts, acquisition of flow measurements was performed during a 15 second breath-hold immediately following cessation of exercise.

Analysis: CV Flow (Version 3.3, Medis, Leiden, the Netherlands) was used to analyze 2D PC images. Rest and exercise peak E and A velocities and E/A ratios were recorded from the transmitral inflow-time curves (Figure 2). The Student’s t-test was utilized to assess if differences between rest and exercise as well as differences between healthy subjects and subjects with PH were statistically significant.

Rest and exercise stress MV flow data was successfully acquired in all subjects and summarized in Figure 3. At rest, peak A wave velocities and E/A ratios were significantly lower in PH patients (70.93±27.8; 1.0±0.3) and older healthy volunteers(91.9±26.6; 1.0±0.2) when compared to younger healthy volunteers (55.7±18.8; 1.6±0.4). E, A, and E/A ratios were not significantly different between subject groups with stress.As expected, the results at rest show significantly higher peak A wave velocities and significantly lower E/A ratios for older healthy volunteers and PH patients when compared to younger healthy volunteers. These results support previously demonstrated changes in diastolic function with normal aging (3) and also support the association of PH and diastolic dysfunction. The exercise stress data also shows lower E/A ratios for older healthy volunteers and PH patients compared to younger healthy volunteers, however these differences were not significant, possibly due to the small sample sizes of the older healthy volunteers and PH patients or relatively low workload. Interestingly, at similar workload, patients with pulmonary hypertension had a significantly higher heart rate than younger and older healthy volunteers.This study demonstrates that quantitative assessment of exercise stress transmitral flow in healthy volunteers and PH patients is feasible.