Exercise cardiac MRI unmasks right ventricular dysfunction in acute hypoxia and chronic pulmonary arterial hypertension

Abstract

Coupling of right ventricular (RV) contractility to afterload is maintained at rest in the early stages of pulmonary arterial hypertension (PAH), but exercise may unmask depleted contractile reserves. We assessed whether elevated afterload reduces RV contractile reserve despite compensated resting function using noninvasive exercise imaging. Fourteen patients with PAH (mean age: 39.1 yr, 10 women and 4 men) and 34 healthy control subjects (mean ageL 35.6 yr, 17 women and 17 men) completed real-time cardiac magnetic resonance imaging during submaximal exercise breathing room air. Control subjects were then also exercised during acute normobaric hypoxia (fraction of inspired O: 12%). RV contractile reserve was assessed by the effect of exercise on ejection fraction. In control subjects, the increase in RV ejection fraction on exercise was less during hypoxia ( P = 0.017), but the response of left ventricular ejection fraction to exercise did not change. Patients with PAH had an impaired RV reserve, with half demonstrating a fall in RV ejection fraction on exercise despite comparable resting function to controls (PAH: rest 53.6 ± 4.3% vs. exercise 51.4 ± 10.7%; controls: rest 57.1 ± 5.2% vs. exercise 69.6 ± 6.1%, P < 0.0001). In control subjects, the increase in stroke volume index on exercise was driven by reduced RV end-systolic volume, whereas patients with PAH did not augment the stroke volume index, with increases in both end-diastolic and end-systolic volumes. From baseline hemodynamic and exercise capacity variables, only the minute ventilation-to-CO output ratio was an independent predictor of RV functional reserve ( P = 0.021). In conclusion, noninvasive cardiac imaging during exercise unmasks depleted RV contractile reserves in healthy adults under hypoxic conditions and patients with PAH under normoxic conditions despite preserved ejection fraction at rest. NEW & NOTEWORTHY Right ventricular (RV) reserve was assessed using real-time cardiac magnetic resonance imaging in patients with pulmonary arterial hypertension and in healthy control subjects under normobaric hypoxia, which has been previously associated with acute pulmonary hypertension. Hypoxia caused a mild reduction in RV reserve, whereas chronic pulmonary arterial hypertension was associated with a marked reduction in RV reserve.

Right ventricular dyssynchrony during hypoxic breathing but not during exercise in healthy subjects: a speckle tracking echocardiography study

“…There was no significant increase in RVEDA, confirming previous observations in healthy subjects exposed to acute or subacute hypobaric hypoxia (Allemann et al, 2012;Boussuges et al, 2000) or 1 h of normobaric hypoxic breathing (Huez et al, 2005;Kjaergaard et al, 2007;Pavelescu and Naeije, 2012). This was confirmed by a more recent magnetic resonance imaging study showing unchanged RV volumes after 35 min of hypoxic breathing in healthy volunteers (Jaijee et al, 2018). However there has been a report of increased RVEDA during hypoxic breathing in healthy volunteers (Netzer et al, 2017).…”

“…In the present study, the increase in PAP or PVR caused by hypoxic breathing was mild and below cutoff values for diagnosis of PH. This was confirmed by a more recent magnetic resonance imaging study showing unchanged RV volumes after 35 min of hypoxic breathing in healthy volunteers (Jaijee et al, 2018). A re-analysis of the results after exclusion of the three subjects with a QRS >100 ms did not affect the conclusions of the study.…”

Exercise cardiovascular magnetic resonance: development, current utility and future applications

“…The technique allowed aortic and pulmonary flow acquisition at numerous exercise levels and to 'true' submaximal intensity (> 85% age predicted maximum heart rate ), having being used to assess healthy subjects and patients with surgically repaired ventricular septal defects (VSD) [55,61]. Recently, ungated real time biventricular volume and aortic and pulmonary flows were performed during exercise to moderate exercise intensity in healthy subjects and patients with pulmonary arterial hypertension, the flow volumes acquired were similar to stroke volumes acquired from biventricular volumes [100].…”

The Future of Imaging in Pulmonary Hypertension: Better Assessment of Structure, Function, and Flow

“…Using RVEF as a surrogate of RV contractile reserve, Jaijee et al showed a decrease in RVEF with submaximal exercise in chronic PAH patients despite normal RV function at rest. 40 A separate study confirmed these findings and also showed that RV-PA coupling, as measured by stroke volume/end-systolic volume, was equally impaired with exercise in a small sample of patients with severe PAH. 41 In both studies, the key driver of poor RV contractility in patients with PAH was the inability to augment RV end-systolic volume during exercise.…”