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 O2: 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-CO2 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.
Highlights
Pulmonary arterial hypertension (PAH) is a disease characterized by adverse remodeling of the peripheral pulmonary arteries leading to elevated pulmonary arterial pressure (PAP) and progressive right ventricular (RV) dysfunction [5, 17]
It is known that RV function is a strong predictor of mortality, outperforming pulmonary vascular resistance (PVR) [18, 33, 35], but there is currently no method to determine which RV phenotype is destined to fail despite medical therapy
We used real-time exercise imaging to determine the effect of elevated afterload on RV contractile reserve during normobaric hypoxia and in chronic PAH before the RV becomes dilated or impaired
Summary
Pulmonary arterial hypertension (PAH) is a disease characterized by adverse remodeling of the peripheral pulmonary arteries leading to elevated pulmonary arterial pressure (PAP) and progressive right ventricular (RV) dysfunction [5, 17]. In the early stages of PAH, the RV remains coupled to its afterload and maintains efficient energy transfer by a homeometric adaptive increase in wall thickness and contractility. With cumulative exposure to increasing afterload, heterometric adaptation occurs with progressive RV dilatation to preserve stroke volume (SV) until the more advanced stages of disease, when wall stress rises and ventriculoarterial uncoupling occurs with reduced cardiac output [26]. RV reserve can be assessed noninvasively during exercise using real-time imaging to provide a surrogate marker of stress-induced cardiopulmonary uncoupling [16, 21]. We used real-time exercise imaging to determine the effect of elevated afterload on RV contractile reserve during normobaric hypoxia (which has been associated with transient acute pulmonary hypertension) and in chronic PAH before the RV becomes dilated or impaired. We hypothesized that the RV has limited capacity to recruit contractile function when exposed to elevated afterload despite compensated function at rest
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