Feasibility of cardiovascular magnetic resonance to detect oxygenation deficits in patients with multi-vessel coronary artery disease triggered by breathing maneuvers

Research Open Access Feasibility of cardiovascular magnetic resonance to detect oxygenation deficits in patients with multi-vessel coronary artery disease triggered by breathing maneuvers Kady Fischer1, 2, 3, Kyohei Yamaji4, Silvia Luescher1, Yasushi Ueki4, Bernd Jung3, Hendrik von Tengg-Kobligk3, Stephan Windecker4, Matthias G. Friedrich2, 5, Balthasar Eberle1 and Dominik P. Guensch1, 3Email author Journal of Cardiovascular Magnetic Resonance201820:31 https://doi.org/10.1186/s12968-018-0446-y ©  The Author(s). 2018 Received: 6 December 2017Accepted: 20 March 2018Published: 7 May 2018 Abstract Background Hyperventilation with a subsequent breath-hold has been successfully used as a non-pharmacological vasoactive stimulus to induce changes in myocardial oxygenation. The purpose of this pilot study was to assess if this maneuver is feasible in patients with multi-vessel coronary artery disease (CAD), and if it is effective at detecting coronary artery stenosis > 50% determined by quantitative coronary angiography (QCA). Methods Twenty-six patients with coronary artery stenosis (QCA > 50% diameter stenosis) underwent a contrast-free cardiovascular magnetic resonance (CMR) exam in the time interval between their primary coronary angiography and a subsequent percutaneous coronary intervention (PCI, n = 24) or coronary artery bypass (CABG, n = 2) revascularization procedure. The CMR exam involved standard function imaging, myocardial strain analysis, T2 mapping, native T1 mapping and oxygenation-sensitive CMR (OS-CMR) imaging. During OS-CMR, participants performed a paced hyperventilation for 60s followed by a breath-hold to induce a vasoactive stimulus. Ten healthy subjects underwent the CMR protocol as the control group. Results All CAD patients completed the breathing maneuvers with an average breath-hold duration of 48 ± 23 s following hyperventilation and without any complications or adverse effects. In comparison to healthy subjects, CAD patients had a significantly attenuated global myocardial oxygenation response to both hyperventilation (− 9.6 ± 6.8% vs. -3.1 ± 6.5%, p = 0.012) and apnea (11.3 ± 6.1% vs. 2.1 ± 4.4%, p < 0.001). The breath-hold maneuver unmasked regional oxygenation differences in territories subtended by a stenotic coronary artery in comparison to remote territory within the same patient (0.5 ± 3.8 vs. 3.8 ± 5.3%, p = 0.011). Conclusion Breathing maneuvers in conjunction with OS-CMR are clinically feasible in CAD patients. Furthermore, OS-CMR demonstrates myocardial oxygenation abnormalities in regional myocardium related to CAD without the use of pharmacologic vasodilators or contrast agents. A larger trial appears warranted for a better understanding of its diagnostic utility. Trial registration Clinical Trials Identifier: NCT02233634, registered 8 September 2014. Keywords Coronary artery diseaseOxygenation-sensitive cardiovascular magnetic resonanceBOLDBreathing maneuversHypocapniaHypercapnia Background In developed countries, more than 40% of deaths are due to cardiovascular diseases, in particular coronary artery disease (CAD) [1]. As a result, a large number of diagnostic procedures are performed for identifying or ruling out significant coronary artery stenosis. Some methods include identification of anatomically or hemodynamically significant stenosis in coronary arteries, although angiography based methods involve invasive measures, while others may assess perfusion deficits, indicating reduced blood flow. Many current invasive and non-invasive diagnostic techniques use surrogate markers for ischemia, however few of these common modalities fail to directly assess tissue ischemia itself, which reflects the imbalance of oxygen supply and demand. For other techniques that can assess ischemia, such as nuclear tests, these may involve exposure to radiation. Cardiovascular magnetic resonance imaging (CMR) avoids these drawbacks, although some sequences require the use of gadolinium based contrast agents, and thus are not suitable for patients with renal failure or with known contrast media allergy [2]. Oxygenation-sensitive (OS)-CMR has been introduced to directly assess myocardial oxygenation [3, 4]. This approach does not rely on pharmacological contrast agents, radiation, or invasive measures, but is based on the signal attenuating effects of the deoxyhemoglobin (dHb) fraction in the post-capillary venules, first described in the brain [5]. Hemoglobin (Hb) has paramagnetic properties when deoxygenated, which influences the phase evolution of water protons in the tissue leading to a loss in magnetic field homogeneity. This accelerates the relaxation of the spins, causing a CMR signal decrease. Oxygenated Hb has diamagnetic properties with a small stabilizing effect on the surrounding water proton relaxation times [5]. A variety of OS sequences exist, which primarily exploit this dephasing of the CMR signal relying on T2* effects. In this study we use a modified balanced steady state free procession (bSSFP) sequence that also incorporates T2/T1 effects. In healthy vasculature, vasoactive stimuli increase blood supply without an accompanying increase in oxygen demand (luxury perfusion) reducing the local dHb fraction, and thus an increase in myocardial oxygenation can be observed [6, 7]. In the presence of coronary stenosis or microvascular dysfunction, the vasodilatory response however is not as effective, or downstream vasculature is already in a compensatory state of maximum dilation. Consequently, myocardial oxygenation will not increase to the same extent as in myocardium perfused by a non-stenotic vessel. In very severe disease, a decrease may be recorded due to an inter-coronary steal, increased oxygen demand without a compensatory increase in blood flow, or post-stenotic capillary recruitment, i.e., when vessels down-stream of a stenosis dilate with deoxygenated blood [8]. In combination with pharmacological vasodilators, OS-CMR has been successfully used to detect myocardial oxygenation abnormalities in CAD [9–11]. Recently, we have investigated the use of breathing maneuvers as an endogenous non-pharmacologic, less expensive and potentially safer vasomotor stimulus. Hyperventilation induces myocardial and cerebral vasoconstriction [12, 13] in healthy subjects, and breath-holds can have a significantly stronger vasodilatory impact on myocardial oxygenation than the gold-standard of adenosine [14]. In an animal model, breathing maneuvers combined with OS-CMR identified myocardial oxygenation deficits in the presence of an acute coronary artery stenosis [15]. The combined breathing maneuver has several advantages for a clinical application. The associated hypocapnia not only allows for a longer breath-hold immediately thereafter [16], but also for monitoring a greater range of vasoreactivity, going from vasoconstriction to vasodilation during apnea. So far, the feasibility of such breathi (...truncated)