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

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: BOLD; Breathing maneuvers; Coronary artery disease; Hypercapnia; Hypocapnia; Oxygenation-sensitive cardiovascular magnetic resonance.

Conflict of interest statement

Ethics approval and consent to participate

The study was approved by the cantonal ethics board of Bern (Swissethics-ID: PB_2016–02124) and complies with the Declaration of Helsinki. All subjects had given their informed consent prior to enrolment into the study.

Consent for publication

Not applicable.

Competing interests

KF, MF and DG hold an international patent (Patent Number: 9615754) and a second pending patent (US Patent Application No. 15/483,712) for the use of breathing maneuvers for diagnostics purpose. MF is board member, advisor, and shareholder of Circle Cardiovascular Imaging Inc., the manufacturer of the software used for CMR image evaluation.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1

Study Protocol. Patients were recruited between staged coronary interventions or the initial diagnostic angiography and surgical revascularization therapy. After primary angiography, QCA of all vessels was performed and patients were recruited if there was at least one untreated vessel with a significant lesion (diameter stenosis; DS > 50%). For oxygen sensitive cardiovascular magnetic resonance (OS-CMR), a rest image was obtained during a short breath-hold. Participants then hyperventilated for 60s (30 breaths per minute, paced by a metronome), controlled through qualitative capnography with visual confirmation of sufficient respiratory excursions. This was immediately followed by a long breath-hold, which was imaged throughout its entire duration with repetitive OS measurements (grey boxes). Quality control of apnea also included monitoring for absence of exhaled carbon dioxide with capnography and breathing motion artifacts in the images

Fig. 2

Myocardial oxygenation response throughout the breath-hold. Left panel, top row (a): In healthy subjects, myocardial oxygenation increases rapidly at the beginning of the breath-hold and is maintained throughout apnea, as shown in a healthy male as well as by the mean response of all healthy subjects (right panel, grey shaded graph). Left panel, middle row (b): OS images show a regional response (square) in a coronary artery disease (CAD) patient, whose myocardial oxygenation decreased in territory subtended to left anterior descending (LAD) stenosis (marked with a solid lined box) and in territory reperfused via a stented right coronary artery (RCA) (marked with dotted line), while the remote territory responded with an oxygenation increase (left circumflex (LCx); also note artifact rejection in a small infero-lateral region). Left panel, bottom row (c): This sequence represents a CAD patient (stented LAD, RCA stenosis) with global dysfunction in whom all territories revealed an oxygenation deficit (purple dots).

Fig. 3

Tissue characterization and ventricular strain. Mean ± SD are shown for T1 mapping, T2 mapping and peak circumferential strain for the global responses of healthy controls (Hea) and the patient group (CAD), along with the individual regional responses of the CAD patients for territories currently affected by a stenosis (Sten) > 50%DS, remote (Rem) and recently reperfused (Rep) territories. Three patients did not have a primary PCI procedure prior to the CMR exam (white markers). *p < 0.05 between groups for global analysis. †p < 0.05 for regional analysis of Sten or Rep vs. Rem

Fig. 4

Global and regional OS-CMR. Mean ± SD are shown for the global responses of healthy control subjects (Hea) and the CAD patient group (CAD). Individual data points demonstrate that during the breath-hold (BH), the majority of patients had a lower response in the post-stenotic (Sten) and reperfused (Rep) territories than remote (Rem). Three patients did not have a primary PCI procedure prior to the CMR exam (white markers). *p < 0.05 between groups for global analysis. †p < 0.05 for regional analysis of Sten or Rep vs. Rem

Fig. 5

Different patterns of myocardial oxygenation response and ischemia/reperfusion injury. A pictogram of the angiography results is shown for the RCA, LCx and LAD and their major branches (left to right), and collateralizations (red dotted lines). For the CMR images, the normal range (mean + SD) of the healthy subjects is shown in the colour legends below, with strain and OS-CMR shown at end-systole, and T1 and T2 imaged in diastole. Patients a and b underwent primary PCI during the first visit and have reperfused vascular territories in addition to a stenosis. Patients c-e were scheduled for a later PCI or CABG, thus their index angiography was only diagnostic and there is no revascularized territory at the time of the CMR scan. Solid line boxes highlight the post-stenotic and dotted lines the reperfused territories. Detailed information for each case is provided in the Additional file 2

Fig. 6

Myocardial oxygenation in truncated breath-holds. In this patient with a 51% RCA stenosis (solid line box) and reperfused LAD (dotted line marker), an extended breath-hold could not be performed. Yet, with the last image obtained only at 13 s, the RCA territory already shows an oxygen deficit in comparison to the increase of the remote territory