Dynamic Handgrip Exercise: Feasibility and Physiologic Stress Response of a Potential Needle-Free Cardiac Magnetic Resonance Stress Test

Abstract

Background: Cardiac magnetic resonance (CMR) pharmacological stress-testing is a well-established technique for detecting myocardial ischemia. Although stressors and contrast agents seem relatively safe, contraindications and side effects must be considered. Substantial costs are further limiting its applicability. Dynamic handgrip exercise (DHE) may have the potential to address these shortcomings as a physiological stressor. We therefore evaluated the feasibility and physiologic stress response of DHE in relation to pharmacological dobutamine-stimulation within the context of CMR examinations. Methods: Two groups were prospectively enrolled: (I) volunteers without relevant disease and (II) patients with known CAD referred for stress-testing. A both-handed, metronome-guided DHE was performed over 2 min continuously with 80 contractions/minute by all participants, whereas dobutamine stress-testing was only performed in group (II). Short axis strain by fast-Strain-ENCoded imaging was acquired at rest, immediately after DHE and during dobutamine infusion. Results: Eighty middle-aged individuals (age 56 ± 17 years, 48 men) were enrolled. DHE triggered significant positive chronotropic (HR_rest: 68 ± 10 bpm, HR_DHE: 91 ± 13 bpm, p < 0.001) and inotropic stress response (GLS_rest: -19.4 ± 1.9%, GLS_DHE: -20.6 ± 2.1%, p < 0.001). Exercise-induced increase of longitudinal strain was present in healthy volunteers and patients with CAD to the same extent, but in general more pronounced in the midventricular and apical layers (p < 0.01). DHE was aborted by a minor portion (7%) due to peripheral fatigue. The inotropic effect of DHE appears to be non-inferior to intermediate dobutamine-stimulation (GLS_DHE= -19.5 ± 2.3%, GLS_Dob= -19.1 ± 3.1%, p = n.s.), whereas its chronotropic effect was superior (HR_DHE= 89 ± 14 bpm, HR_Dob= 78 ± 15 bpm, p < 0.001). Conclusions: DHE causes positive ino- and chronotropic effects superior to intermediate dobutamine-stimulation, suggesting a relevant increase of myocardial oxygen demand. DHE appears to be safe and timesaving with broad applicability. The data encourages further studies to determine its potential to detect obstructive CAD.

Keywords: CMR; fSENC; handgrip; longitudinal strain; stress-test.

Figure 1

(A) CMR protocol of the DHE study. Additional fSENC-sequences were acquired at rest, after 2 min of DHE, and (in the group of patients with CAD) during intermediate (20 μg/kg body weight/minute) and peak dobutamine/atropine stress (40 μg/kg body weight/minute + atropine). DHE was performed after all standard sequences at rest and before the start of pharmacological stress. (B) Illustration of DHE. Both-sided, metronome-guided rhythmic hand contractions were performed for 2 min at a frequency of 80/min. Handgrip rubber rings at about 50% of maximal voluntary contraction (MVC) were used. CMR, cardiac magnetic resonance imaging; fSENC, fast strain-encoded magnetic resonance imaging; DHE, dynamic handgrip exercise; CAD, coronary artery disease; MVC, maximal voluntary contraction.

Figure 2

Example of the image acquisition and GLS response of a healthy volunteer as visualized in the MyoStrain® software. (A) Cine sequence of a midventricular short axis slice. (B) fSENC-images of midventricular short axis slice at end-diastole. (C–E) Corresponding color-coded images after post-processing at end-diastole (C), end-systole at rest (D), and after 2 min of DHE (E). As demonstrated in (D,E), peak systolic longitudinal strain increased after DHE (color scale represents regional longitudinal strain). GLS, global longitudinal strain; fSENC, fast strain-encoded magnetic resonance imaging; DHE, dynamic handgrip exercise.

Figure 3

Example of the HR response during DHE of a 29-year-old, male subject. HR increased steadily as DHE progressed. After the end of DHE (120 s), HR fell rapidly toward the resting HR within 10 s. DHE, dynamic handgrip exercise; HR, heart rate.

Figure 4

(A) Individual response of HR after DHE in healthy individuals (left) and patients with CAD (right). All individuals showed an increase of HR after DHE. Mean HR of all individuals increased from 68 ± 10 bpm at rest to 91 ± 13 bpm after DHE (p < 0.001). (B) Individual response of GLS after DHE in healthy individuals (left) and patients with CAD (right). In 70% of our study population, GLS significantly increased (ΔGLS < −0.5%), in 25% it remained unchanged (ΔGLS ≥ −0.5% and ≤ 0.5%) and decreased (ΔGLS > 0.5%) in 5% of patients. Mean GLS increased from −19.4 ± 1.9% at rest to −20.6 ± 2.1% after DHE (p < 0.001). HR, heart rate; LS, longitudinal strain; GLS, global longitudinal strain; DHE, dynamic handgrip exercise; CAD, coronary artery disease.

Figure 5

Response of segmental ΔLS after DHE visualized in the AHA 16-Segment model bullseye. LS significantly increased in every midventricular and apical segment. Yellow, ΔLS > 0.0%; bright green, ΔLS 0.0 to –0.9%; green, ΔLS –1.0 to –1.9%; dark green, ΔLS ≤ –2.0%. LS, longitudinal strain; DHE, dynamic handgrip exercise; AHA, American Heart Association.

Figure 6

ROC-curve analyses for the differentiation between healthy individuals and patients with CAD. (A) GLS_DHE: cut-off value > –20.6%. AUC = 0.744, p < 0.001, sensitivity 76.7%, specificity 68.0%. (B) ΔGLS_DHE (absolute difference between GLS at rest and after DHE): cut-off value >–1.7%. AUC = 0.662, p = 0.009, sensitivity 80.0%, specificity 48.0%. ROC, receiver operating characteristic; CAD, coronary artery disease; GLS, global longitudinal strain; AUC, area under the curve; DHE, dynamic handgrip exercise.

Figure 7

(A) Heart response in group II after DHE (green) and during dobutamine stress (red). After 2 min of DHE, HR significantly increased. HR_DHE was significantly higher compared with HR during intermediate dobutamine stress. (B) GLS response in group II after DHE (green) and during dobutamine stress (red). GLS significantly increased after DHE. During dobutamine stress, GLS increased at intermediate stress level, before it decreased at maximum dobutamine/atropine stress. Error bars represent the standard error of the mean. HR, heart rate; DHE, dynamic handgrip exercise; GLS, global longitudinal strain.

Figure 8

Color-coded fSENC images visualizing longitudinal strain at rest (A) and after DHE (B) of an excluded patient with a positive dobutamine stress test. Invasive coronary angiography revealed a significant stenosis of the right coronary artery (C) (color scale represents regional longitudinal strain). fSENC, fast strain-encoded magnetic resonance imaging; DHE, dynamic handgrip exercise.