Quantitative Perfusion
Sam Straw, MB
Clinical Research Fellow
University of Leeds, United Kingdom
Sam Straw, MB
Clinical Research Fellow
University of Leeds, United Kingdom
Charlotte Cole, MSc
Doctoral Fellow
Leeds Teaching Hospitals NHS Trust, United Kingdom
Maria Paton, PhD
Post doctoral research fellow
University of Leeds, United Kingdom
Henry Procter, MD
Research Fellow
University of Leeds, United Kingdom
Nicholas Jex, MD
PhD Fellow
Leeds Institute of Cardiovascular and Metabolic Medicine, England, United Kingdom
Hui Xue, PhD
Director, Imaging AI Program
National Institutes of Health
Bethesda, Maryland, United States
Amrit Chowdhary, MD
Cardiology
University of Leeds
WAKEFIELD, England, United Kingdom
Peter Kellman, PhD
Senior Scientist
National Institutes of Health, Maryland, United States
Marilena Giannoudi, MD
Research Fellow
University of Leeds, United Kingdom
Sharmaine Thirunavukarasu, MbCHB
Cardiology
University of Leeds
WILMSLOW, England, United Kingdom
John P. Greenwood, PhD
Professor
University of Leeds
Leeds, England, United Kingdom
Sven Plein, MD, PhD
Professor
University of Leeds
Leeds, England, United Kingdom
John Gierula, PhD
Post doctoral research fellow
University of Leeds
Leeds, England, United Kingdom
Klaus Witte, MD
Chair of device therapy
RWTH Aachen University
Leeds, England, Germany
Eylem Levelt, PhD
Associate Professor and Honorary Consultant
University of Leeds
Leeds, England, United Kingdom
The force-frequency relationship (FFR) is an intrinsic regulatory mechanism in which left ventricular contractility increases with rising heart rate to compensate for reduced diastolic filling time. Both left ventricular contractility and the point at which peak contractility occurs (the ‘critical’ heart rate) are attenuated in patients with heart failure with reduced ejection fraction (HFrEF).1 ‘Personalised’ rate-adaptive programming (upper sensor rate=critical heart rate) of cardiac implantable electronic devices (CIED) improves exercise time and preserves left ventricular function compared to conventional programming (upper sensor rate=220-age).2 We hypothesised that these effects might be driven by reductions in myocardial blood flow (MBF) when the critical heart rate is exceeded by conventional programming.
Methods:
We developed a novel, non-invasive assessment of the FFR and its relationship to global MBF in patients with CIED measured by 3.0 Tesla cardiac magnetic resonance (CMR) imaging (Prisma, Siemens, Erlangen, Germany). We first determined the FFR non-invasively by transthoracic echocardiography as previously described,1 comparing patients with HFrEF (22) with controls who had normal cardiac function (5). During image acquisition, CIED were programmed to increase heart rate at 15bpm increments from 50 (or resting heart rate) to 140bpm. The CMR protocol consisted of cine and perfusion imaging (motion corrected, automated in-line perfusion mapping) during which heart rate was programmed to 15bpm below, at, and 15bpm above the critical heart rate, defined as the heart rate at which peak systolic blood pressure/left-ventricular end-systolic volume index (cardiac contractility index) occurred. The assessment of left ventricular volumes, myocardial perfusion image reconstruction and processing was implemented using the Gadgetron software framework to determine global MBF.3
Results:
The clinical characteristics of patients and controls are displayed in the Table. The relationship between left ventricular ejection fraction, cardiac contractility index, cardiac index and heart rate were lower in patients with HFrEF compared to controls (Figure). The median critical heart rate in patients with heart failure was 95bpm (range 60-110bpm). MBF was not different below (mean difference 0.0029±0.22 ml/min/g; p=0.95) or above the critical heart (mean difference 0.017±0.19 ml/min/g;p=0.67).
Conclusion:
Around a third of patients with HFrEF will receive a CIED in their lifetime and personalised rate-adaptive programming improves exercise time and left ventricular function.2 In the present study, we show that MBF is not adversely affected by exceeding the critical heart rate, suggesting myocardial perfusion is unlikely to be a mechanism underpinning these effects. We also demonstrate that CMR with assessment of global MBF could safely be utilised in patients with CIED, which allowed these complex physiological experiments to be conducted.