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ORAL PRESENTATION Open Access Differential responses of post-exercise recovery leg blood flow and oxygen uptake kinetics in HFPEF versus HFREF Richard B Thompson 1* , Joseph J Pagano 1 , Ian Paterson 3 , Jason Dyck 4 , Dalane Kitzman 5 , Mark Haykowsky 2 From 19th Annual SCMR Scientific Sessions Los Angeles, CA, USA. 27-30 January 2016 Background Delayed oxygen uptake (VO 2 ) kinetics during recovery from a bout of endurance exercise have been shown to be an important prognostic marker of all-cause mortal- ity in chronic heart failure (HF), where skeletal muscle is the predominant O 2 consumer. Few studies have examined skeletal muscle O 2 delivery/utilization, and no previous study has evaluated the differences between HF patients with reduced LVEF (HFREF) versus those with preserved LVEF (HFPEF). We used novel MRI-based techniques to non-invasively measure quadriceps (leg) blood flow, O 2 extraction and VO 2 recovery kinetics in clinically stable patients diagnosed with HFREF or HFPEF. Methods Leg flow and venous O 2 saturation (%SaO 2 ) were mea- sured in the femoral vein post-exercise (knee-extension) using MRI (Fig. 1A, B) as previously described (Magn Reson Med. 2014 Dec 22. doi: 10.1002/mrm.25564). These values in conjunction with arterial oxygen saturation (% SaO 2 , pulse oximeter), hemoglobin (Hgb) and hematocrit (from blood sampled prior to exercise) are used to calcu- late leg VO 2 , from the Fick equation (Fig. 1B). All subjects performed 4 min. of single-leg knee-extension exercise at 85% of their pre-determined peak power output. Leg blood flow, oxygen extraction and VO 2 were measured continuously during recovery for 3 minutes, starting within 1 second of exercise cessation. Recovery kinetics were quantified as the mean response time (MRT - defined in Fig. 1E, lower right panel) for all parameters, with comparison to healthy younger male controls (HC) from a previous study using the same methodology. Results HFPEF (n = 5, LVEF = 36 ± 11%, 69 ± 9 yrs) and HFPEF (n = 5, LVEF = 57 ± 6%, 67 ± 11 yrs) patients were recruited from the Alberta HEART study. Quadri- ceps muscle mass, peak leg flow, A-VO 2 difference and VO 2 were not significantly different between HFPEF and HFREF (p > 0.05 for all). However, HFREF patients had severe impairment of VO 2 recovery kinetics (increased MRT) , while HFPEF had a moderate impairment, as compared to HC (p < 0.05 for all comparison, Fig. 1E, bottom right). This is understood by considering the underlying flow and oxygen extraction kinetics. From Fig. 1D) both HF groups showed similarly impaired A-VO 2 recovery kinetics compared to controls (p < 0.05), however, the HFREF group had marked impair- ment in leg blood flow recovery dynamics, compared to both HFPEF and control groups (p < 0.05 for both com- parisons, Fig. 1C). Thus, it is the impaired recovery of flow in HFREF group which distinguishes the HFREF and HFPEF groups. Conclusions Whole body VO 2 recovery kinetics are related to the degree of functional impairment and are strongly pre- dictive of mortality. We show for the first time that muscle-specific VO 2 recovery kinetics are significantly more delayed in HFREF compared to HFPEF (reflecting a larger oxygen debt for a similar amount of work). These findings suggest distinct mechanisms may under- lie the reduced exercise capacity in HFREF vs HFPEF, with potentially distinct diagnostic metrics and thera- peutic approaches. 1 Biomedical Engineering, University of Alberta, Edmonton, AB, Canada Full list of author information is available at the end of the article Thompson et al. Journal of Cardiovascular Magnetic Resonance 2016, 18(Suppl 1):O9 http://www.jcmr-online.com/content/18/S1/O9 © 2016 Thompson et al. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/ publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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Page 1: ORAL PRESENTATION Open Access Differential responses of … · 2016. 5. 25. · ORAL PRESENTATION Open Access Differential responses of post-exercise recovery leg blood flow and oxygen

ORAL PRESENTATION Open Access

Differential responses of post-exercise recoveryleg blood flow and oxygen uptake kinetics inHFPEF versus HFREFRichard B Thompson1*, Joseph J Pagano1, Ian Paterson3, Jason Dyck4, Dalane Kitzman5, Mark Haykowsky2

From 19th Annual SCMR Scientific SessionsLos Angeles, CA, USA. 27-30 January 2016

BackgroundDelayed oxygen uptake (VO2) kinetics during recoveryfrom a bout of endurance exercise have been shown tobe an important prognostic marker of all-cause mortal-ity in chronic heart failure (HF), where skeletal muscleis the predominant O2 consumer. Few studies haveexamined skeletal muscle O2 delivery/utilization, and noprevious study has evaluated the differences between HFpatients with reduced LVEF (HFREF) versus those withpreserved LVEF (HFPEF). We used novel MRI-basedtechniques to non-invasively measure quadriceps (leg)blood flow, O2 extraction and VO2 recovery kinetics inclinically stable patients diagnosed with HFREF orHFPEF.

MethodsLeg flow and venous O2 saturation (%SaO2) were mea-sured in the femoral vein post-exercise (knee-extension)using MRI (Fig. 1A, B) as previously described (MagnReson Med. 2014 Dec 22. doi: 10.1002/mrm.25564). Thesevalues in conjunction with arterial oxygen saturation (%SaO2, pulse oximeter), hemoglobin (Hgb) and hematocrit(from blood sampled prior to exercise) are used to calcu-late leg VO2, from the Fick equation (Fig. 1B). All subjectsperformed 4 min. of single-leg knee-extension exercise at85% of their pre-determined peak power output. Legblood flow, oxygen extraction and VO2 were measuredcontinuously during recovery for 3 minutes, startingwithin 1 second of exercise cessation. Recovery kineticswere quantified as the mean response time (MRT -defined in Fig. 1E, lower right panel) for all parameters,

with comparison to healthy younger male controls (HC)from a previous study using the same methodology.

ResultsHFPEF (n = 5, LVEF = 36 ± 11%, 69 ± 9 yrs) andHFPEF (n = 5, LVEF = 57 ± 6%, 67 ± 11 yrs) patientswere recruited from the Alberta HEART study. Quadri-ceps muscle mass, peak leg flow, A-VO2 difference andVO2 were not significantly different between HFPEF andHFREF (p > 0.05 for all). However, HFREF patients hadsevere impairment of VO2 recovery kinetics (increasedMRT), while HFPEF had a moderate impairment, ascompared to HC (p < 0.05 for all comparison, Fig. 1E,bottom right). This is understood by considering theunderlying flow and oxygen extraction kinetics. FromFig. 1D) both HF groups showed similarly impairedA-VO2 recovery kinetics compared to controls (p <0.05), however, the HFREF group had marked impair-ment in leg blood flow recovery dynamics, compared toboth HFPEF and control groups (p < 0.05 for both com-parisons, Fig. 1C). Thus, it is the impaired recovery offlow in HFREF group which distinguishes the HFREFand HFPEF groups.

ConclusionsWhole body VO2 recovery kinetics are related to thedegree of functional impairment and are strongly pre-dictive of mortality. We show for the first time thatmuscle-specific VO2 recovery kinetics are significantlymore delayed in HFREF compared to HFPEF (reflectinga larger oxygen debt for a similar amount of work).These findings suggest distinct mechanisms may under-lie the reduced exercise capacity in HFREF vs HFPEF,with potentially distinct diagnostic metrics and thera-peutic approaches.

1Biomedical Engineering, University of Alberta, Edmonton, AB, CanadaFull list of author information is available at the end of the article

Thompson et al. Journal of Cardiovascular MagneticResonance 2016, 18(Suppl 1):O9http://www.jcmr-online.com/content/18/S1/O9

© 2016 Thompson et al. This is an Open Access article distributed under the terms of the Creative Commons Attribution License(http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, providedthe original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Page 2: ORAL PRESENTATION Open Access Differential responses of … · 2016. 5. 25. · ORAL PRESENTATION Open Access Differential responses of post-exercise recovery leg blood flow and oxygen

Figure 1 A) Anatomic image from a patient showing femoral vein location used for evaluation of flow and venous O2 saturation. B) O2saturation images from a patient at two time points (2 sec. and 60 sec.) following exercise, and the Fick equation for calculation of VO2. C) toE) show the average recovery curves for flow, venous O2 saturation and calculated leg VO2, for HFPEF (black), HFPEF (red) and healthy controls(HC, blue). MRT = mean response time, which is the sum of the delay term (Δ), to the onset of exponential recovery, and time constant of thebest-fit mono-exponential decay function (t), as shown in E). HFPEF = heart failure with preserved ejection fraction, HFREF = heart failure withreduced ejection fraction, Hgb = hemoglobin concentration.

Thompson et al. Journal of Cardiovascular MagneticResonance 2016, 18(Suppl 1):O9http://www.jcmr-online.com/content/18/S1/O9

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Page 3: ORAL PRESENTATION Open Access Differential responses of … · 2016. 5. 25. · ORAL PRESENTATION Open Access Differential responses of post-exercise recovery leg blood flow and oxygen

Authors’ details1Biomedical Engineering, University of Alberta, Edmonton, AB, Canada.2College of Nursing and Health Innovation, University of Texas at Arlington,Arlington, TX, USA. 3Medicine, University of Alberta, Edmonton, AB, Canada.4Pediatrics, University of Alberta, Edmonton, AB, Canada. 5Cardiology andGeriatrics, Wake Forest University, Wake Forest, NC, USA.

Published: 27 January 2016

doi:10.1186/1532-429X-18-S1-O9Cite this article as: Thompson et al.: Differential responses of post-exercise recovery leg blood flow and oxygen uptake kinetics in HFPEFversus HFREF. Journal of Cardiovascular Magnetic Resonance 2016 18(Suppl1):O9.

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Thompson et al. Journal of Cardiovascular MagneticResonance 2016, 18(Suppl 1):O9http://www.jcmr-online.com/content/18/S1/O9

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