scholarly journals Heart failure with preserved ejection fraction: chronic low-intensity interval exercise training preserves myocardial O2 balance and diastolic function

2013 ◽  
Vol 114 (1) ◽  
pp. 131-147 ◽  
Author(s):  
Kurt D. Marshall ◽  
Brittany N. Muller ◽  
Maike Krenz ◽  
Laurin M. Hanft ◽  
Kerry S. McDonald ◽  
...  

We have previously reported chronic low-intensity interval exercise training attenuates fibrosis, impaired cardiac mitochondrial function, and coronary vascular dysfunction in miniature swine with left ventricular (LV) hypertrophy (Emter CA, Baines CP. Am J Physiol Heart Circ Physiol 299: H1348–H1356, 2010; Emter CA, et al. Am J Physiol Heart Circ Physiol 301: H1687–H1694, 2011). The purpose of this study was to test two hypotheses: 1) chronic low-intensity interval training preserves normal myocardial oxygen supply/demand balance; and 2) training-dependent attenuation of LV fibrotic remodeling improves diastolic function in aortic-banded sedentary, exercise-trained (HF-TR), and control sedentary male Yucatan miniature swine displaying symptoms of heart failure with preserved ejection fraction. Pressure-volume loops, coronary blood flow, and two-dimensional speckle tracking ultrasound were utilized in vivo under conditions of increasing peripheral mean arterial pressure and β-adrenergic stimulation 6 mo postsurgery to evaluate cardiac function. Normal diastolic function in HF-TR animals was characterized by prevention of increased time constant of isovolumic relaxation, normal LV untwisting rate, and enhanced apical circumferential and radial strain rate. Reduced fibrosis, normal matrix metalloproteinase-2 and tissue inhibitors of metalloproteinase-4 mRNA expression, and increased collagen III isoform mRNA levels ( P < 0.05) accompanied improved diastolic function following chronic training. Exercise-dependent improvements in coronary blood flow for a given myocardial oxygen consumption ( P < 0.05) and cardiac efficiency (stroke work to myocardial oxygen consumption, P < 0.05) were associated with preserved contractile reserve. LV hypertrophy in HF-TR animals was associated with increased activation of Akt and preservation of activated JNK/SAPK. In conclusion, chronic low-intensity interval exercise training attenuates diastolic impairment by promoting compliant extracellular matrix fibrotic components and preserving extracellular matrix regulatory mechanisms, preserves myocardial oxygen balance, and promotes a physiological molecular hypertrophic signaling phenotype in a large animal model resembling heart failure with preserved ejection fraction.

2018 ◽  
Vol 125 (1) ◽  
pp. 86-96 ◽  
Author(s):  
T. Dylan Olver ◽  
Jenna C. Edwards ◽  
Brian S. Ferguson ◽  
Jessica A. Hiemstra ◽  
Pamela K. Thorne ◽  
...  

Conventional treatments have failed to improve the prognosis of heart failure with preserved ejection fraction (HFpEF) patients. Thus, the purpose of this study was to determine the therapeutic efficacy of chronic interval exercise training (IT) on large-conductance Ca2+-activated K+ (BKCa) channel-mediated coronary vascular function in heart failure. We hypothesized that chronic interval exercise training would attenuate pressure overload-induced impairments to coronary BKCa channel-mediated function. A translational large-animal model with cardiac features of HFpEF was used to test this hypothesis. Specifically, male Yucatan miniswine were divided into three groups ( n = 7/group): control (CON), aortic banded (AB)-heart failure (HF), and AB-interval trained (HF-IT). Coronary blood flow, vascular conductance, and vasodilatory capacity were measured after administration of the BKCa channel agonist NS-1619 both in vivo and in vitro in the left anterior descending coronary artery and isolated coronary arterioles, respectively. Skeletal muscle citrate synthase activity was decreased and left ventricular brain natriuretic peptide levels increased in HF vs. CON and HF-IT animals. A parallel decrease in NS-1619-dependent coronary vasodilatory reserve in vivo and isolated coronary arteriole vasodilatory responsiveness in vitro were observed in HF animals compared with CON, which was prevented in the HF-IT group. Although exercise training prevented BKCa channel-mediated coronary vascular dysfunction, it did not change BKCa channel α-subunit mRNA, protein, or cellular location (i.e., membrane vs. cytoplasm). In conclusion, these results demonstrate the viability of chronic interval exercise training as a therapy for central and peripheral adaptations of experimental heart failure, including BKCa channel-mediated coronary vascular dysfunction. NEW & NOTEWORTHY Conventional treatments have failed to improve the prognosis of heart failure with preserved ejection fraction (HFpEF) patients. Our findings show that chronic interval exercise training can prevent BKCa channel-mediated coronary vascular dysfunction in a translational swine model of chronic pressure overload-induced heart failure with relevance to human HFpEF.


Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Gudrun Dieberg ◽  
Hashbullah Ismail ◽  
Francesco Giallauria ◽  
Neil A Smart

Background: Exercise training induces physical adaptations for heart failure patients with systolic dysfunction but less is known about those patients with preserved ejection fraction. Objectives: To establish if exercise training produces changes in peak VO 2 and related measures, quality of life, general health and diastolic function in heart failure patients with preserved ejection fraction (HFpEF). Methods: We conducted a MEDLINE search (1985 to March 2014), for exercise based rehabilitation trials in heart failure, using search terms ‘exercise training, heart failure with preserved ejection fraction, heart failure with normal ejection fraction, peak VO 2 and diastolic heart dysfunction’. Seven intervention studies were included providing a total of 144 exercising subjects and 114 control subjects, a total of 258 participants. Results: Peak VO 2 increased by a mean difference (MD) 2.13 ml.kg -1 .min -1 (95% C.I. 1.54 to 2.71, p<0.00001) in exercise training versus sedentary control, equating to a 17% improvement from baseline. The corresponding data for V E /VCO 2 slope MD 0.85 ml.kg -1 .min -1 (95% C.I. 0.05 to 1.65, p=0.04); maximum heart rate MD 5.60 bpm (95% C.I. 3.95 to 7.25, p<0.00001); and 6 Minute Walk Test (6MWT) MD 32.1m (95% C.I. 17.2 to 47.1, p<0.0001); diastolic function; E/A ratio MD 0.07 (95% C.I. 0.02 to 0.12, p=0.005); E/E’ ratio MD -2.31 (95% C.I. -3.44 to -1.19, p<0.0001); Deceleration time (D T ) MD -13.2 msec (95% C.I. -19.8 to -6.5, p=0.0001); Minnesota Living with Heart Failure Questionnaire (MLHFQ) MD -6.50 (95% C.I. -9.47 to -3.53, p<0.0001); Short Form (36) Health Survey MD 15.6 (95% C.I. 7.4 to 23.8, p=0.0002). In 3,744 hours patient-hours of training, not one death was directly attributable to exercise. Conclusions: Exercise training appears to effect several health-related improvements in people with heart failure and preserved ejection fraction.


2018 ◽  
Vol 124 (4) ◽  
pp. 1034-1044 ◽  
Author(s):  
Jessica A. Hiemstra ◽  
Adam B. Veteto ◽  
Michelle D. Lambert ◽  
T. Dylan Olver ◽  
Brian S. Ferguson ◽  
...  

Exercise improves clinical outcomes in patients diagnosed with heart failure with reduced ejection fraction (HFrEF), in part via beneficial effects on cardiomyocyte Ca2+ cycling during excitation-contraction coupling (ECC). However, limited data exist regarding the effects of exercise training on cardiomyocyte function in patients diagnosed with heart failure with preserved ejection fraction (HFpEF). The purpose of this study was to investigate cardiomyocyte Ca2+ handling and contractile function following chronic low-intensity exercise training in aortic-banded miniature swine and test the hypothesis that low-intensity exercise improves cardiomyocyte function in a large animal model of pressure overload. Animals were divided into control (CON), aortic-banded sedentary (AB), and aortic-banded low-intensity trained (AB-LIT) groups. Left ventricular cardiomyocytes were electrically stimulated (0.5 Hz) to assess Ca2+ homeostasis (fura-2-AM) and unloaded shortening during ECC under conditions of baseline pacing and pacing with adrenergic stimulation using dobutamine (1 μM). Cardiomyocytes in AB animals exhibited depressed Ca2+ transient amplitude and cardiomyocyte shortening vs. CON under both conditions. Exercise training attenuated AB-induced decreases in cardiomyocyte Ca2+ transient amplitude but did not prevent impaired shortening vs. CON. With dobutamine, AB-LIT exhibited both Ca2+ transient and shortening amplitude similar to CON. Adrenergic sensitivity, assessed as the time to maximum inotropic response following dobutamine treatment, was depressed in the AB group but normal in AB-LIT animals. Taken together, our data suggest exercise training is beneficial for cardiomyocyte function via the effects on Ca2+ homeostasis and adrenergic sensitivity in a large animal model of pressure overload-induced heart failure. NEW & NOTEWORTHY Conventional treatments have failed to improve the prognosis of heart failure with preserved ejection fraction (HFpEF) patients. Our findings show chronic low-intensity exercise training can prevent cardiomyocyte dysfunction and impaired adrenergic responsiveness in a translational large animal model of chronic pressure overload-induced heart failure with relevance to human HFpEF.


2015 ◽  
Vol 119 (6) ◽  
pp. 726-733 ◽  
Author(s):  
Gudrun Dieberg ◽  
Hashbullah Ismail ◽  
Francesco Giallauria ◽  
Neil A. Smart

Exercise training induces physical adaptations for heart failure patients with systolic dysfunction, but less is known about those patients with preserved ejection fraction. To establish whether exercise training produces changes in peak V̇o2 and related measures, quality of life, general health, and diastolic function in heart failure patients with preserved ejection fraction. We conducted a MEDLINE search (1985 to October 10, 2014), for exercise-based rehabilitation trials in heart failure, using search terms “exercise training, heart failure with preserved ejection fraction, heart failure with normal ejection fraction, peak V̇o2, and diastolic heart dysfunction”. Seven intervention studies were included providing a total of 144 exercising subjects and 114 control subjects, a total of 258 participants. Peak V̇o2 increased by a mean difference (MD) 2.13 ml·kg−1·min−1 [95% confidence interval (CI) 1.54 to 2.71, P < 0.00001] in exercise training vs. sedentary control, equating to a 17% improvement from baseline. The corresponding data are provided for the following exercise test variables: V̇e/V̇co2 slope, MD 0.85 ml·kg−1·min−1 (95% CI 0.05 to 1.65, P = 0.04); maximum heart rate, MD 5.60 beats per minute (95% CI 3.95 to 7.25, P < 0.00001); Six-Minute Walk Test, MD 32.1 m (95% CI 17.2 to 47.1, P < 0.0001); and indices of diastolic function: E/A ratio, MD 0.07 (95% CI 0.02 to 0.12, P = 0.005); E/E′ ratio MD −2.31 (95% CI −3.44 to −1.19, P < 0.0001); deceleration time (DT), MD −13.2 ms (95% CI −19.8 to −6.5, P = 0.0001); and quality of life: Minnesota Living with Heart Failure Questionnaire, MD −6.50 (95% CI −9.47 to −3.53, P < 0.0001); and short form-36 health survey (physical dimension), MD 15.6 (95% CI 7.4 to 23.8, P = 0.0002). In 3,744 h patient-hours of training, not one death was directly attributable to exercise. Exercise training appears to effect several health-related improvements in people with heart failure and preserved ejection fraction.


2016 ◽  
Vol 86 (1-2) ◽  
Author(s):  
Erick Chan ◽  
Francesco Giallauria ◽  
Carlo Vigorito ◽  
Neil A. Smart

<p>Exercise training induces physical adaptations for heart failure patients with systolic dysfunction but less is known about those patients with preserved ejection fraction. This study's aims were to establish if exercise training produces changes in peak VO<sub>2</sub> and related measures, quality of life, general health and diastolic function in heart failure patients with preserved ejection fraction (HFpEF). We conducted a MEDLINE search (1985 to September 1, 2015), for exercise based rehabilitation trials in heart failure, using search terms ‘exercise training, heart failure with preserved ejection fraction, heart failure with  normal ejection fraction, peak VO<sub>2</sub> and diastolic heart dysfunction’. Eight intervention studies were included providing a total of 174 exercising subjects and 143 control subjects, a total of 317 participants. Peak VO<sub>2</sub> increased by a mean difference (MD) 2.08 mL kg<sup>-1 </sup>min<sup>-1</sup> (95% C.I. 1.51 to 2.65, p&lt;0.00001) in exercise training versus sedentary control, equating to a 17% improvement from baseline. V<sub>E</sub>/VCO<sub>2</sub> slope was not different between groups, MD -3.10 mL kg<sup>-1 </sup>min<sup>-1</sup> (95% C.I. -7.47 to 1.27, p=0.16); maximum heart rate was significantly increased in exercise groups, MD 3.46 bpm (95% C.I. 2.41 to 4.51, p&lt;0.00001); 6 Minute Walk Distance (6MWT) MD 32.1m (95% C.I. 17.2 to 47.1, p&lt;0.0001); diastolic  function; the ratio of early to late filling (E/A ratio) was improved after exercise training MD 0.07 (95% C.I. 0.02 to 0.12, p=0.006); as was filling pressure E/E’ ratio MD -2.38 (95% C.I. -3.47 to -1.28, p&lt;0.0001); Deceleration time (D<sub>T</sub>) MD -13.2 msec (95% C.I. -19.8 to -6.5, p=0.0001); Minnesota Living with Heart Failure Questionnaire (MLHFQ) MD -6.77 (95% C.I. -9.70 to -3.84, p&lt;0.00001); Short Form (36) Health Survey MD 11.38 (95% C.I. 5.28 to 17.48, p=0.0003).  In 3222 patient-hours of training, not a single death was directly attributable to exercise. Exercise training appears to effect several health-related improvements in people with heart failure and preserved ejection fraction.</p>


2021 ◽  
Author(s):  
Chenchen Zhuang ◽  
Xufei Luo ◽  
Qiongying Wang ◽  
Shipeng Li ◽  
Xiaofang Zhang ◽  
...  

Abstract Background: We aimed to better understand the effects of two exercise training interventions [endurance training and a combination of endurance and resistance training (combined exercise)] and two physiotherapies [functional electrical stimulation (FES) and inspiratory muscle training (IMT)] on diastolic function, exercise performance and quality of life (QoL) in heart failure with preserved ejection fraction (HFpEF) patients.Methods: Cochrane Library, EMBASE and MEDLINE via PubMed for randomized controlled trials were searched from their inception to May 2020. The methodological quality was assessed using the Physiotherapy Evidence Database sacle. All analyses were used by STATA.Results: A total of 14 articles on 13 trials were included in this meta-analysis with 673 HFpEF patients. The pooling revealed that peak oxygen uptake was improved by endurance training [MD (95% CI): 1.89 ml.kg-1.min-1 (1.32, 2.46), P < 0.001], FES [MD (95% CI): 2.28 ml.kg-1.min-1 (0.92, 3.65), P = 0.001] and IMT [MD (95% CI): 2.72 ml.kg-1.min-1 (1.44, 3.99), P < 0.001]. Similar results were observed for 6-minute walk test and QoL. Besides, endurance training increased arterial venous oxygen difference [MD (95% CI): 1.41 (0.09, 2.74), P = 0.036]. Combined exercise was beneficial to the ratio of peak early to late diastolic mitral inflow velocities [MD (95% CI): -2.90 (-4.97, -0.83), P = 0.006] and the early diastolic mitral annual velocity [MD (95% CI): 1.40 (0.68, 2.12), P = 0.006]. IMT improved ventilation/carbon dioxide ratio slope [MD (95% CI): -3.36 ml.kg-1.min-1 (-6.17, -0.54), P = 0.019].Conclusions: FES and IMT may be therapeutic options to improve functional capacity and QoL in HFpEF patients, and the outcomes are similar to endurance training. Combined exercise tends to improve diastolic function in HFpEF patients.


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