scholarly journals ­Heart Failure with Preserved Ejection Fraction Diminishes Peripheral Hemodynamics and Accelerates Exercise-Induced Neuromuscular Fatigue

Author(s):  
Joshua C. Weavil ◽  
Taylor S. Thurston ◽  
Thomas J. Hureau ◽  
Jayson R. Gifford ◽  
Philip Kithas ◽  
...  

This study investigated the impact of heart failure with a preserved ejection fraction (HFpEF) on neuromuscular fatigue and peripheral hemodynamics during small muscle mass exercise not limited by cardiac output. Eight HFpEF patients (ejection-fraction: 61±2%, NYHA II-III) and eight healthy-controls performed dynamic single-leg knee-extension exercise [80% peak workload] to task-failure and maximal intermittent isometric quadriceps contractions (8×15-s, 20-s rest). Controls repeated knee-extension at the same absolute workload as the HFpEF. During knee-extension, leg blood flow was quantified using Doppler ultrasound. Pre- to post-exercise changes in quadriceps twitch-torque (ΔQtw, peripheral fatigue), voluntary-activation (ΔVA, central fatigue), and corticospinal excitability were quantified. At the same relative intensity, HFpEF (24±5W) and controls (42±6W) had a similar time to task-failure (~10min), ΔQtw (~50%), and ΔVA (~6%) (P>0.3). This resulted in a greater exercise-induced change in neuromuscular function per unit work in HFpEF, which was significantly correlated with a slower leg blood flow response time (r=0.77). Knee-extension exercise at the same absolute workload resulted in a ~40% lower leg blood flow and greater ΔQtw (56±15 vs 11±10%) and ΔVA (5±3 vs 0±2%) in HFpEF than controls (P<0.05). Corticospinal excitability remained unaltered during exercise in both groups. Finally, despite a similar ΔVA, ΔQtw was larger in HFpEF compared to controls during isometric exercise (-49±9 vs -23±2%, P<0.05). In conclusion, HFpEF are characterized by a greater susceptibility to neuromuscular fatigue during exercise not limited by cardiac output. The patients' compromised peripheral hemodynamic response to exercise likely accounts, at least partly, for the attenuated fatigue resistance in this population.

Author(s):  
Michael A. Francisco ◽  
Joshua F. Lee ◽  
Zachary Barrett-O’Keefe ◽  
H. Jonathan Groot ◽  
Stephen M. Ratchford ◽  
...  

While there is emerging evidence of peripheral microvascular dysfunction in patients with heart failure with preserved ejection fraction (HFpEF) that may be related to systemic inflammation and redox imbalance, disease-related changes in locomotor muscle microvascular responsiveness have not been determined. This study combined passive leg movement and biomarker assessments of inflammation and oxidative damage to determine the magnitude and mechanisms of lower limb microvascular function in patients with HFpEF (71±1 years; n=44) compared with healthy, similarly aged controls (68±2 years; n=39). Leg blood flow, heart rate, mean arterial pressure, and stroke volume were assessed, and plasma biomarkers of inflammation and oxidative damage were also determined. A significantly attenuated passive leg movement–induced peak change in leg blood flow (263±25 versus 371±31 mL/min, HFpEF versus control) and leg vascular conductance (2.99±0.32 versus 3.88±0.34 mL/min per mm Hg, HFpEF versus control) was observed in patients compared with controls. Similarly, the total hyperemic response to passive leg movement, expressed as leg blood flow AUC and leg vascular conductance AUC , was ≈40% less in patients with HFpEF versus control. Significantly greater C-reactive protein, IL-6 (interleukin-6), and malondialdehyde were observed in patients with HFpEF but were not correlated with passive leg movement responses. These data provide new evidence of a decline in lower limb microvascular function within a milieu of vascular inflammation that may contribute to locomotor muscle dysfunction in patients with HFpEF.


2021 ◽  
Vol 24 (4) ◽  
pp. 304-314
Author(s):  
M. A. Manukyan ◽  
A. Y. Falkovskaya ◽  
V. F. Mordovin ◽  
T. R. Ryabova ◽  
I. V. Zyubanova ◽  
...  

BACKGROUND: It is expected that a steady increase in the incidence of diabetes and resistant hypertension (RHTN), along with an increase in life expectancy, will lead to a noticeable increase in the proportion of patients with heart failure with preserved ejection fraction (HFpEF). At the same time, data on the frequency of HFpEF in a selective group of patients with RHTN in combination with diabetes are still lacking, and the pathophysiological and molecular mechanisms of its formation have not been yet studied sufficiently.AIM: To assess the features of the development HFpEF in diabetic and non-diabetic patients with RHTN, as well as to determine the factors associated with HFpEF.MATERIALS AND METHODS: In the study were included 36 patients with RHTN and type 2 diabetes mellitus (DM) (mean age 61.4 ± 6.4 years, 14 men) and 33 patients with RHTN without diabetes, matched by sex, age and level of systolic blood pressure (BP). All patients underwent baseline office and 24-hour BP measurement, echocardiography with assess diastolic function, lab tests (basal glycemia, HbA1c, creatinine, aldosterone, TNF-alpha, hsCRP, brain naturetic peptide, metalloproteinases of types 2, 9 (MMP-2, MMP-9) and tissue inhibitor of MMP type 1 (TIMP-1)). HFpEF was diagnosed according to the 2019 AHA/ESC guidelines.RESULTS: The frequency of HFpEF was significantly higher in patients with RHTN with DM than those without DM (89% and 70%, respectively, p=0.045). This difference was due to a higher frequency of such major functional criterion of HFpEF as E/e’≥15 (p=0.042), as well as a tendency towards a higher frequency of an increase in left atrial volumes (p=0.081) and an increase in BNP (p=0.110). Despite the comparable frequency of diastolic dysfunction in patients with and without diabetes (100% and 97%, respectively), disturbance of the transmitral blood flow in patients with DM were more pronounced than in those without diabetes. Deterioration of transmitral blood flow and pseudo-normalization of diastolic function in diabetic patients with RHTN have relationship not only with signs of carbohydrate metabolism disturbance, but also with level of pulse blood pressure, TNF-alfa, TIMP-1 and TIMP-1 / MMP-2 ratio, which, along with the incidence of atherosclerosis, were higher in patients with DM than in those without diabetes.CONCLUSIONS: Thus, HFpEF occurs in the majority of diabetic patients with RHTN. The frequency of HFpEF in patients with DN is significantly higher than in patients without it, which is associated with more pronounced impairments of diastolic function. The progressive development of diastolic dysfunction in patients with diabetes mellitus is associated not only with metabolic disorders, but also with increased activity of chronic subclinical inflammation, profibrotic state and high severity of vascular changes.


2019 ◽  
Vol 316 (5) ◽  
pp. R512-R524 ◽  
Author(s):  
Zachary Barrett-O’Keefe ◽  
Joshua F. Lee ◽  
Stephen J. Ives ◽  
Joel D. Trinity ◽  
Melissa A. H. Witman ◽  
...  

Patients suffering from heart failure with reduced ejection fraction (HFrEF) experience impaired limb blood flow during exercise, which may be due to a disease-related increase in α-adrenergic receptor vasoconstriction. Thus, in eight patients with HFrEF (63 ± 4 yr) and eight well-matched controls (63 ± 2 yr), we examined changes in leg blood flow (Doppler ultrasound) during intra-arterial infusion of phenylephrine (PE; an α1-adrenergic receptor agonist) and phentolamine (Phen; a nonspecific α-adrenergic receptor antagonist) at rest and during dynamic single-leg knee-extensor exercise (0, 5, and 10 W). At rest, the PE-induced reduction in blood flow was significantly attenuated in patients with HFrEF (−15 ± 7%) compared with controls (−36 ± 5%). During exercise, the controls exhibited a blunted reduction in blood flow induced by PE (−12 ± 4, −10 ± 4, and −9 ± 2% at 0, 5, and 10 W, respectively) compared with rest, while the PE-induced change in blood flow was unchanged compared with rest in the HFrEF group (−8 ± 5, −10 ± 3, and −14 ± 3%, respectively). Phen administration increased leg blood flow to a greater extent in the HFrEF group at rest (+178 ± 34% vs. +114 ± 28%, HFrEF vs. control) and during exercise (36 ± 6, 37 ± 7, and 39 ± 6% vs. 13 ± 3, 14 ± 1, and 8 ± 3% at 0, 5, and 10 W, respectively, in HFrEF vs. control). Together, these findings imply that a HFrEF-related increase in α-adrenergic vasoconstriction restrains exercising skeletal muscle blood flow, potentially contributing to diminished exercise capacity in this population.


1997 ◽  
Vol 83 (6) ◽  
pp. 1933-1940 ◽  
Author(s):  
Chim C. Lang ◽  
Don B. Chomsky ◽  
Javed Butler ◽  
Shiv Kapoor ◽  
John R. Wilson

Lang, Chim C., Don B. Chomsky, Javed Butler, Shiv Kapoor, and John R. Wilson. Prostaglandin production contributes to exercise-induced vasodilation in heart failure. J. Appl. Physiol. 83(6): 1933–1940, 1997.—Endothelial release of prostaglandins may contribute to exercise-induced skeletal muscle arteriolar vasodilation in patients with heart failure. To test this hypothesis, we examined the effect of indomethacin on leg circulation and metabolism in eight chronic heart failure patients, aged 55 ± 4 yr. Central hemodynamics and leg blood flow, determined by thermodilution, and leg metabolic parameters were measured during maximum treadmill exercise before and 2 h after oral administration of indomethacin (75 mg). Leg release of 6-ketoprostaglandin F1α was also measured. During control exercise, leg blood flow increased from 0.34 ± 0.03 to 1.99 ± 0.19 l/min ( P < 0.001), leg O2 consumption from 13.6 ± 1.8 to 164.5 ± 16.2 ml/min ( P < 0.001), and leg prostanoid release from 54.1 ± 8.5 to 267.4 ± 35.8 pg/min ( P < 0.001). Indomethacin suppressed release of prostaglandin F1α( P < 0.001) throughout exercise and decreased leg blood flow during exercise ( P < 0.05). This was associated with a corresponding decrease in leg O2 consumption ( P < 0.05) and a higher level of femoral venous lactate at peak exercise ( P < 0.01). These data suggest that release of vasodilatory prostaglandins contributes to skeletal muscle arteriolar vasodilation in patients with heart failure.


2021 ◽  
Author(s):  
Dejan Simonovic ◽  
Stefano Coiro ◽  
Marina Deljanin‐Ilic ◽  
Masatake Kobayashi ◽  
Erberto Carluccio ◽  
...  

2004 ◽  
Vol 89 (3) ◽  
pp. 293-302 ◽  
Author(s):  
Darren S. DeLorey ◽  
Colin N. Shaw ◽  
J. Kevin Shoemaker ◽  
John M. Kowalchuk ◽  
Donald H. Paterson

2009 ◽  
Vol 11 (4) ◽  
pp. E14-E14 ◽  
Author(s):  
Sylvestre Maréchaux ◽  
Julia Terrade ◽  
Frédéric Biausque ◽  
Yann Lefetz ◽  
Régis Deturck ◽  
...  

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Jaroslav Meluzín ◽  
Josef Tomandl

Early heart failure with preserved ejection fraction (HFpEF) is a frequent disease, but its diagnosis is difficult and relies mostly on the evidence of left ventricular filling pressure (LVFP) elevation during exercise. Several reports have suggested that natriuretic peptides plasma levels reflect exercise-induced increase in LVFP, but they still have significant limitations. In this context, any new laboratory biomarker that can accurately reflect LVFP elevation during exercise is desirable. Recently, cardiotrophin-1, soluble endoglin, ST2, growth differentiation factor 15, galectin-3, and other new laboratory markers associated with LVFP have emerged. However, the current data on the relationship of these biomarkers and diastolic dysfunction are limited to resting conditions. Therefore, their secretion deserves to be tested under the exercise to determine their potential role in making a diagnosis of early HFpEF.


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