Exercise-induced arterial hypoxaemia in patients with heart failure with preserved ejection fraction.

Some patients with heart failure with preserved ejection fraction (HFpEF) have demonstrated evidence of exercise-induced arterial hypoxaemia (EIAH). However, EIAH was not quantified using , , and measurements as previously conducted in healthy adults nor was EIAH quantified alongside simultaneous measurements of pulmonary vascular pressures, cardiorespiratory responses, or dyspnoea on exertion (DOE) in these patients. Given the effects of hypoxaemia on pulmonary vasoconstriction, cardiorespiratory responses, and DOE, we tested the hypothesis that patients with HFpEF and EIAH (EIAH) would demonstrate higher pulmonary vascular pressures, worse oxygen uptake, and greater DOE compared with patients without EIAH (EIAH).

Microvascular Function and Ambulatory Capacity in Peripheral Artery Disease.

Background: Patients with peripheral artery disease experience walking impairment that is incompletely explained by large-artery atherosclerotic occlusive disease and abnormal ankle-brachial index (ABI). Microvascular dysfunction is associated with adverse outcomes, including amputation, but its effect on ambulation is unknown. We tested the hypothesis that skeletal muscle microvascular function directly associates with walking distance, is a more sensitive indicator of walking distance than conduit artery blood inflow, and correlates with ambulatory improvement following peripheral artery disease interventions.

Regional and systemic adipose mass and peripheral conduit artery function.

Introduction: Vascular function and metabolic function are inherently coupled. While prior studies have linked body mass index (BMI) and visceral adiposity to reduced FMD, the relationship between whole-body and limb-specific adiposity and vascular function in adults with pre-diabetic levels of insulin resistance remains unclear.

Methods: We assessed body composition (DEXA), insulin resistance (HOMA-IR and Matsuda Index), and brachial artery FMD in 93 pre-diabetic individuals (69 % Female) aged 18-65 with obesity (BMI ≥ 30 kg/m).

Exercise blood pressure in adults with high-risk left ventricular hypertrophy: the importance of normalizing blood pressure to oxygen uptake.

Introduction: Exaggerated exercise blood pressure (EEBP) is typically defined using systolic blood pressure (SBP) thresholds at maximal exercise of ≥190 (women) and ≥210 mmHg (men). However, SBP/workload and SBP/oxygen uptake (V̇O 2 ) slopes have been shown to be more sensitive predictors of all-cause mortality and/or cardiovascular morbidity than peak exercise SBP. Hypertensive adults with left ventricular hypertrophy (LVH) often present with EEBP; whether the change in SBP with exercise is also greater when normalized for workload/V̇O 2 is unknown.

Heart-Lung Interactions in HFpEF: Dynamic Hyperinflation and Exercise PCWP.

Background: Patients with heart failure with preserved ejection fraction (HFpEF) are characterized by an exaggerated rise in pulmonary capillary wedge pressure (PCWP) with exercise compared with healthy similar-aged adults. Due to the multisystemic effects of the disease, patients with HFpEF often experience expiratory flow limitation (EFL), thereby perpetuating dynamic hyperinflation (DH) and ventilation at a higher percentage of total lung volume. How lung mechanics and operational lung volume affect central hemodynamics in patients with HFpEF is not fully understood.

Impaired exercise hemodynamic responses in patients with HFpEF without a sympathetic vasoconstrictor reserve.

Impaired exercise hyperemia and blunted vasoconstrictor responsiveness have been reported in patients with heart failure with preserved ejection fraction (HFpEF). However, there is considerable heterogeneity in the degree to which vasodilatory capacity and sympathetic vasoconstrictor reserve are diminished. Given the integration of both vasodilation and vasoconstriction to appropriately regulate blood flow during exercise, we hypothesized that patients with HFpEF who are unable to vasoconstrict to sympatho-excitation (i.

Functional sympatholysis of neuropeptide Y-mediated vasoconstriction in humans.

Metabolic inhibition of sympathetic vasoconstriction (functional sympatholysis) is essential for adequate perfusion of skeletal muscle during exercise. Neuropeptide Y (NPY) is a neurotransmitter that elicits potent vasoconstriction and is co-released with noradrenaline during sympathoexcitation. NPY is released from sympathetic nerves during exercise; however, no study has assessed whether NPY-mediated vasoconstriction is sensitive to metabolic inhibition in humans.

Circumferential strain and strain rates of the descending aorta as novel measures of aortic stiffness and wall mechanics from standard cardiac MRI.

During standard cardiovascular magnetic resonance (CMR) the horizontal long-axis cine image (i.e., 4-chamber) is captured which includes a cross-section of the descending aorta.

Maintained sympathetic reactivity but blunted pressor response to static handgrip exercise in heart failure with preserved ejection fraction.

Purpose: Recent studies have reported blunted increases in blood pressure (BP) during static handgrip (SHG) in patients with heart failure with preserved ejection fraction (HFpEF), which may be attributed to abnormal sympathetic reactivity during exercise and/or impaired muscle metaboreflex function. However, it is unknown whether the sympathetic neural response to SHG and isolated muscle metaboreflex activation via post-exercise circulatory occlusion (PECO) are attenuated in HFpEF.

Methods: Thirty-nine patients with HFpEF and 24 age-matched non-HFpEF controls were studied in the supine position.

Effect of Acute Resistance Exercise and Resistance Exercise Training on Central Pulsatile Hemodynamics and Large Artery Stiffness: Part I.

Background: Engaging in habitual resistance exercise training (RET; also known as strength training) causes systemic health effects beyond those caused by aerobic/endurance exercise training alone. Despite the resoundingly favorable effect of habitual RET on measures of cardiovascular disease risk, controversy still exists regarding the vascular health effects of this exercise modality largely because some studies find increases in large artery stiffness and central pulsatile hemodynamics with RET. In this two-part series, we examine the effect of acute resistance exercise (RE) and RET on large artery stiffness and pulsatile hemodynamics.

Effect of Acute Resistance Exercise and Resistance Exercise Training on Central Pulsatile Hemodynamics and Large Artery Stiffness: Part II.

Background: In part one of this two-part series, we performed a detailed analysis of the hemodynamic signature produced during resistance exercise (RE) and discussed the subacute effects on short-term modulation of large artery stiffness and central pulsatile hemodynamics. In this second part of our two-part series, we consider the subacute recovery window as the driver of resistance exercise training (RET) adaptations. We then discuss the results of RET interventions and corroborate these findings against the information gleaned from cross-sectional studies in habitually strength-trained athletes.

Pulmonary gas exchange in relation to exercise pulmonary hypertension in patients with heart failure with preserved ejection fraction.

Background: Exercise pulmonary hypertension, defined as a mean pulmonary arterial pressure (mPAP)/cardiac output () slope >3 WU during exercise, is common in patients with heart failure with preserved ejection fraction (HFpEF). However, the pulmonary gas exchange-related effects of an exaggerated exercise pulmonary hypertension (EePH) response are not well defined, especially in relation to dyspnoea on exertion and exercise intolerance.

Methods: 48 HFpEF patients underwent invasive (pulmonary and radial artery catheters) constant-load (20 W) and maximal incremental cycle testing.

Identifying the Mechanisms of a Peripherally Limited Exercise Phenotype in Patients With Heart Failure With Preserved Ejection Fraction.

Background: We identified peripherally limited patients using cardiopulmonary exercise testing and measured skeletal muscle oxygen transport and utilization during invasive single leg exercise testing to identify the mechanisms of the peripheral limitation.

Methods: Forty-five patients with heart failure with preserved ejection fraction (70±7 years, 27 females) completed seated upright cardiopulmonary exercise testing and were defined as having a (1) peripheral limitation to exercise if cardiac output/oxygen consumption (VO) was elevated (≥6) or 5 to 6 with a stroke volume reserve >50% (n=31) or (2) a central limitation to exercise if cardiac output/VO slope was ≤5 or 5 to 6 with stroke volume reserve <50% (n=14). Single leg knee extension exercise was used to quantify peak leg blood flow (Doppler ultrasound), arterial-to-venous oxygen content difference (femoral venous catheter), leg VO, and muscle oxygen diffusive conductance.

Impaired longitudinal systolic-diastolic coupling and cardiac response to exercise in patients with hypertrophic cardiomyopathy.

Background: In patients with hypertrophic cardiomyopathy (HCM), impaired augmentation of stroke volume and diastolic dysfunction contribute to exercise intolerance. Systolic-diastolic (S-D) coupling characterizes how systolic contraction of the left ventricle (LV) primes efficient elastic recoil during early diastole. Impaired S-D coupling may contribute to the impaired cardiac response to exercise in patients with HCM.

The effect of chronic habitual exercise on oxygen carrying capacity and blood compartment volumes in older adults.

Absolute total hemoglobin mass (tHbmass) and blood compartment volumes are often considered to be higher in endurance athletes compared with nonathletes, yet little data support a fitness effect in older age. Therefore, we measured tHbmass and blood compartment volumes (carbon monoxide rebreathing) in 77 healthy individuals (23% female; aged, 60-87 yr). Participants were recruited into groups based upon their lifelong (>25 yr) exercise "dose": ) 15 sedentary individuals, <2 sessions/wk; ) 25 casual exercisers, 2-3 sessions/wk; ) 24 committed exercisers, 4-5 sessions/wk; and ) 13 competitive Masters athletes, 6-7 sessions/wk, plus regular competitions.

Effects of Synchronizing Foot Strike and Cardiac Phase on Exercise Hemodynamics in Patients With Cardiac Resynchronization Therapy: A Within-Subjects Pilot Study to Fine-Tune Cardio-Locomotor Coupling for Heart Failure.

Background: Despite advances in medical and cardiac resynchronization therapy (CRT), individuals with chronic congestive heart failure (CHF) have persistent symptoms, including exercise intolerance. Optimizing cardio-locomotor coupling may increase stroke volume and skeletal muscle perfusion as previously shown in healthy runners. Therefore, we tested the hypothesis that exercise stroke volume and cardiac output would be higher during fixed-paced walking when steps were synchronized with the diastolic compared with systolic portion of the cardiac cycle in patients with CHF and CRT.

Cardiac Effects of Long-Duration Space Flight.

Background: Ventricular mass responds to changes in physical activity and loading, with cardiac hypertrophy after exercise training, and cardiac atrophy after sustained inactivity. Ventricular wall stress (ie, loading) decreases during microgravity. Cardiac atrophy does not plateau during 12 weeks of simulated microgravity but is mitigated by concurrent exercise training.

Aortic stiffness contributes to greater pressor responses during static hand grip exercise in healthy young and middle-aged normotensive men.

Central arterial stiffness can influence exercise blood pressure (BP) by increasing the rise in arterial pressure per unit increase in aortic inflow. Whether central arterial stiffness influences the pressor response to isometric handgrip exercise (HG) and post-exercise muscle ischemia (PEMI), two common laboratory tests to study sympathetic control of BP, is unknown. We studied 46 healthy non-hypertensive males (23 young and 23 middle-aged) during HG (which increases in cardiac output [Q̇c]) and isolated metaboreflex activation PEMI (no change or decreases in Q̇c).

Reducing Pulmonary Capillary Wedge Pressure During Exercise Exacerbates Exertional Dyspnea in Patients With Heart Failure With Preserved Ejection Fraction: Implications for V˙/Q˙ Mismatch.

Background: The primary cause of dyspnea on exertion in heart failure with preserved ejection fraction (HFpEF) is presumed to be the marked rise in pulmonary capillary wedge pressure during exercise; however, this hypothesis has never been tested directly. Therefore, we evaluated invasive exercise hemodynamics and dyspnea on exertion in patients with HFpEF before and after acute nitroglycerin (NTG) treatment to lower pulmonary capillary wedge pressure.

Research Question: Does reducing pulmonary capillary wedge pressure during exercise with NTG improve dyspnea on exertion in HFpEF?

Study Design And Methods: Thirty patients with HFpEF performed two invasive 6-min constant-load cycling tests (20 W): one with placebo (PLC) and one with NTG.

Challenging the Hemodynamic Hypothesis in Heart Failure With Preserved Ejection Fraction: Is Exercise Capacity Limited by Elevated Pulmonary Capillary Wedge Pressure?

Background: Exercise intolerance is a defining characteristic of heart failure with preserved ejection fraction (HFpEF). A marked rise in pulmonary capillary wedge pressure (PCWP) during exertion is pathognomonic for HFpEF and is thought to be a key cause of exercise intolerance. If true, acutely lowering PCWP should improve exercise capacity.

Aortic haemodynamics: the effects of habitual endurance exercise, age and muscle sympathetic vasomotor outflow in healthy men.

Purpose: We determined the effect of habitual endurance exercise and age on aortic pulse wave velocity (aPWV), augmentation pressure (AP) and systolic blood pressure (aSBP), with statistical adjustments of aPWV and AP for heart rate and aortic mean arterial pressure, when appropriate. Furthermore, we assessed whether muscle sympathetic nerve activity (MSNA) correlates with AP in young and middle-aged men.

Methods: Aortic PWV, AP, aortic blood pressure (applanation tonometry; SphygmoCor) and MSNA (peroneal microneurography) were recorded in 46 normotensive men who were either young or middle-aged and endurance-trained runners or recreationally active nonrunners (10 nonrunners and 13 runners within each age-group).