Rhys Beaudry

A Modern Definition of the Athlete’s Heart—for Research and the Clinic

Exercise training can have a profound effect on cardiac structure. Recent evidence suggests that the greatest determinants of exercise-induced cardiac remodeling are the intensity, duration, and frequency of training. This also has overlap with athlete fitness. There are many additional factors that are important in determining cardiac remodeling, but while further refinements evolve, the authors argue that the best means of predicting the degree of expected physiologic remodeling is to either quantify training (intensity times total training time) or its by-product (exercise capacity). A uniform approach to estimating the degree of exercise-induced cardiac remodeling will enable more consistent research.

Modulation of resistance artery tone by the trace amine β-phenylethylamine: dual indirect sympathomimetic and α1-adrenoceptor blocking actions

The trace amine β-phenylethylamine (PEA) is normally present in the body at low nanomolar concentrations but can reach micromolar levels after ingestion of drugs that inhibit monoamine oxidase and primary amine oxidase. In vivo, PEA elicits a robust pressor response, but there is no consensus regarding the underlying mechanism, with both vasodilation and constriction reported in isolated blood vessels. Using functional and biochemical approaches, we found that at low micromolar concentrations PEA (1–30 μM) enhanced nerve-evoked vasoconstriction in the perfused rat mesenteric bed but at a higher concentration (100 μM) significantly inhibited these responses. The α2-adrenoceptor antagonist rauwolscine (1 µM) also enhanced nerve-mediated vasoconstriction, but in the presence of both rauwolscine (1 µM) and PEA (30 µM) together, nerve-evoked responses were initially potentiated and then showed time-dependent rundown. PEA (10 and 100 μM) significantly increased noradrenaline outflow from the mesenteric bed as determined by high-pressure liquid chromatography coupled with electrochemical detection. In isolated endothelium-denuded arterial segments, PEA (1 µM to 1 mM) caused concentration-dependent reversal of tone elicited by the α1-adrenoceptor agonists noradrenaline (EC50 51.69 ± 10.8 μM; n = 5), methoxamine (EC50 68.21 ± 1.70 μM; n = 5), and phenylephrine (EC50 67.74 ± 16.72 μM; n = 5) but was ineffective against tone induced by prostaglandin F2α or U46619 (9,11-dideoxy-9α,11α-methanoepoxyprostaglandin F2α). In rat brain homogenates, PEA displaced binding of both [3H]prazosin (Ki ≈ 25 μM) and [3H]rauwolscine (Ki ≈ 1.2 μM), ligands for α1- and α2-adrenoceptors, respectively. These data provide the first demonstration that dual indirect sympathomimetic and α1-adrenoceptor blocking actions underlie the vascular effects of PEA in resistance arteries.

Diastolic stress testing: similarities and differences between isometric handgrip and cycle echocardiography

Cycle echocardiography (CE) is recommended for noninvasive diagnosis of diastolic dysfunction but can be limited by respiratory and movement artifact. Isometric handgrip echocardiography (IHE) is also a robust diastolic discriminator, while avoiding the limitations associated with dynamic exercise. This study sought to compare these two diastolic stress testing approaches. Twelve elderly individuals were recruited from the community (age 71 ± 6 yr). Heart rate, arterial blood pressure, and left ventricular (LV) diastolic function (via echocardiography) were assessed at rest and in response to 3 min of IHE at 40% of their maximal voluntary contraction, followed by 3 min of CE at 20 W. Both IHE and CE caused a significant increase in heart rate and blood pressure, leading to similar increases in myocardial oxygen demand. Both stressors also evoked a similar rise in the ratio between early LV mitral inflow velocity to early lateral annular velocity, a surrogate measure of LV filling pressure. The underlying mechanisms leading to these changes, however, were inherently different. IHE increased mean arterial pressure, and impaired myocardial relaxation, to a greater extent than CE. In contrast, CE augmented cardiac index, and increased early mitral filling velocity, to a great extent than IHE. In conclusion, for the first time, these data highlight several important similarities and differences between IHE and CE. That IHE avoids respiratory and movement artifact, while still serving as a robust diastolic discriminator, supports IHE as a strong alternative to CE for diastolic stress testing. NEW & NOTEWORTHY This is the first study to compare the diastolic stress response between isometric handgrip exercise and conventional cycle exercise. The data suggest that isometric handgrip echocardiography is comparable to conventional cycle echocardiography, both in terms of its hemodynamic challenge and global diastolic stress response. That isometric handgrip echocardiography eliminates both respiratory and movement artifact and is low cost and incredibly portable supports its integration into routine echocardiography exams.

Isometric handgrip echocardiography: A noninvasive stress test to assess left ventricular diastolic function

Cycle exercise echocardiography is a useful tool to “unmask” diastolic dysfunction; however, this approach can be limited by respiratory and movement artifacts. Isometric handgrip avoids these issues while reproducibly increasing afterload and myocardial oxygen demand.

Pathophysiology of exercise intolerance in breast cancer survivors with preserved left ventricular ejection fraction.

Breast cancer (BC) survival rates have improved during the past two decades and as a result older BC survivors are at increased risk of developing heart failure (HF). Although the HF phenotype common to BC survivors has received little attention, BC survivors have a number of risk factors associated with HF and preserved ejection fraction (HFPEF) including older age, hypertension, obesity, metabolic syndrome and sedentary lifestyle. Moreover, not unlike HFPEF, BC survivors with preserved left ventricular ejection fraction (BCPEF) have reduced exercise tolerance measured objectively as decreased peak oxygen uptake (peak VO2). This review summarizes the literature regarding the mechanisms of exercise intolerance and the role of exercise training to improve peak VO2 in BCPEF.

Meta-analysis of Exercise Training on Vascular Endothelial Function in Cancer Survivors:

Cancer and cardiovascular disease (CVD) are leading causes of morbidity and mortality in the United States. Vascular endothelial dysfunction, an important contributor in the development of CVD, improves with exercise training in patients with CVD. However, the role of regular exercise to improve vascular function in cancer survivors remains equivocal. We performed a meta-analysis to determine the effect of exercise training on vascular endothelial function in cancer survivors. We searched PubMed (1975 to 2016), EMBASE CINAHL (1937 to 2016), OVID MEDLINE (1948 to 2016), and Cochrane Central Registry of Controlled Trials (1991 to 2016) using search terms: vascular function, endothelial function, flow-mediated dilation [FMD], reactive hyperemia, exercise, and cancer. Studies selected were randomized controlled trials of exercise training on vascular endothelial function in cancer survivors. We calculated pooled effect sizes and performed a meta-analysis. We identified 4 randomized controlled trials (breast cancer, n=2; prostate cancer, n=2) measuring vascular endothelial function by FMD (n=3) or reactive hyperemia index (n=1), including 163 cancer survivors (exercise training, n=82; control, n=81). Aerobic exercise training improved vascular function (n=4 studies; standardized mean difference [95% CI]=0.65 [0.33, 0.96], I2=0%; FMD, weighted mean difference [WMD]=1.28 [0.22, 2.34], I2=23.2%) and peak exercise oxygen uptake (3 trials; WMD [95% CI]=2.22 [0.83, 3.61] mL/kg/min; I2=0%). Our findings indicate that exercise training improves vascular endothelial function and exercise capacity in breast and prostate cancer survivors.

Meta-analysis of Exercise Training on Left Ventricular Ejection Fraction in Heart Failure with Reduced Ejection Fraction: A 10-year Update

BACKGROUND The role of exercise training modality to attenuate left ventricular (LV) remodeling in heart failure patients with reduced ejection fraction (HFrEF) remains uncertain. The authors performed a systematic review and meta-analysis of published reports on exercise training (moderate-intensity continuous aerobic, high-intensity interval aerobic, and resistance exercise) and LV remodeling in clinically stable HFrEF patients. METHODS We searched MEDLINE, Cochrane Central Registry of Controlled Trials, CINAHL, and PubMed (2007 to 2017) for randomized controlled trials of exercise training on resting LV ejection fraction (EF) and end-diastolic and end-systolic volumes in HFrEF patients. RESULTS 18 trials reported LV ejection fraction (LVEF) data, while 8 and 7 trials reported LV end-diastolic and LV end-systolic volumes, respectively. Overall, moderate-intensity continuous training (MICT) significantly increased LVEF (weighted mean difference, WMD = 3.79%; 95% confidence interval, CI, 2.08 to 5.50%) with no change in LV volumes versus control. In trials ≥6 months duration, MICT significantly improved LVEF (WMD = 6.26%; 95% CI 4.39 to 8.13%) while shorter duration (<6 months) trials modestly increased LVEF (WMD = 2.33%; 95% CI 0.84 to 3.82%). High-intensity interval training (HIIT) significantly increased LVEF compared to control (WMD = 3.70%; 95% CI 1.63 to 5.77%) but was not different than MICT (WMD = 3.17%; 95% CI -0.87 to 7.22%). Resistance training performed alone or combined with aerobic training (MICT or HIIT) did not significantly change LVEF. CONCLUSIONS In clinically stable HFrEF patients, MICT is an effective therapy to attenuate LV remodeling with the greatest benefits occurring with long-term (≥6 months) training. HIIT performed for 2 to 3 months is superior to control, but not MICT, for improvement of LVEF.

Diastolic Stress Testing Along the Heart Failure Continuum

Purpose of ReviewThis review summarizes recent developments highlighting the clinical utility of diastolic stress testing along the heart failure continuum.Recent FindingsInvasive hemodynamic assessment of cardiac filling pressures during physiological stress is the gold-standard technique for unmasking diastolic dysfunction. Non-invasive surrogate techniques, such as Doppler ultrasound, have shown excellent agreement with invasive approaches and are now recommended by the American Society of Echocardiography and the European Association of Cardiovascular Imaging. While cycle exercise is often advocated, recent evidence supports the use of isometric handgrip as a viable alternative stressor.SummaryDiastolic stress testing is a powerful tool to enhance detection of diastolic dysfunction, is able to differentiate between cardiac and non-cardiac pathology, and should be incorporated into routine clinical assessment.

Exercise cardiac magnetic resonance imaging: a feasibility study and meta-analysis

Cardiac stress testing improves detection and risk assessment of heart disease. Magnetic resonance imaging (MRI) is the clinical gold-standard for assessing cardiac morphology and function at rest; however, exercise MRI has not been widely adapted for cardiac assessment because of imaging and device limitations. Commercially available magnetic resonance ergometers, together with improved imaging sequences, have overcome many previous limitations, making cardiac stress MRI more feasible. Here, we aimed to demonstrate clinical feasibility and establish the normative, healthy response to supine exercise MRI. Eight young, healthy subjects underwent rest and exercise cinematic imaging to measure left ventricular volumes and ejection fraction. To establish the normative, healthy response to exercise MRI we performed a comprehensive literature review and meta-analysis of existing exercise cardiac MRI studies. Results were pooled using a random effects model to define the left ventricular ejection fraction, end-diastolic, end-systolic, and stroke volume responses. Our proof-of-concept data showed a marked increase in cardiac index with exercise, secondary to an increase in both heart rate and stroke volume. The change in stroke volume was driven by a reduction in end-systolic volume, with no change in end-diastolic volume. These findings were entirely consistent with 17 previous exercise MRI studies (226 individual records), despite differences in imaging approach, ergometer, or exercise type. Taken together, the data herein demonstrate that exercise cardiac MRI is clinically feasible, using commercially available exercise equipment and vendor-provided product sequences and establish the normative, healthy response to exercise MRI.

Erratum regarding incorrect spelling of author name

Heart failure with preserved ejection (HFpEF) accounts for over 50 % of all HF cases, and the proportion is higher among women and older individuals. A hallmark feature of HFpEF is dyspnoea on exertion and reduced peak aerobic power (VO2peak) secondary to central and peripheral abnormalities that result in reduced oxygen delivery to and/or utilisation by exercising skeletal muscle. The purpose of this brief review is to discuss the role of exercise training to improve VO2peak and the central and peripheral adaptations that reduce symptoms following physical conditioning in patients with HFpEF.