Is downstream cardiac testing required in patients with reduced functional capacity and otherwise negative exercise stress test? A single center observational study

Background: Exercise stress testing (EST) in patients with poor functional capacity measured by timeon treadmill is typically deemed inconclusive and usually leads to further downstream testing. The aimof this study was firstly to evaluate the maximum rate pressure product (MRPP) during initial EST toassessthe need for follow-up testing; and secondly to investigate if MRPP is better than age predictedmaximum heart rate (APMHR) for diagnostic outcome based on follow up cardiovascular (CV) eventsin patients with inconclusive EST due to poor functional capacity.Methods: From a total of 2761 tests performed, 236 tests were considered inconclusive due to poorfunctional capacity which were available for analysis. From receiver operating characteristic (ROC)analysis, a cut-off value for MRPP of 25000 was chosen using CV events as the outcome measure(sensitivity 97%, specificity 45%). Cases were then categorised into those with an MRPP > 25000 and< 25000.Results: Regardless of treadmill time, any patient attaining an MRPP > 25000 had no abnormaldownstream testing or CV events at 2 years follow-up. On ROC analysis MRPP outperformed APMHRfor sensitivity and specificity (area under curve 0.76 vs. 0.59, respectively).Conclusions: The results suggest that regardless of functional capacity, individuals whose EST is terminatedat maximal fatigue, with no electrocardiogram evidence or symptoms of myocardial ischemiaand yields an MRPP > 25000, do not require further downstream testing. Furthermore, this groupof patients, while not immune to future CV events, have significantly better outcomes than those notattaining a MRPP > 25000

Comparison of Heart Rate Blood Pressure Product Versus Age-Predicted Maximum Heart Rate as Predictors of Cardiovascular Events During Exercise Stress Echocardiography

Exercise stress echocardiograms (ESEs) are a functional cardiovascular (CV) test typically used for the investigation of coronary artery disease. ESEs are often terminated at a predetermined age-predicted maximum heart rate (APMHR) to facilitate timely acquisition of ultrasound images at peak exercise. Although an APMHR of 85% is often used, this has not been validated as a suitable termination end point. Heart rate blood pressure product (HRBPP) as an established measure of myocardial work may provide a more reliable assessment of cardiac workload. The aim of this study was to assess maximal HRBPP (MHRBPP) and APMHR as markers of cardiac workload during ESE, using CV events at mean follow-up as the outcome variable. After exclusions, 712 patients being investigated for ischemic heart disease, performed an ESE to volitional fatigue using the standard Bruce protocol. Patient demographics and test data were collected and patients followed for 4.4 ± 2.1 years. Cut-points for MHRBPP (25,060; area under curve 0.77) and APMHR (93.8% and 97.9%; area under curve 0.71; p = 0.12 for difference) were established from receiver operating characteristic analysis. Those achieving an APMHR >85% but MHRBPP 25,060 regardless of APMHR (

Regarding High Intensity Interval Training and Left Ventricular Mechanics

The influence of exercise on the mechanical function of the heart has become a topic of considerable interest over recent decades. In a recent issue of Medicine and Science in Sports and Exercise, Huang et al. (2) published a study that investigated the effects of high intensity interval training (HIIT) on echocardiographic-derived indices of left ventricular (LV) mechanical function in young, sedentary but otherwise healthy men. We believe that this study has the potential to further our understanding on how the heart responds to exercise, and it ultimately fits within the current knowledge on exercise-induced cardiac adaptation in health and disease (4). However, given the proposed conclusions, we would appreciate additional details from the authors on the methodology used that may have contributed to some unusual results. Specifically, this letter serves to highlight our concerns regarding the two most notable findings reported in the paper by Huang et al (2), namely 1) the unusually large increase in cardiorespiratory fitness following the HIIT intervention, and 2) the exceptionally low values derived from speckle tracking echocardiography

Oral contraceptives augment the exercise pressor reflex during isometric handgrip exercise

We sought to determine whether oral contraception alters the gender‐related differences observed in the exercise pressor reflex during isometric handgrip exercise. Fifteen men, fifteen normally menstruating women (WomenNM), and fifteen women taking monophasic oral contraceptives (WomenOC) completed two trials of a 3‐min isometric handgrip exercise protocol performed at 30% of their maximal voluntary contraction: (1) where arterial occlusion was applied to the previously exercising arm during a 3‐min recovery period (Occlusion trial); (2) where no arterial occlusion was applied during recovery (Control trial). Handgrip exercise elicited greater increases in mean arterial pressure (MAP) in MEN compared to both female groups (P < 0.05), and in WomenOC compared to WomenNM in both trials (P = 0.01, P = 0.03). After 3 min of recovery, sBP was 12% (P = 0.01) and 9% (P = 0.02) higher in the Occlusion trial when compared to the Control trial for MEN and WomenOC. Conversely, arterial occlusion in recovery from handgrip did not sustain elevated sBP in the Occlusion trial, and sBP returned to recovery levels not different to the Control trial, in WomenNM (P = 0.41). These data indicate that gender‐related differences in the metaboreflex during isometric handgrip exercise exist between men and normally menstruating women, but are blunted when men are compared to women taking oral contraceptives. We conclude that the suppression of 17β‐estradiol and/or progestogen in women via the administration of oral contraceptives attenuates sex‐related differences in the metaboreflex during isometric handgrip exercise

Physical properties of blood are altered in young and lean women with polycystic ovary syndrome

Classic features of polycystic ovary syndrome (PCOS) include derangement of metabolic and cardiovascular health, and vascular dysfunction is commonly reported. These comorbidities indicate impaired blood flow; however, other than limited reports of increased plasma viscosity, surprisingly little is known regarding the physical properties of blood in PCOS. We aimed to investigate whether haemorheology was impaired in women with PCOS. We thus measured a comprehensive haemorheological profile, in a case-control design, of lean women with PCOS and age-matched healthy controls. A clinical examination determined similar cardiovascular risk for the two groups. Whole blood and plasma viscosity was measured using a cone-plate viscometer. The magnitude and rate of red blood cell (RBC) aggregation was determined using a light-transmission aggregometer, and the degree of RBC deformability was measured via laser-diffraction ektacytometry. Plasma viscosity was significantly increased in women with PCOS. Blood viscosity was also increased for PCOS at lower-to-moderate shear rates in both native and standardised haematocrit samples. The magnitude of RBC aggregation–a primary determinant of low-shear blood viscosity–was significantly increased in PCOS at native and 0.4 L·L(-1) haematocrit. No difference was detected between PCOS and CON groups for RBC deformability measurements. A novel measure indicating the effectiveness of oxygen transport by RBC (i.e., the haematocrit-to-viscosity ratio; HVR) was decreased at all shear rates in women with PCOS. In a group of young and lean women with PCOS with an unremarkable cardiovascular risk profile based on clinical data, significant haemorheological impairment was observed. The degree of haemorheological derangement observed in the present study reflects that of overt chronic disease, and provides an avenue for future therapeutic intervention in PCOS

Muscle fiber typology is associated with the incidence of overreaching in response to overload training

The aim of this study was to identify markers of training stress and characteristics of middle-distance runners related to the incidence of overreaching following overload training. Twenty-four highly-trained runners (n=16 male; VO2peak=73.3(4.3) mL·kg·min-1; n=8 female, VO2peak=63.2(3.4) mL·kg·min-1) completed 3 weeks of normal training (NormTr), 3 weeks of high-volume training (HVTr; a 10, 20 and 30% increase in training volume each successive week from NormTr), and a 1-week taper (TapTr; 55% exponential reduction in training volume from HVTr week 3). Before, and immediately after each training period, an incremental treadmill-running test was performed, while resting metabolic rate (RMR), subjective fatigue responses and various resting blood biomarkers were assessed. Muscle fiber typology of the gastrocnemius was estimated by quantification of muscle carnosine using proton magnetic resonance spectroscopy and expressed as a z-score relative to a non-athlete control group. Twelve runners were classified as functionally overreached (FOR) following HVTr (decreased running TTE), whereas the other twelve were classified as acutely fatigued (AF; no decrease in running TTE). The FOR group did not demonstrate systematic alterations in RMR, resting blood biomarkers or submaximal exercise responses compared to the AF group. Gastrocnemius carnosine z-score was significantly higher in FOR (-0.44 ± 0.57) compared to AF (-1.25 ± 0.49, p = 0.004, d = 1.53) and was also associated with changes in running TTE from pre- to post-HVTr (r=-0.55, p=0.005) and pre-HVTr to post-TapTr (r=-0.64, p=0.008). Muscle fiber typology is related to the incidence of overreaching and performance super-compensation following increased training volume and a taper

Time-course Of Transcriptomic Responses In Skeletal Muscle During Recovery From Endurance Exercise Indicates Prolonged Muscular Inflammation

Introduction Re-programming of gene expression is fundamental for skeletal muscle adaptations in response to endurance exercise. Although inflammatory responses in muscle following muscle-damaging exercise can persist for days, there is a paucity of global gene expression data beyond 48 hours following exercise. This study aimed to investigate the changes in the transcriptome of skeletal muscle until 96 hours after an endurance exercise trial (EXTRI; one hour of cycling followed by one hour of running). Data on the transcriptome of circulating neutrophils from participants in the current study indicated that the neutrophil transcriptional activity was related to the muscle-damaging component of the EXTRI (Neubauer et al. 2013, J Appl Physiol.). We hypothesised that the muscular transcriptome would particularly reflect interactions between muscle and infiltrating leukocytes. Methods Eight healthy, endurance-trained, male individuals participated. Skeletal muscle samples were taken one week before the EXTRI, 3, 48, and 96 hours post-EXTRI. RNA was extracted from muscle tissue. Differential gene expression was evaluated using Illumina microarrays, and validated with q-PCR. Gene set enrichment analysis identified functionally related gene sets chosen from the Molecular Signatures Database. Results Significantly (FWER p-value Conclusions The current data indicate that many of the coordinated gene expression responses in skeletal muscle, particularly at 96 hours post-EXTRI, were related with exercise-induced muscle damage, and the subsequent accumulation of muscle leukocytes. The substantial transcriptional activity 96 h post-EXTRI was strongly associated with inflammatory and immune responses, and suggests that muscular recovery, from a transcriptional perspective, is incomplete 96 hours after exercise

Exercise-induced blood lactate increase does not change red blood cell deformability in cyclists.

BACKGROUND: The effect of exercise-induced lactate production on red blood cell deformability and other blood rheological changes is controversial, given heavy-exercise induces biochemical processes (e.g., oxidative stress) known to perturb haemorheology. The aim of the present study was to examine the haemorheological response to a short-duration cycling protocol designed to increase blood lactate concentration, but of duration insufficient to induce significant oxidative stress. METHODS: Male cyclists and triathletes (n = 6; 27±7 yr; body mass index: 23.7±3.0 kg/m²; peak oxygen uptake 4.02±0.51 L/min) performed unloaded (0 W), moderate-intensity, and heavy-intensity cycling. Blood was sampled at rest and during the final minute of each cycling bout. Blood chemistry, blood viscosity, red blood cell aggregation and red blood cell deformability were measured. RESULTS: Blood lactate concentration increased significantly during heavy-intensity cycling, when compared with all other conditions. Methaemoglobin fraction did not change during any exercise bout when compared with rest. Blood viscosity at native haematocrit increased during heavy-intensity cycling at higher-shear rates when compared with rest, unloaded and moderate-intensity cycling. Heavy-intensity exercise increased the amplitude of red blood cell aggregation in native haematocrit samples when compared with all other conditions. Red blood cell deformability was not changed by exercise. CONCLUSION: Acute exercise perturbs haemorheology in an intensity dose-response fashion; however, many of the haemorheological effects appear to be secondary to haemoconcentration, rather than increased lactate concentration

Handrail support produces a higher rate pressure product in apparently healthy non-treadmill users during maximal exercise testing

Objective: Exercise treadmill testing (ETT) is a well-established procedure for the diagnosis, prognosis and functional assessment of patients with suspected cardiovascular disease. The use of handrail support during ETT is often discouraged as this has been demonstrated to overestimate functional capacity. It is unknown if this increase in functional capacity translates to an increase in cardiac workload. The aim of this study was to investigate if the use of handrail support during maximal ETT produces an increase in cardiac workload when compared to no handrail support. Approach: Fifty-two consenting volunteers performed two maximal ETTs, one with handrail support and the other without, approximately one week apart. Participants were identified as either experienced treadmill users (treadmill use >= once per fortnight) (n = 24) or inexperienced users (n = 28). Cardiac workload was quantified using rate pressure product (RPP) (systolic blood pressure (SBP) x heart rate (HR)) Main results: The average age of participants was 38.4 +/- 11.4 years (44% male). Overall exercise duration was significantly prolonged by 44.4% with handrail support (with support 15:01 +/- 2:54 min; without support 10:24 +/- 2:09 min). Overall HR, SBP and maximum RPP were not significantly different between conditions. For the 28 inexperienced treadmill users maximum RPP was significantly higher during handrail support (7.5% increase) (with support 34 417 +/- 4906; without support 31 821 +/- 4565). Significance: Handrail support overestimates functional capacity, however produces greater maximal RPP in inexperienced treadmill users. If accurate aerobic data is required during ETT, or subjects performing ETT are experienced treadmill users, handrail support should be discouraged. Non-treadmill users or subjects fearful of falling may benefit from handrail support, particularly when maximal cardiac workload is desired