Philippe Obert

Alteration in left ventricular normal and shear strains evaluated by 2D-strain echocardiography in the athlete's heart

The contraction of cardiomyocytes induces a systolic increase in left ventricular (LV) normal (radial, circumferential and longitudinal) and shear strains, whose functional consequences have not been evaluated, so far, in athletes. We used 2D ultrasound speckle tracking imaging (STI) to evaluate LV regional strain in high‐level cyclists compared to sedentary controls. Sixteen male elite cyclists and 23 sedentary controls underwent conventional, tissue Doppler, and STI echocardiography at rest. We assessed LV long and short axis normal strains and shear strains. We evaluated circumferential–longitudinal shear strain from LV torsion, and circumferential–radial shear strain from the difference between subendocardial and subepicardial torsion. Apical radial strain (42.7 ± 10.5%versus 52.2 ± 14.3%, P < 0.05) and LV torsion (6.0 ± 1.8 deg versus 9.2 ± 3.2 deg, P < 0.01) were lower in cyclists than in controls, respectively. Rotations and torsion were higher in the subendocardial than in the subepicardial region in sedentary controls, but not in cyclists. Haemodynamic and tissue Doppler based indexes of global LV diastolic and systolic functions were not different between cyclists and controls. Athletes heart is associated with specific LV adaptation including lower apical strain and lower myocardial shear strains, with no change in global LV diastolic and systolic function. These mechanical alterations could improve the cardiovascular adjustments to exercise by increasing the radial strain and torsional (and thus untwisting) response to exercise, a key element of diastolic filling and thus of cardiac performance in athletes.

Alteration in Left Ventricular Strains and Torsional Mechanics After Ultralong Duration Exercise in Athletes

Background—Numerous studies have reported evidence of cardiac injury associated with transient left ventricular (LV) systolic and diastolic dysfunction after prolonged and strenuous exercise. We used 2D ultrasound speckle tracking imaging to evaluate the effect of an ultralong-duration exercise on LV regional strains and torsion. We speculated that systolic dysfunction after exercise is associated with depressed LV strains and torsion, and diastolic dysfunction results from decreased and delayed untwisting, a key factor of LV suction and early filling. Methods and Results—Twenty-three triathletes underwent conventional and speckle tracking imaging echocardiography at rest before and immediately after an ultralong distance triathlon. Measurements included LV longitudinal, circumferential and radial strains, LV rotations, and LV torsion. After the race, LV systolic dysfunction was characterized by a decrease in LV longitudinal, radial, and circumferential strains, especially for apical radial strains (44.6±15.1% versus 31.1±13.8%, P<0.001). Peak torsion was slightly decreased (8.3±5.1° versus 6.4±3.9°, respectively, P=0.09) and significantly delayed (91±18% versus 128±31% of systolic duration, P<0.001) beside end-ejection. Peak untwisting was also depressed and delayed beside isovolumic relaxation. Conclusions—This study documented major alterations in cardiac strains and torsion after an ultralong distance triathlon. LV systolic strains were depressed but not delayed, whereas twisting was decreased and delayed. This altered pattern hampered the rapid untwisting during isovolumic relaxation phase, reducing LV diastolic suction and early filling.

Kinetics of left ventricular strains and torsion during incremental exercise in healthy subjects: the key role of torsional mechanics for systolic-diastolic coupling.

Background—The dynamics of systolic and diastolic strains and torsional mechanics of the left ventricle (LV) and their relation to diastolic filling never have been evaluated at various exercise intensities. Methods and Results—Speckle tracking echocardiography was performed in 20 healthy sedentary subjects at rest and during a progressive submaximal exercise test at 20%, 30%, and 40% of maximal aerobic power. LV twist increased progressively with exercise intensity (10.5±3.2 to 15.8±4.5°; P<0.001), whereas longitudinal strain remained unchanged after the first workload, underlining the key role of torsional reserve in systolic-diastolic coupling during exercise. The increase in diastolic untwisting (−88.7±34.2 to −182.9±53.5 deg · s−1; P<0.01) was correlated to enhanced systolic twist (R=0.61; P<0.001), and its magnitude of increase was significantly higher compared to diastolic longitudinal and circumferential strain rates (119±64% versus 65±44% and 57±24%, respectively), emphasizing its contribution to diastolic filling. The timing of peak untwisting and the chronology of diastolic mechanical events were unchanged during effort. Untwisting was driven mainly by apical rotation and determined mitral opening and isovolumic relaxation time (R=0.47 and 0.61, respectively; P<0.001), whereas basal rotation and longitudinal and circumferential diastolic strain rates were major determinants of increased early diastolic filling (R=0.64, 0.79, and 0.81, respectively; P<0.001). Conclusions—The use of speckle tracking echocardiography gives new insights into physiological adaptive LV mechanics during incremental exercise in healthy subjects, underlining the key role of torsional mechanics. It might be useful to better understand the mechanisms of diastolic dysfunction and exercise intolerance in various pathological conditions.Background— The dynamics of systolic and diastolic strains and torsional mechanics of the left ventricle (LV) and their relation to diastolic filling never have been evaluated at various exercise intensities. Methods and Results— Speckle tracking echocardiography was performed in 20 healthy sedentary subjects at rest and during a progressive submaximal exercise test at 20%, 30%, and 40% of maximal aerobic power. LV twist increased progressively with exercise intensity (10.5±3.2 to 15.8±4.5°; P <0.001), whereas longitudinal strain remained unchanged after the first workload, underlining the key role of torsional reserve in systolic-diastolic coupling during exercise. The increase in diastolic untwisting (−88.7±34.2 to −182.9±53.5 deg · s−1; P <0.01) was correlated to enhanced systolic twist ( R =0.61; P <0.001), and its magnitude of increase was significantly higher compared to diastolic longitudinal and circumferential strain rates (119±64% versus 65±44% and 57±24%, respectively), emphasizing its contribution to diastolic filling. The timing of peak untwisting and the chronology of diastolic mechanical events were unchanged during effort. Untwisting was driven mainly by apical rotation and determined mitral opening and isovolumic relaxation time ( R =0.47 and 0.61, respectively; P <0.001), whereas basal rotation and longitudinal and circumferential diastolic strain rates were major determinants of increased early diastolic filling ( R =0.64, 0.79, and 0.81, respectively; P <0.001). Conclusions— The use of speckle tracking echocardiography gives new insights into physiological adaptive LV mechanics during incremental exercise in healthy subjects, underlining the key role of torsional mechanics. It might be useful to better understand the mechanisms of diastolic dysfunction and exercise intolerance in various pathological conditions.

Subclinical Cardiac Abnormalities in Human Immunodeficiency Virus-Infected Men Receiving Antiretroviral Therapy

Although cardiotoxic effects of highly active antiretroviral therapy (HAART) are a growing concern, there is a lack of prospective studies of subclinical involvement of the heart in human immunodeficiency virus (HIV)-infected patients. This study evaluated noninvasively cardiac morphologic characteristics and function in HIV-positive (HIV(+)) men receiving HAART for > or =2 years with no clinical evidence of cardiovascular disease. Echocardiography at rest, including tissue Doppler imaging and exercise testing, were performed in 30 HIV(+) men (age 42.1 +/- 4.7 years, duration of HIV infection 10.4 +/- 4.7 years, duration of HAART 5.3 +/- 2.1 years) and 26 age-matched healthy controls. At rest, HIV(+) patients had similar left ventricular (LV) mass indexed to height(2.7) (40.6 +/- 9.5 vs 37.5 +/- 9.3 g/m; p >0.05), but a higher prevalence of LV diastolic dysfunction (abnormal relaxation or pseudonormal filling pattern in 64% of patients vs 12% of controls; p <0.001). LV systolic function indexes were significantly lower (ejection fraction 60.4 +/- 8.7% vs 66.9 +/- 6.9%; p <0.01, and tissue Doppler imaging peak systolic velocity 11.4 +/- 1.6 vs 13.5 +/- 2.2 cm/s; p <0.001). Pulmonary artery pressure was higher in patients compared with controls (32.1 +/- 5.4 vs 26.1 +/- 6.5 mm Hg; p <0.001). Exercise testing showed decreased exercise tolerance in HIV(+) patients, with no case of myocardial ischemia. In conclusion, subclinical cardiac abnormalities are frequently observed in HIV(+) patients on HAART. The usefulness of systematic noninvasive screening in this population should be considered. GECEM study no. 30: National Agency for AIDS Research (ANRS).

Doppler Echocardiography for the Estimation of Cardiac Output with Exercise

Insights into both normal and pathological cardiac responses to exercise have been hampered by lack of a safe, accurate, feasible means of estimating cardiac output (.Q) during high-intensity and maximal exercise. Doppler ultrasound noninvasively measures blood velocity as it exits the heart and can be performed during exhaustive exercise without interference of the subject or need for steady state. From the product of aortic blood velocity and cross-sectional area of the aorta, stroke volume (SV) can be calculated. Despite these advantages of the Doppler technique, a number of potential sources of error have raised concern regarding the accuracy of this method. These include transducer angulation, change in aortic cross-sectional area during exercise, turbulence and alteration of a flat velocity profile in the aorta with increased.Q, and uncertainties regarding the proper location for measurement of aortic outflow area.The magnitude of the influence of these potentially confounding variables on the accuracy of SV measurements determined by the Doppler technique is unknown. Estimates of both construct and concurrent validity suggest that the overall error may be small. Test-retest studies have indicated a high level of reliability with this technique.

Abnormal vascular reactivity at rest and exercise in obese boys

Background  Obese children exhibit vascular disorders at rest depending on their pubertal status, degree of obesity, and level of insulin resistance. However, data regarding their vascular function during exercise remain scarce. The aims of the present study were to evaluate vascular morphology and function at rest, and lower limb blood flow during exercise, in prepubertal boys with mild‐to‐moderate obesity and in lean controls.

Myostatin up-regulation is associated with the skeletal muscle response to hypoxic stimuli

Myostatin and hypoxia signalling pathways are able to induce skeletal muscle atrophy, but whether a relationship between these two pathways exists is currently unknown. Here, we tested the hypothesis that a potential mechanism for hypoxia effect on skeletal muscle may be through regulation of myostatin. We reported an induction of myostatin expression in muscles of rats exposed to chronic hypoxia. Interestingly, we also demonstrated increased skeletal muscle myostatin protein expression in skeletal muscle of hypoxemic patients with severe chronic obstructive pulmonary disease (COPD). Parallel studies in human skeletal muscle cell cultures showed that induction of myostatin expression in myotubes treated with hypoxia-mimicking agent such as cobalt chloride (CoCl(2)) is associated with myotube atrophy. Furthermore, we demonstrated that inhibition of myostatin by means of genetic deletion of myostatin or treatment with blocking antimyostatin antibodies inhibits the CoCl(2)-induced atrophy in muscle cells. Finally, addition of recombinant myostatin restored the CoCl(2)-induced atrophy in myostatin deficient myotubes. These results strongly suggest that myostatin can play an essential role in the adaptation of skeletal muscle to hypoxic environment.

Flow-mediated dilation and exercise-induced hyperaemia in highly trained athletes: comparison of the upper and lower limb vasculature

Aim:  The main purpose of the present study was to assess whether similar vascular adaptive changes could be obtained by long‐term intensive training involving predominantly either the lower or the upper limb musculature.

Carbon Monoxide Pollution Promotes Cardiac Remodeling and Ventricular Arrhythmia in Healthy Rats

RATIONALE Epidemiologic studies associate atmospheric carbon monoxide (CO) pollution with adverse cardiovascular outcomes and increased cardiac mortality risk. However, there is a lack of data regarding cellular mechanisms in healthy individuals. OBJECTIVES To investigate the chronic effects of environmentally relevant CO levels on cardiac function in a well-standardized healthy animal model. METHODS Wistar rats were exposed for 4 weeks to filtered air (CO < 1 ppm) or air enriched with CO (30 ppm with five peaks of 100 ppm per 24-h period), consistent with urban pollution. Myocardial function was assessed by echocardiography and analysis of surface ECG and in vitro by measuring the excitation-contraction coupling of single left ventricular cardiomyocytes. MEASUREMENTS AND MAIN RESULTS Chronic CO pollution promoted left ventricular interstitial and perivascular fibrosis, with no change in cardiomyocyte size, and had weak, yet significant, effects on in vivo cardiac function. However, both contraction and relaxation of single cardiomyocytes were markedly altered. Several changes occurred, including decreased Ca(2+) transient amplitude and Ca(2+) sensitivity of myofilaments and increased diastolic intracellular Ca(2+) subsequent to decreased SERCA-2a expression and impaired Ca(2+) reuptake. CO pollution increased the number of arrhythmic events. Hyperphosphorylation of Ca(2+)-handling and sarcomeric proteins, and reduced responses to beta-adrenergic challenge were obtained, suggestive of moderate CO-induced hyperadrenergic state. CONCLUSIONS Chronic CO exposure promotes a pathological phenotype of cardiomyocytes in the absence of underlying cardiomyopathy. The less severe phenotype in vivo suggests a role for compensatory mechanisms. Arrhythmia propensity may derive from intracellular Ca(2+) overload.

Metabolic Syndrome Individuals With and Without Type 2 Diabetes Mellitus Present Generalized Vascular Dysfunction Cross-Sectional Study

Objectives— The first objective of this study was to demonstrate differences within endothelial-dependent and endothelial-independent vasoreactivity in macro- and microcirculation beds among patients with metabolic syndrome (MetS) with and without type 2 diabetes mellitus (T2D) compared with healthy counterparts. The second objective was to determine relationships among the function of macro- and microvascular systems and abdominal adiposity, as well as inflammatory markers in the 3 groups. Approach and Results— Cross-sectional analyses of 53 patients with MetS without T2D and 25 with T2D, as well as aged 40 years and sex-matched healthy controls included microvascular (cutaneous blood flow measured with laser Doppler flowmetry in response to iontophoresis of acetylcholine and sodium nitroprusside), and macrovascular reactivity (flow-mediated dilation and nitrate-mediated dilation) along with anthropometric measures, plasma glucose, and insulin and inflammatory markers. Compared with controls, MetS participants showed depressed endothelial function of both micro- and macrocirculation beds. T2D in patients with MetS revealed an exacerbated vascular smooth muscle dysfunction in micro- and macrocirculation compared with MetS without T2D. Indices of micro- and macrocirculation were predominantly inversely related to abdominal fat and inflammatory markers. Conclusions— MetS was associated with endothelial-dependent and endothelial-independent dysfunction, affecting both the macro- and the microvascular systems. Participants with diabetes mellitus demonstrated the most severe smooth muscle dysfunction. The presence of central abdominal fat and systemic inflammation seems implicated in the pathogenesis of vascular dysfunctions in MetS.