Determinant Of Exercise-induced Changes Research Articles

Extent and predictors of exercise-induced changes in ischemic mitral regurgitation during handgrip exercise

Abstract Background Mitral regurgitation (MR) is frequent in patients with ischemic heart disease and carries a dismal prognosis. Recent studies suggest that ischemic MR is a dynamic condition influenced by global and regional left ventricular (LV) remodeling as well as mitral valvular deformation. Handgrip exercise may serve as alternative exercise intervention to bicycle exercise. Purpose To assess degree and determinants of exercise-induced changes in ischemic MR during handgrip exercise. Methods We prospectively enrolled 205 patients with at least mild ischemic MR that underwent echocardiography at rest and during three minutes of handgrip exercise according to a standardized protocol. Results Mean age in our patient cohort was 75±10 years, 30% were female, and 58% suffer from atrial fibrillation. Median NT-proBNP was 2657 (1331–6599) ng/l. Mean left ventricular ejection fraction was 44±14%. At rest, MR severity was graded as mild in 57% of patients, moderate MR in 34% and severe in 9%. Mean effective regurgitant orifice area (EROA) at rest was 15±6 mm2 and regurgitation volume was 25±11 ml. During handgrip exercise, 58 patients (28%) showed an increase in MR severity in at least one grade; 30 patients (15%) with non-severe MR at rest, developed severe MR during handgrip exercise. The EROA decreased (>5 mm2) in 5% of patients, remained unchanged in 50% (between −5 mm2 and +5 mm2), and increased (>5 mm2) in 45% of patients (Fig. 1B). A small increase (5–10 mm2) was observed in 30%, while 15% of patients revealed a marked increase in EROA (>10 mm2) (Fig. 1B). The degree of MR at rest was not associated with exercise-induced increases in EROA (r=−0.03; p=0.641)(Fig. 1C). However, echocardiographic parameters of local (e.g. tenting height) and global (e.g. LVESVi) LV remodeling, as well as mitral valvular deformation correlated with exercise-induced changes in EROA (Table 1). Conclusion In patients with secondary MR due to ischemic heart disease, handgrip echocardiography unmasks exercise-induced increases of MR severity in a significant proportion of patients. Dynamic MR during handgrip exercise is associated with parameters of global and local LV remodeling as well with parameters of mitral valvular deformation. Future studies need to address the prognostic importance of exercise-induced changes in MR severity in patients with ischemic cardiomyopathy. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): This work was supported by the Forschungskommission of the Medical Faculty of the Heinrich Heine University Düsseldorf to Maximilian Spieker for a Clinician Scientist Track.

Fitness level impacts salivary antimicrobial protein responses to a single bout of cycling exercise.

Salivary antimicrobial proteins (sAMPs) protect the upper respiratory tract (URTI) from invading microorganisms and have been linked with URTI infection risk in athletes. While high training volume is associated with increased URTI risk, it is not known if fitness affects the sAMP response to acute exercise. This study compared the sAMP responses to various exercising workloads of highly fit experienced cyclists with those who were less fit. Seventeen experienced cyclists (nine highly fit; eight less fit) completed three 30-min exercise trials at workloads corresponding to -5, +5 and +15 % of the individual blood lactate threshold. Saliva samples were collected pre- and post-exercise to determine the concentration and secretion of α-amylase, human neutrophil proteins 1-3 (HNP1-3) lactoferrin, LL-37, lysozyme, and salivary SIgA. The concentration and/or secretion of all sAMPs increased post-exercise, but only α-amylase was sensitive to exercise workload. Highly fit cyclists had lower baseline concentrations of α-amylase, HNP1-3, and lactoferrin, although secretion rates did not differ between the groups. Highly fit cyclists did, however, exhibit greater post-exercise increases in the concentration and/or secretion of a majority of measured sAMPs (percentage difference between highly fit and less fit in parentheses), including α-amylase concentration (+107 %) and secretion (+148 %), HNP1-3 concentration (+97 %) and secretion (+158 %), salivary SIgA concentration (+181 %), lactoferrin secretion (+209 %) and LL-37 secretion (+138 %). We show for the first time that fitness level is a major determinant of exercise-induced changes in sAMPs. This might be due to training-induced alterations in parasympathetic and sympathetic nervous system activation.

0112: Determinants and prognostic impact of left ventricular contractile reserve in asymptomatic aortic stenosis

The management of asymptomatic patients with severe aortic stenosis (AS) is extremely controversial. There are very few data regarding the assessment, determinants and prognostic value of left ventricular contractile reserve (LVCR) in these patients. We aimed to quantify LVCR and to evaluate its determinants and usefulness for risk stratification in asymptomatic patients with severe AS. Asymptomatic patients with severe AS (n=150, aortic valve area<1cm², 70±9 years, 64% of male) and preserved left ventricular (LV) systolic function (LV ejection fraction ≥55%) were prospectively referred to exercise stress echocardiography. Using 2D speckle tracking analysis, LVCR was defined as an exercise-induced changes in LV global longitudinal strain >2%. LVCR was present in 62 patients (41%) and there was no significant difference between LVCR and no LVCR groups regarding demographic, clinical and exercise data, as well as risk factors. Using multiple linear regression, after adjustment for age, sex and E/Ea ratio, the independent determinant of exercise-induced changes in LV global longitudinal strain were aortic mean pressure gradient (p=0.005), LV ejection fraction (p=0.035) and exercise indexed LA area (p=0.002). During a mean follow-up of 19±12 months, 76 events (51%) occurred. The absence of LVCR was associated with reduced 4-year cardiac event-free survival (26±6 vs. 53±11%, p<0.0001). By opposition, exercise-induced changes in LV ejection fraction did not predict the outcome (p=0.96). In multivariate analysis, the independent predictors of events were resting brain natriuretic peptide level (p<0.0001), aortic mean pressure gradient (p=0.037), exercise cardiac output (p=0.004) and absence of LVCR (HR=1.8, 95%CI: 1.05-3.08, p=0.033). In asymptomatic patients with severe AS, the main determinants of LVCR, as assessed using exercise-induced changes in LV global longitudinal strain, were related to AS severity and exercise LA size. The absence of LVCR is a powerful predictor of reduced cardiac event-free survival. These results strongly support the use of exercise stress echocardiography in asymptomatic AS.

Oral Abstract session: Stress echo in clinical practice: Friday 5 December 2014, 08:30-10:00 * Location: Agora

Oral Abstract session: Stress echo in clinical practice: Friday 5 December 2014, 08:30-10:00 * Location: Agora

Determinants of Exercise‐Induced Increase of Mitral Regurgitation in Patients with Acute Coronary Syndromes

Mechanisms behind exercise-induced increase of mitral regurgitation (MR) in patients with chronic ischemic heart disease have been described earlier. We describe the determinants of exercise-induced changes in MR in patients with non-ST-elevation acute coronary syndrome (NSTACS). Forty-five consecutive patients (mean + or - SD age 64 + or - 10 years, 37 men) with NSTACS underwent exercise echocardiography on a supine bicycle the day before angiography. The exercise was started with a load of 10 W with increments of 10 W every minute until symptoms developed or a max load of 100 W. Effective regurgitation orifice (ERO) was measured at rest and at peak exercise. Twelve patients had more than trace MR at rest with ERO 8 + or - 5 (mean + or - SD), range: 3-18 mm(2). In these patients, ERO increased during exercise to 13 + or - 6 (mean + or - SD), range: 6-23 mm(2) corresponding to an increase of 70% from rest (P = 0.001). Seven other patients developed new MR during exercise with ERO at peak exercise of 8 + or - 4 mm(2) (mean + or - SD), range: 4-14 mm(2). All these patients had significant increase in wall motion score index (WMSI) of 0.14 + or - 0.18 (mean + or - SD), P = 0.006, while in the 25 patients without MR at rest or during exercise, WMSI remained unchanged, -0.02 + or - 0.08 (mean + or - SD), P = 0.2. Exercise-induced increases of MR in patients with NSTACS are related to worsening of regional wall motions. (Echocardiography 2010;27:567-574).

175 Changes in Systolic Pulmonary Arterial Pressure during Exercise are Related to Changes in Mitral Regurgitation

Current guidelines recommend mitral surgery for asymptomatic patients with severe organic mitral regurgitation (OMR) and preserved LV systolic function when exercise pulmonary hypertension (PHT) is present. However, the determinants of exercise-induced PHT in such patients have not been evaluated. Resting and exercise transthoracic echocardiography were performed in 66 consecutive patients (61±15 years, 55% of male) with significant OMR. MR severity evaluated using effective regurgitant orifice (ERO) area. Systolic pulmonary arterial pressure (PAP) was derived from tricuspid regurgitation peak velocity and exercise PHT was defined as transtricuspid pressure gradient ≥50mmHg. Compared to patients with exercise PAP <50mmHg, those with exercise PHT (n=28, 42%) were significantly older. There was no significant difference between the 2 groups with regard to resting and exercise LV functions and to resting ERO. Nonetheless, patients with exercise PHT had higher exercise ERO (50±22 vs. 38±14mm 2 , p=0.03). The changes in ERO during exercise were significantly higher in patients with PHT (8±12 vs. -2±12mm 2 , p=0.004). Regarding to peak exercise PAP, the best correlations were found with age (r=0.39, p=0.007) and exercise ERO (r=0.47, p=0.0009). Moreover, changes in PAP during exercise were only correlated with the changes in ERO (r=0.50, p=0.0012). On multivariate analysis, after adjustment for age, sex and resting PAP, exercise-induced changes in ERO were independently associated with the changes in PAP (ERO: β=0.4, p=0.002). In addition, changes in MR severity were also independent predictors of exercise PHT (ERO: odds-ratio (OR) =1.2, 95%CI: 1.1-1.4, p=0.0008). Exercise PHT is frequent in patients with OMR. Changes in MR severity during exercise are the main determinants of exercise-induced changes in systolic PAP. Further studies are needed to evaluate whether changes in MR severity during exercise may have a prognostic impact in patients with OMR.

Impact of Changes in Myocardial Velocity Assessed by Tissue Doppler Imaging during Exercise on Dynamic Mitral Regurgitation in Patients with Nonischemic Cardiomyopathy

We evaluated the myocardial contractile reserve related to exercise-induced changes in functional mitral regurgitation (MR) by tissue Doppler imaging (TDI). Supine bicycle exercise was performed in 35 patients with nonischemic cardiomyopathy (age 51 +/- 12 years; EF < 40%) and resting, and peak exercise 2D echocardiographic parameters, and TDI data were obtained. V(avg) was defined as the average of peak systolic velocities of six basal LV segments by TDI. Myocardial contractile reserve, which was calculated by [peak exercise V(avg)- baseline V(avg)], was represented as DeltaV(avg). Dyssynchrony index was derived from the standard deviation of the time to the peak systolic velocity of 12 LV segments. During exercise (9.7 +/- 2.4 minutes), the mean V(avg) increased from 4.0 +/- 0.8 cm/s to 5.5 +/- 1.0 cm/s. The effective regurgitant orifice area (ERO) and the ratio of MR jet area to the left atrial area (JLA%) were 1.9 +/- 2.9 mm(2) and 12 +/- 12%, respectively. During exercise, ERO and JLA% significantly increased to 6.2 +/- 6.4 mm(2) and 21 +/- 13% (P < 0.05), respectively, with individually variable changes. Tenting area was found to be an independent factor that showed a relationship with the baseline severity of MR (r = 0.561, P < 0.001). Dyssynchrony index and DeltaV(avg) were found to correlate with both maximal MR severity at peak exercise and changes in MR during exercise. By multivariate analysis, DeltaV(avg) was found to be an independent determinant of exercise-induced changes in ERO (DeltaERO; r =-0.707, P< 0.001) and changes in JLA% (DeltaJLA%; r =-0.663, P< 0.001). In patients with nonischemic cardiomyopathy, impaired contractile reserve assessed by TDI velocity data may be an independent determinant affecting exercise-induced changes in dynamic MR.

Responses to acute exercise in type 2 diabetes, with an emphasis on metabolism and interaction with oral hypoglycemic agents and food intake

In people with type 1 diabetes mellitis (DM), insulin administration, food intake, and exercise have to be carefully matched to avoid either hypo- or hyperglycemia. People with type 2 DM have some insulin secretion, which changes with needs. Accordingly, during exercise, these people do not run the same metabolic risks as people with type 1 DM. However, a contraction-mediated increase in glucose clearance in muscle is intact in type 2 DM. Therefore, in the postabsorptive state in diet-treated type 2 DM, a marked reduction in hyperglycemia can occur during prolonged moderate exercise. Sulfonylurea drugs augment the rate of decline in plasma glucose, because stimulation of insulin secretion reduces hepatic glucose production. After abstention from sulfonylurea for 5 days, the rate of decrease in plasma glucose with exercise is also enhanced, but from a higher glucose level. In the postabsorptive state, brief vigourous exercise elicits an increase in plasma glucose concentration, reflecting an exaggerated counterregulatory hormone response and glucose production. Moreover, insulin sensitivity is reduced in the early postexercise period. In the postprandial state, both prolonged moderate exercise and intermittent high-intensity exercise markedly decrease meal-induced increases in glucose, insulin, and C-peptide concentrations, whereas glucose appearance in plasma is unchanged. When exercise bouts are isocaloric, responses are identical, indicating that overall energy expenditure, and not peak exercise intensity, is the major determinant of exercise-induced changes in overall glucose homeostasis and insulin secretion in type 2 DM. Neither prolonged moderate nor intermittent high-intensity exercise performed in the postprandial state influences glucose or insulin responses to a subsequent meal. Finally, in people with type 2 DM, after a high-fat meal, prolonged moderate exercise reduces the exaggerated increases in plasma concentrations of triglycerides contained in chylomicrons and very low-density lipoproteins.

Left ventricular dyssynchrony and dynamic functional mitral regurgitation: relationship or association?The opinions expressed in this article are not necessarily those of the Editors of the European Heart Journal or of the European Society of Cardiology.

Numerous parameters are associated with a dismal prognosis in heart failure patients. Some of these factors may be mechanistically related, such as increased left ventricular (LV) volume, functional mitral regurgitation (MR), QRS widening, and LV dyssynchrony. Indeed, LV dilation produces distortion of ventricular geometry. The apical and outward displacement of the mitral leaflets restricts their ability to close through tethering forces. QRS widening is frequently associated with LV dyssynchrony. Both dysfunction and dyssynchrony, notably the dyscoordination of the segments containing papillary muscles 1 reduce LV-generated mitral valve closing force. Functional MR varies dynamically depending on annular size, loading conditions, and a balance of closing force and mitral valvular deformation. Dynamic MR can be reliably quantitated during exercise testing. Large exerciseinduced increases in ischaemic MR are associated with acute pulmonary oedema 2 and a high risk of morbidity and mortality. 3 In patients with normal QRS duration but reduced LV contraction, exercise-induced changes in MR are not associated neither to the degree of MR at rest nor to the changes in global LV function, but are related to the changes in local LV distortion and in mitral deformation. 4 But are the determinants of exercise-induced changes in functional MR similar in patients with LV dyssynchrony? In other words, does the reduction in closing force play a more important role in this setting? Ennezat et al. 5 tested the hypothesis that myocardial dyssynchrony at baseline contributes to worsening of functional MR during exercise. They studied 70 heart failure patients; half of the population had ischaemic cardiomyopathy. Pulsed-wave Doppler tissue imaging was performed to assess and quantify LV dyssynchrony at rest. The proximal flow convergence technique was used to quantify MR both at rest and during exercise. Exercise-induced changes in MR were individually variable and were associated with the presence and the degree of LV dyssynchrony. The authors conclude that LV dyssynchrony at rest is related to worsening of functional MR during exercise in patients with systolic heart failure. Although functional MR and dyssynchrony are obviously continuous variables, cut-off values have been proposed for delineating their significance: effective regurgitant orifice (ERO) of functional MR � 20 mm 2 , exercise-induced increase 3 in MR � 13 mm 2 or LV dyssynchrony � 65 ms, defined as the maximum delay between peak systolic velocities among basal LV segments. 6 Using, for instance, this latter cut-off value for analysing Figure 2 in the article published by Ennezat et al., 5 we see that approximately half of their patients have no ‘significant’ LV dyssynchrony. In this subgroup, the absence of correlation between LV synchronicity and changes in mitral ERO is obvious; two-thirds of the patients exhibited a decrease in ERO during exercise and only one had a large (.13 mm 2 ) exercise-induced increase in MR. The correlation between the two parameters is apparent in the other half of the population who presented with significant LV dyssynchrony; no patient had a decrease in mitral ERO during exercise and seven (roughly 20% of this subgroup) developed a large exercise-induced increase in ERO. In the overall population, LV dyssynchrony at rest and exercise-induced changes in systolic mitral annular diameter were the two parameters independently associated with exercise-induced changes in functional MR. LV dyssynchrony was associated with changes in MR severity in patients with ischaemic and non-ischaemic cardiomyopathies. Exerciseinduced changes in annular diameter were related to changes in MR only in patients with non-ischaemic cardiomyopathy. The dynamic component of chronic functional MR, revealed by exercise testing has clinical implications. Some patients exhibit small changes in the amount of MR; others have a sizeable decrease in ERO mainly because of recruitable contraction of the basal LV segments. 4 These patients have a good long-term prognosis. 3 In contrast, a large rise in MR during exercise is associated with more frequent hospital admission for decompensated heart failure or flash pulmonary oedema. Repetitive acute exacerbation of functional MR accentuate left atrial and LV overload and

Determinants of Exercise-induced changes in mitral regurgitation in patients with coronary artery disease and left ventricular dysfunction

The objective of this research is to demonstrate the feasibility of sustained combustion in hybrid rocket motor configuration with oxidizers containing high concentrations of CO2, an in situ propellant suitable for Mars applications. Motor tests are performed by using N2O/CO2 mixtures as the oxidizer and paraffin fuel loaded with high concentrations metal powders. Fuel grains with aluminum and magnesium powders have been cast at 40% by mass in the paraffin wax binder. CO2 is mixed with liquid N2O up to 50% in weight percentage as a saturated liquid mixture. Experiments are performed in the blowdown mode using the self-pressurizing capability of the mixed oxidizers. A lab-scale hybrid motor with 70 mm grain length and 31 mm outer grain diameter is used to measure the key performance parameters such as regression rate and combustion efficiency. Successful ignition and sustained/stable combustion with the mixed oxidizer are achieved at CO2 concentrations up to 43% by mass in the liquid mixture. The primary conclusion from this study is that the operation of hybrid rockets with substantial levels of in situ propellant CO2 is feasible.

Determinants of exercise-induced changes in mitral regurgitation in patients with coronary artery disease and left ventricular dysfunction

ObjectivesWe sought to examine the determinants of exercise-induced changes in ischemic mitral regurgitation (MR) in patients with left ventricular (LV) dysfunction. BackgroundIn the post-myocardial infarction (MI) phase, ischemic MR contributes to worsening of symptoms and of LV dysfunction. MethodsIn this study, 70 patients in the chronic, post-MI phase, with LV ejection fraction <45% and at least mild MR, underwent semi-supine exercise Doppler echocardiography. The effective regurgitant orifice (ERO) of MR was quantified at rest and during exercise. Exercise-induced changes in ERO were compared with changes in mitral deformation and in local and global LV remodeling. ResultsThe wide range of exercise-induced ERO changes that were observed was unrelated to the degree of MR at rest (r = 0.20). Effective regurgitant orifice changes correlated best with changes in mitral deformation (i.e., differences in systolic mitral tenting area, systolic annular area, and coaptation height) (p < 0.0001). Posterior displacement of the papillary muscles was associated with larger changes in the ERO in both infarct groups. In patients with inferior MI, a decrease in the ERO was related to improvement in wall motion (r = 0.68). The independent predictors of ERO changes during exercise were changes in systolic annular area for all infarct categories, in tenting area and wall motion score in the global population and those with inferior infarction, and in apical displacement of mitral leaflets for patients with anterior MI. ConclusionsThe degree of MR at rest is unrelated to exercise-induced changes in EROs, which are related to those in local LV remodeling and in mitral deformation but not those in global LV function.

Are the reductions in triacylglycerol and insulin levels after exercise related?

Moderate exercise improves insulin sensitivity and reduces triacylglycerol (triglyceride; TG) concentrations. We hypothesized that changes in insulin sensitivity are an important determinant of exercise-induced changes in postprandial TG concentrations. Altogether, 38 men and 43 women, all of whom were normotriglyceridaemic and normoglycaemic, each underwent two oral fat tolerance tests with different pre-conditions: control (no exercise) and prior exercise (90 min of exercise at 60% of maximal O(2) uptake the day before). Venous blood samples were obtained in the fasting state and for 6 h after a high-fat mixed meal. In the control trial there were significant correlations between log fasting TG concentration and log fasting insulin concentration (r=0.42, P<0.0005) and between log postprandial TG response (area under the curve) and log postprandial insulin response (r=0.48, P<0.0005). Prior exercise reduced the fasting TG concentration by 18.2 +/- 2.2% (mean +/- S.E.M.) (P<0.0005), the postprandial TG response by 21.5 +/-1.9% (P<0.0005), the fasting insulin concentration by 3.8 +/- 3.1% (P<0.01) and the postprandial insulin response by 11.9 +/- 2.5% (P<0.0005). However, there was no relationship between the exercise-induced changes in log fasting TG and log fasting insulin (r=0.08, P=0.50), nor between the exercise-induced changes in log postprandial TG response and log postprandial insulin response (r=0.04, P=0.70). These data suggest that the reductions in fasting and postprandial TG levels elicited by a session of moderate-intensity exercise are not mediated by an increase in insulin sensitivity.

Circulating Insulin-Like Growth Factor I Mediates Exercise-Induced Increases in the Number of New Neurons in the Adult Hippocampus

Although the physiological significance of continued formation of new neurons in the adult mammalian brain is still uncertain, therapeutic strategies aimed to potentiate this process show great promise. Several external factors, including physical exercise, increase the number of new neurons in the adult hippocampus, but underlying mechanisms are not yet known. We recently found that exercise stimulates uptake of the neurotrophic factor insulin-like growth factor I (IGF-I) from the bloodstream into specific brain areas, including the hippocampus. In addition, IGF-I participates in the effects of exercise on hippocampal c-fos expression and mimics several other effects of exercise on brain function. Because subcutaneous administration of IGF-I to sedentary adult rats markedly increases the number of new neurons in the hippocampus, we hypothesized that exercise-induced brain uptake of blood-borne IGF-I could mediate the stimulatory effects of exercise on the adult hippocampus. Thus, we blocked the entrance of circulating IGF-I into the brain by subcutaneous infusion of a blocking IGF-I antiserum to rats undergoing exercise training. The resulting inhibition of brain uptake of IGF-I was paralleled by complete inhibition of exercise-induced increases in the number of new neurons in the hippocampus. Exercising rats receiving an infusion of nonblocking serum showed normal increases in the number of new hippocampal neurons after exercise. Thus, increased uptake of blood-borne IGF-I is necessary for the stimulatory effects of exercise on the number of new granule cells in the adult hippocampus. Taken together with previous results, we conclude that circulating IGF-I is an important determinant of exercise-induced changes in the adult brain.