Supine Bicycle Exercise Research Articles

The ramp and all-out exercise test to determine critical power: validity and robustness to manipulations in body position

PurposeThe purpose of the present study was to determine whether a contiguous ramp and all-out exercise test could accurately determine critical power (CP) in a single laboratory visit during both upright and supine cycle exercise.MethodsHealthy males completed maximal ramp-incremental exercise on a cycle ergometer in the upright (n = 15) and supine positions (n = 8), with task failure immediately followed by a 3-min all-out phase for determination of end-test power (EP). On separate days, participants undertook four constant-power tests in either the upright or supine positions with the limit of tolerance ranging from ~ 2 to 15 min for determination of CP.ResultsDuring upright exercise, EP was highly correlated with (R2 = 0.93, P < 0.001) and not different from CP (CP = 221 ± 40 W vs. EP = 226 ± 46 W, P = 0.085, 95% limits of agreement − 30, 19 W). During supine exercise, EP was also highly correlated with (R2 = 0.94, P < 0.001) and not different from CP (CP = 140 ± 42 W vs. EP = 136 ± 40 W, P = 0.293, 95% limits of agreement − 16, 24 W).ConclusionThe present data suggest that EP derived from a contiguous ramp all-out exercise test is not different from the gold-standard method of CP determination during both upright and supine cycle exercise when assessed at the group level. However, the wide limits of agreement observed within the present study suggest that EP and CP should not be used interchangeably.

Spleen Contraction During Step‐Transition Supine Cycling Exercise: Preliminary findings

The current literature suggests that the spleen plays a significant role during physiological stress like exercise or apnea, primarily due to its capacity to contract and release additional red blood cells (RBC) into the systemic circulation. Besides the RBC release, human spleen emptying is also associated with circulating platelets release. However, data on the circulating platelets release following acute exercise have not yet been examined thoroughly. This is especially important since the spleen platelet volume is ~20% larger compared to the volume of circulating platelets, and some authors suggest that increased spleen platelet concentration is associated with the greater risk of a cardiovascular or cerebrovascular event during exercise. The present study aims to explore the magnitude of spleen contraction during on-transient supine cycling exercise in healthy humans. We hypothesized that the spleen is capable of rapid contractions during on-transient cycling, thereby releasing an additional amount of both RBC and platelets into the systemic circulation. Such an increase in RBC count in particular may facilitate O2 transport, and result in faster oxygen kinetics during on transient supine cycling. Healthy, active volunteers (age= 22±3, V̇O2 max.= 48±5 mL·kg·min-1), completed three laboratory visits, including a detailed medical examination, resting ultrasound imaging of the spleen, V̇O2 max. test until voluntary exhaustion, and a supine step-transition test from 20 W to a moderate-intensity cycling power output (PO), corresponding to V̇O2 at 90% gas exchange threshold (GET). During the step-transitions breath-by-breath pulmonary oxygen uptake (V̇O2p), near-infrared spectroscopy derived muscle oxygenation, and beat-by-beat cardiovascular response (via Finapres) were continuously monitored. In parallel, minute by minute ultrasonic measurements of the spleen function were performed in successive, 3 sec. time frames. Blood samples were drawn from the antecubital vein before and immediately after the acute exercise intervention.Currently, six participants completed all study procedures. Compared to baseline readings, the largest spleen volume reduction (~40%) was observed during the 6th minute of cycling at 90% GET. Spleen volume recovered to baseline values after 20 minutes. Immediately after exercise cessation the mean RBC and platelet count increased significantly by 3.2% and 6.5%, respectively. In parallel, the V̇O2p was 46±10 sec, while the mean V̇O2 uptake was ~2.5 L·min-1. Secondary to these findings, transient rises in mean arterial pressure (MAP) and heart rate (HR), were observed during the step-transition exercise, with MAP and HR reaching the highest value of 110±4 mmHg and 149±2 bmp, respectively. In conclusion, these preliminary findings indicate that splenic contraction evoked by a series of on-transient cycling bouts at 90% GET results in a rapid increase in RBC and platelet count into the systemic circulation of healthy active individuals.

Levosimendan Improves Hemodynamics and Exercise Tolerance in PH-HFpEF: Results of the Randomized Placebo-Controlled HELP Trial

ObjectivesThe purpose of this study was to evaluate the effects of intravenous levosimendan on hemodynamics and 6-min walk distance (6MWD) in patients with pulmonary hypertension and heart failure with preserved ejection fraction (PH-HFpEF). BackgroundThere are no proven effective treatments for patients with PH-HFpEF. MethodsPatients with mean pulmonary artery pressure (mPAP) ≥35 mm Hg, pulmonary capillary wedge pressure (PCWP) ≥20 mm Hg, and LVEF ≥40% underwent 6MWD and hemodynamic measurements at rest, during passive leg raise, and supine cycle exercise at baseline and after an open-label 24-h levosimendan infusion (0.1 μg/kg/min). Hemodynamic responders (those with ≥4 mm Hg reduction of exercise-PCWP) were randomized (double blind) to weekly levosimendan infusion (0.075 to 0.1 ug/kg/min for 24 h) or placebo for 5 additional weeks. The primary end point was exercise-PCWP, and key secondary end points included 6MWD and PCWP measured across all exercise stages. ResultsThirty-seven of 44 patients (84%) met responder criteria and were randomized to levosimendan (n = 18) or placebo (n = 19). Participants were 69 ± 9 years of age, 61% female, and with resting mPAP 41.0 ± 9.3 mm Hg and exercise-PCWP 36.8 ± 11.3 mm Hg. Compared with placebo, levosimendan did not significantly reduce the primary end point of exercise-PCWP at 6 weeks (−1.4 mm Hg; 95% confidence interval [CI]: −7.8 to 4.8; p = 0.65). However, levosimendan reduced PCWP measured across all exercise stages (−3.9 ± 2.0 mm Hg; p = 0.047). Levosimendan treatment resulted in a 29.3 m (95% CI: 2.5 to 56.1; p = 0.033) improvement in 6MWD compared with placebo. ConclusionsSix weeks of once-weekly levosimendan infusion did not affect exercise-PCWP but did reduce PCWP incorporating data from rest and exercise, in tandem with increased 6MWD. Further study of levosimendan is warranted as a therapeutic option for PH-HFpEF. (Hemodynamic Evaluation of Levosimendan in Patients With PH-HFpEF [HELP]; NCT03541603)

Supine Cycling Exercise Enhances Cerebral Oxygenation of Motor-Related Areas in Healthy Male Volunteers.

It has been reported that the cardiovascular response in the supine position is different from that in the sitting position. However, there are few reports on the effects of posture on cerebral oxygenationduring exercise. Cycling exercises change oxygenated hemoglobin (O2Hb) and deoxygenated hemoglobin (HHb) levels in motor-related areas. Therefore, this study compared O2Hb levels at motor-related areas during recumbent versus supine cycling. Eleven healthy young maleperformed a 30-min cycling exercise protocol at 50% of the maximal oxygen uptake (VO2 max) in the recumbent and supine positions. Near-infrared spectroscopy (NIRS) was used to measure exercise-induced O2Hb and HHb changes in the right (R-PMA) and left premotor areas (L-PMA), supplementary motor area (SMA), and primary motor cortex (M1). In R-PMA, L-PMA and SMA, the O2Hb obtained during supine cycling was significantly higher than that during recumbent cycling (R-PMA, 0.031±0.01 vs. 0.693±0.01; L-PMA, 0.027±0.01 vs. 0.085±0.013; SMA, 0.041±0.011 vs. 0.076±0.008mM·cm, recumbent vs. supine position; p<0.05). These results suggest that supine cycling exercise increases R-PMA, L-PMA, and SMA O2Hb levels in healthy youngmen.

Left ventricular outflow obstruction occurs immediately after exercise in patients with non-obstructive hypertrophic cardiomyopathy

We evaluated the hemodynamic and geometric determinants of latent obstruction (LO, trans-left ventricular outflow tract (LVOT) gradient ≥30 mmHg with provocation) in patients with non-obstructive hypertrophic cardiomyopathy (HCMP). A total of 35 patients with non-obstructive HCMP underwent stepwise supine bicycle exercise echocardiography. Trans-LVOT pressure gradients, mitral geometric parameters, left ventricular ejection fractions (LVEF) and left ventricular end-systolic and diastolic dimensions (LVESD, LVEDD) were measured at each stage. The highest peak LVOT pressure gradient predominantly occurred immediately after exercise (n = 32, 91.3%) rather than during peak exercise (n = 3, 8.7%). Significant LO developed in nine patients (25%). No significant differences were found in resting echocardiographic parameters. Compared to the remaining patients, however, patients with LO had longer residual mitral leaflets (defined as residual portions of leaflets after coaptation; 4 ± 4 vs. 13 ± 4 mm, respectively; p = 0.001) and higher resting LVOT pressure gradients (7.4 ± 3.7 vs. 12.9 ± 5.8 mmHg, respectively; p = 0.001). Substantial decreases in mitral annular diameters from peak exercise to recovery after exercise were observed in the LO group, while mitral annular diameters increased after exercise in the non-LO group. In conclusion, the highest peak LVOT pressure gradient predominantly occurred immediately after exercise rather than during peak exercise, regardless of LO. Abrupt decrease of mitral annular diameter immediately after exercise, a longer residual mitral leaflet and a higher resting LVOT pressure gradient at rest might be related to LO.

Exercise physiology of the left atrium: quantity and timing of contribution to cardiac output.

Although the phases of left atrial (LA) function at rest have been studied, the physiological response of the LA to exercise is undefined. This study defines the exercise behavior of the normal left atrium by quantitating its volumetric response to graded effort. Healthy subjects (n = 131) were enrolled from the Health eHeart cohort. Echocardiograms were obtained at baseline and during ramped supine bicycle exercise. Left ventricular volume index, stroke volume index (LVSVI), left atrial end-systolic volume index (LAESVI), left atrial end-diastolic volume index (LAEDVI), and left atrial emptying fraction (LAEF), reservoir fraction, and conduit fraction were analyzed. The LVSVI increased with low exercise but did not increase further with peak exercise; cardiac output increased through the agency of heart rate. The LAESVI and LAEDVI decreased and the LAEF increased with exercise. As a result, the LA reservoir volume index was static throughout exercise. The reservoir fraction decreased from 46% at rest to 40% with low exercise (P < 0.001) in association with increased LVSVI and remained similar at peak exercise. The conduit volume index increased from 20 mL/m2 at rest to 24 mL/m2 at low exercise and stayed the same at peak exercise. Similarly, the conduit fraction increased from 54% at rest to 60% at low exercise (P < 0.001) and did not change further with peak exercise. Although atrial function increased with exercise, the major contribution to the augmentation of LV stroke volume is LA conduit fraction, a marker of active ventricular relaxation. Furthermore, the major determinant of raising cardiac output during high-level exercise is heart rate.NEW & NOTEWORTHY Diseases of the left atrium (LA) are major sources of disability (e.g., strokes and fatigue), but its exercise physiology has been unstudied. Such knowledge may allow early recognition of disease and suggest therapies. We show that in normal subjects, low-level exercise decreases LA volume and increases its ejection fraction. However, these changes offset each other volumetrically, and the contribution to LV filling from a full to an empty LA (reservoir function) is static. Higher levels of exercise do not change LA reservoir contribution. Blood flowing directly from the pulmonary vein to LV (conduit flow) impelled by augmented LV active relaxation (suction) is the major source of a modest increase in LV stroke volume. The major source of increased cardiac output with exercise is heart rate. During all stages of exercise, the LA works hard but only to keep up. We believe that our findings provide an additional set of benchmarks through which to quantitate LA pathology and gauge its progression.

Levosimendan Improves Hemodynamics And Submaximal Exercise Capacity In Ph-hfpef: Primary Results From The Help-ph-hfpef Multicenter Randomized Controlled Trial

Introduction There is currently no effective treatment for patients with HFpEF and pulmonary hypertension (PH-HFpEF). We hypothesized that levosimendan (LEVO), a calcium sensitizer with inotropic and vascular smooth muscle relaxant properties, would improve hemodynamics and exercise capacity in PH-HFpEF. Methods We conducted a multicenter, double-blind, placebo-controlled trial testing the effects of once-weekly IV LEVO on hemodynamics and 6 minute walk distance (6MWD) in patients with PH-HFpEF. Participants with mean pulmonary artery (mPAP) ≥35 mmHg, PCWP ≥20 mmHg, LVEF ≥40% and NYHA II-III symptoms underwent 6MW and invasive hemodynamic assessments at rest, passive leg raise (PLR) and supine cycle exercise (EX) at baseline and following a 24-hour infusion of LEVO (0.1 μg/kg/min). Hemodynamic responders, defined as those with ≥4 mmHg reduction of EX PCWP, were then randomized, double blind, to a once weekly infusion of LEVO (up to 0.1 μg/kg/min) or placebo for 6 weeks, at which point hemodynamic assessments and 6MW test were repeated. The primary endpoint was between-group difference in the change of EX PCWP. Results Of 44 subjects enrolled, 37 (84%) qualified as responders and were randomized to LEVO (n=18) or placebo (n=19). Patients (69±9 years old, 61% women) displayed severe combined pre- and post-capillary PH at baseline (resting mPAP 41±10, PCWP 25±6 mmHg pulmonary vascular resistance 3.4±2.7). At 6-weeks, LEVO had no significant effect on EX PCWP compared to placebo (-1.4 mmHg, 95% CI, -7.7 to 4.8, p=0.65). However, in a mixed-effect repeated measure regression analysis incorporating rest, PLR, and EX stages, LEVO reduced PCWP by 3.9±2.0 mmHg as compared to placebo (p=0.047, Figure). As compared to placebo, LEVO improved 6MWD by 29 m (95% CI, 3 to 56, p=0.033). LEVO was well-tolerated with no difference in the incidence of adverse events compared to placebo. Conclusions In patients with PH-HFpEF, once-weekly treatment with LEVO for 6 weeks reduced PCWP and increased 6MWD without adverse effects. A phase 3 study to definitively test the safety and efficacy of LEVO as a treatment for PH-HFpEF is warranted.

Abstract 15294: 24-hour Levosimendan Infusion Decreases Biventricular Filling Pressures and Increases Cardiac Output at Rest and Exercise in PH-HFpEF

Background: There are no specific treatments for patients with HFpEF and pulmonary hypertension (PH-HFpEF). Increased central and pulmonary venous pressures (CVP, PCWP) are believed to contribute importantly to symptoms at rest and during exercise. Levosimendan (LEVO), a calcium sensitizer/KATP channel activator, is known to reduce CVP and PCWP in patients with reduced LVEF. We hypothesized that LEVO would have similar effects in PH-HFpEF. Methods: 44 PH-HFpEF patients with mean pulmonary artery (mPAP) ≥35 mmHg, PCWP ≥20 mmHg, LVEF ≥40% and NYHA II or III symptoms underwent hemodynamic measurements at rest, during passive leg raise (PLR) and during supine bicycle exercise for 3 minutes at 25 Watts (EX) at baseline and following a continuous 24-hour infusion of LEVO (0.1 μg/kg/min) as part of a multicenter clinical trial. Measurements included CVP, mPAP, PCWP, mean arterial pressure (MAP) and cardiac index (CI); pulmonary and systemic vascular resistances (PVR, SVR) were calculated. Hemodynamic tracings were analyzed in a core lab blinded to condition and timepoint. The primary endpoint was the change of PCWP at 25 Watts. Results: Patients averaged 69±9.1 years old, 61.4% were female and had a mPAP of 41.0±9.3 mmHg at rest. LEVO decreased mPAP at rest, CVP and PCWP at rest and EX, and increased CI with EX; there were no significant changes in mPAP, PVR or SVR. Resting and EX hemodynamic data are summarized in the Table. 37 of the 44 patients (84%) were considered hemodynamic “responders” based on a pre-specified ≥4 mmHg decrease of EX PCWP. Conclusions: In patients with PH-HFpEF, a 24 hour levosimendan infusion at 0.1 μg/kg/min decreased CVP and PCWP and increased CI at rest and EX, despite no significant effect on SVR or PVR. A majority of patients exhibited acute hemodynamic response. While the underlying mechanism(s) remain to be clarified, LEVO’s effects on CVP and PCWP warrant further study of this drug as a treatment for PH-HFpEF.

Hyperventilation echocardiography in INOCA: the HEROIC study

Abstract Background Patients with ischemia and no obstructive coronary artery disease (INOCA) are a heterogeneous group and an unmet diagnostic challenge. Noninvasive Doppler is a feasible tool to assess coronary flow velocity (CFV) in left anterior descending coronary artery (LAD) during stress echocardiography (SE). Aim To assess CFV response during coronary vasoconstrictor and vasodilator stimuli in INOCA patients. Methods In a prospective single center study, we enrolled 16 INOCA patients (age 60±12 years, 15 females) with previously normal angiograms. All underwent SE testing with hyperventilation (HYP, respiratory rate of 30 per min for 5') followed by supine bicycle exercise (HYP+EXE); and adenosine CFV evaluation (ADO, 0.84 mg/kg in 1 min) on the other day. The ratio of peak/rest changes of CFV during HYP in LAD was taken as an index of vasoconstriction, and CFV reserve was evaluated after EXE. An abnormal response to HYP was a CFV ratio &amp;lt;1.0 (vasoconstrictor response). An abnormal response to ADO was a CFV reserve &amp;lt;2.0 (blunted vasodilatory response). CFVR at peak HYP+ EXE was an indicator of endothelial dependent vasodilatation. Results The double product increased during HYP, in comparison to rest (13 337 vs 9858, p&amp;lt;0.001), and further increase with EXE (21 118 vs HYP, p&amp;lt;0.001). Chest pain or dyspnea were present in 2/16 pts during HYP, and in 5/16 patients during HYP+EXE (12.5% vs 31.25%, p=0.083). ST segment depression (≥1mm) was present in 1/16 patients during HYP, and 3/16 during HYP+EXE. Two patients showed regional wall motion abnormalities with HYP+EXE. CFVR response was blunted in 9/16 patients during HYP+EXE, and abnormal for vasoconstriction during HYP in 6. Vasodilation during ADO was preserved in all patients. There was significant difference between CFVR response during HYP+EXE and ADO (1.9±0.5 vs 2.4±0.4 respectively, p=0.039), and between CFVR HYP and ADO (1.2±0.3 vs 2.4±0.4, p&amp;lt;0.001). Conclusion In INOCA patients, HYP+EXE is a more powerful ischemic stress than HYP alone and unmasks abnormalities in regional wall motion and/or CFV response in over one- half of patients, likely unmasking the underlying abnormal coronary vasomotor response of large epicardial and/ or small coronary vessels. INOCA patients show profound heterogeneity of coronary vasomotor responses which can be detected with a combined vasodilator - vasoconstrictor SE approach with CFV assessment. The clarification of underlying coronary microcirculatory heterogeneity is the prerequisite for a personalized treatment, and can be easily extracted from CFV-SE. Normal INOCA hearts are all alike, every abnormal heart is abnormal in its own way. Funding Acknowledgement Type of funding source: None

Comparison of Outcomes in Adults With Ventricular Septal Defect Closed Earlier in Life Versus Those in Whom the Defect Was Never Closed

Ventricular septal defects (VSDs) have recently demonstrated poorer functional outcome with disrupted ventricular contractility during exercise in young patients. It is not known whether this will change with age. Therefore, echocardiography was performed in older patients with congenital VSDs, either surgically closed or unrepaired and all without Eisenmenger physiology, to compare functional outcomes with healthy peers. Transthoracic echocardiography was performed at rest and during supine bicycle exercise, with tissue velocity Doppler for assessment of primary end points: isovolumetric acceleration and systolic velocities. In total, 30 surgically closed VSDs (51 ± 8 years) with 30 healthy controls (52 ± 9 years) and 30 unrepaired VSDs (55 ± 12 years) with 30 matched controls (55 ± 10 years) were included. Surgical patients displayed lower right ventricular (RV) systolic and early diastolic-filling velocities compared with controls, p <0.01, lower tricuspid annular plane systolic excursion (17.8 ± 5 vs 22.7 ± 3mm, p <0.01) and lower fractional area change (37.8 ± 6 vs 46.4% ± 7%, p <0.01). Unrepaired VSDs also had lower RV fractional area change than matched controls (39.9 ± 7 vs 48.4% ± 7%, p <0.01). Both patient groups had more tricuspid regurgitation and larger RV outflow tract dimensions than controls, p <0.01. During exercise, isovolumetric acceleration and systolic velocities were lower in both patient groups compared with controls, with the difference increasing with workload level. In conclusion, adults in their mid-50s with surgically closed or unrepaired VSDs have abnormal RV function at rest, with even more pronounced differences during exercise. These results suggest that a VSD, whether repaired early or considered hemodynamically insignificant, is not a benign lesion and continuous follow-up of adults is warranted.

Influence Of Priming Exercise On Muscle Deoxygenation Kinetics During Upright And Supine Cycle Exercise

A bout of prior heavy “priming” exercise typically reduces the time constant of fundamental phase oxygen uptake (VO2) kinetics (τVO2) in the supine position, an effect that is generally absent during upright exercise. This priming-induced speeding of pulmonary VO2 kinetics has been attributed to increased muscle oxygenation at the onset of the second bout. However, the extent to which priming-induced improvements in muscle oxy/deoxygenation status differ across distinct muscle regions, as well as between deep vs. superficial muscle and with respect to body position, remains unknown. PURPOSE: To examine the impact of priming exercise on pulmonary VO2 and muscle deoxygenation kinetics at three muscle sites (superficial rectus femoris [RFs], deep [VLd] and superficial [VLs] vastus lateralis) using time-resolved near-infrared spectroscopy during upright (U) and supine (S) exercise. METHODS: 7 healthy men completed an incremental ramp test to determine VO2 max and the gas exchange threshold in S. 4 visits followed whereby participants performed two 6-min bouts of heavy exercise separated by 6-min unloaded pedalling in two conditions: 1) during constant power exercise at 40%Δ in S; and 2) during exercise at the same absolute work rate in U. Pulmonary VO2 and muscle deoxy[heme] kinetics were determined during each test. RESULTS: τVO2 was reduced in bout 2 in S (bout 1: 42 ± 12 vs. bout 2: 31 ± 7 s, P = 0.016) but not in U (bout 1: 32 ± 9 vs. bout 2: 28 ± 5 s, P = 0.32). The fundamental phase τdeoxy[heme] was greater in bout 2 for RFs in both postures (S, bout 1: 20 ± 7 vs. bout 2: 31 ± 18 s; U, 1: 11 ± 3 vs. bout 2: 23 ± 9 s, P = 0.021), whereas it was increased in bout 2 for VLs during U only (bout 1: 10 ± 3 vs. bout 2: 15 ± 4 s, P = 0.028). The fundamental phase muscle deoxy[heme] amplitude was greater in bout 2 for RFs (P = 0.001) and VLs (P = 0.024) in both U and S. Both the fundamental phase τdeoxy[heme] and amplitude did not differ between bouts 1 and 2 for VLd in either position (both P > 0.05). CONCLUSION: Prior heavy exercise reduced τVO2 in S but not U. This was accompanied by a greater amplitude and slower rate of muscle deoxygenation in superficial but not deep muscle. The contrasting responses of deep and superficial muscle to priming exercise in both U and S suggests that these muscles rely on fundamentally different O2 transport strategies.

Relationship Between Lung Diffusion And Exercise Capacity In Heart Failure With Preserved Ejection Fraction

PURPOSE: Patients with heart failure with preserved ejection fraction (HFpEF) have impaired lung diffusion (DL) at rest and during exercise which may contribute to a reduced exercise capacity. However, it is unclear whether these impairments are solely due to alterations in pulmonary hemodynamics or related to other cardiopulmonary factors which may impair oxygen uptake such as the inability to recruit lung surface area. Therefore this study examined simultaneous measurements of DL for carbon monoxide (DLCO) and nitric oxide (DLNO), which allows for partitioning of DL into its alveolar-capillary membrane (Dm) and pulmonary capillary blood volume (Vc) components, to better understand the relationship between exertional changes in lung diffusion and exercise capacity. METHODS: HFpEF patients (N=17, age=62±9y, BMI=36±8kg/m2) undergoing exercise right heart catheterization performed simultaneous rebreathe DLCO/NO tests at rest and during each stage of incremental supine cycling exercise, and membrane conductance (Dm) and pulmonary capillary blood volume (Vc) were calculated. Breath-by-breath pulmonary gas exchange was recorded throughout rest and exercise. RESULTS: All patients were hemodynamically diagnosed with HFpEF (pulmonary capillary wedge pressure >15 at rest and/or >25 mmHg during exercise). Overall lung and alveolar-capillary membrane diffusion increased from rest to peak exercise (DLCO: 11.8±4.0 to 16.2±7.4 ml/min/mmHg, DLNO: 33.1±11.5 to 48.4±21.9 ml/min/mmHg, Dm: 18.9±7.2 to 28.3±13.1 ml/min/mmHg; p’s<0.01). The change in DL was related to exercise capacity (change in DLCO vs. peak VO2: R=0.69, p<0.01, change in DLNO vs. peak VO2: R=0.65, p<0.01) and this was primarily driven by changes in Dm (change in Dm vs. peak VO2: R=0.63, p<0.01) but not Vc (change in Vc vs. peak VO2: R=0.15, p=0.582). CONCLUSIONS: These data highlight that a limited increase in lung diffusion and alveolar-capillary membrane conductance during exercise are associated with a lower VO2 peak in HFpEF patients. In addition to hemodynamic constraints previously reported in HFpEF, an inability to recruit lung surface area during exercise may also contribute to the reduced exercise capacity in these patients.

Optimal Use of Vasodilators for Diagnosis of Microvascular Angina in the Cardiac Catheterization Laboratory

Background:Among patients with angina and nonobstructive coronary artery disease, those with coronary microvascular dysfunction have a poor outcome. Coronary microvascular dysfunction is usually diagnosed by assessing flow reserve with an endothelium-independent vasodilator like adenosine, but the optimal diagnostic threshold is unclear. Furthermore, the incremental value of testing endothelial function has never been assessed before. We sought to determine what pharmacological thresholds correspond to exercise pathophysiology and myocardial ischemia in patients with coronary microvascular dysfunction.Methods:Patients with angina and nonobstructive coronary artery disease underwent simultaneous acquisition of coronary pressure and flow during rest, supine bicycle exercise, and pharmacological vasodilatation with adenosine and acetylcholine. Adenosine and acetylcholine coronary flow reserve were calculated as vasodilator/resting coronary blood flow (CFR and AchFR, respectively). Coronary wave intensity analysis was used to quantify the proportion of accelerating wave energy; a normal exercise response was defined as an increase in accelerating wave energy from rest to peak exercise. Ischemia was assessed by quantitative 3-Tesla stress perfusion cardiac magnetic resonance imaging and dichotomously defined by a hyperemic endo-epicardial gradient <1.0.Results:Ninety patients were enrolled (58±10 years, 77% female). Area under the curve using receiver-operating characteristic analysis demonstrated optimal CFR and AchFR thresholds for identifying exercise pathophysiology and ischemia as 2.6 and 1.5, with positive and negative predictive values of 91% and 86%, respectively. Fifty-eight percent had an abnormal CFR (of which 96% also had an abnormal AchFR). Of those with a normal CFR, 53% had an abnormal AchFR, and 47% had a normal AchFR; ischemia rates were 83%, 63%, and 14%, respectively.Conclusions:The optimal CFR and AchFR diagnostic thresholds are 2.6 and 1.5, with high-positive and negative predictive values, respectively. A normal CFR value should prompt the measurement of AchFR. A stepwise algorithm incorporating both vasodilators can accurately identify an ischemic cause in patients with nonobstructive coronary artery disease.

Exercise behavior of degenerative mitral stenosis.

Mitral annular calcification (MAC) is increasingly encountered, particularly among the elderly and those with chronic kidney disease, and is often associated with a transvalvular gradient. In contrast to rheumatic mitral stenosis relatively little is known about mitral stenosis due to MAC. We aimed to clarify whether exercise limitation in this group is primarily due to valvular obstruction or ventricular dysfunction resulting from multiple comorbidities. 20 patients with severe MAC (bulky calcium deposits which restricted leaflet motion) were submitted to supine bicycle exercise, measuring Doppler and echocardiographic parameters at baseline and during exercise. They were compared 1:1 to subjects matched for age, sex, and left ventricular wall thickness. At baseline MAC subjects had higher mean mitral valve gradients (MVG) than comparison subjects (7.5 ± 3.8 vs 1.6 ± 0.8mm Hg, p < 0.0001), along with larger indexed left atrial volumes (54.4 ± 14.9 vs 34.0 ± 11.7mL, p < 0.0001) and reduced left atrial strains (reservoir, conduit, and booster pump). With exercise MAC subjects reached higher levels of MVG (17.3 ± 8.4 vs 5.5 ± 2.5mm Hg, p < 0.0001), and pulmonary artery systolic pressure (estimated from tricuspid regurgitant jet [TR] velocity) and displayed a moderate correlation between ΔMVG and ΔTR velocity (r2 = 0.57). MAC subjects whose exercise MVG was ≥ 15mm Hg all had a peak pulmonary artery systolic pressure > 60mm Hg. MAC subjects also had relative chronotropic incompetence. Patients with severe MAC and a transvalvular gradient experience large increases in MVG and pulmonary pressure with exercise, similar to what has been described in rheumatic mitral stenosis. MAC may be an under-recognized cause of dyspnea and exercise intolerance in older patients.

Reduced Exercise Capacity in Diabetes Mellitus Is Not Associated with Impaired Deformation or Twist

Exercise capacity is frequently reduced in people with diabetes mellitus (DM) and may be due to subclinical cardiac dysfunction. Speckle-tracking echocardiography is now widely available; however, the clinical utility and significance of left ventricular (LV) strain and twist parameters remain uncertain. We hypothesized that LV strain and twist would be reduced in DM subjects during exercise. Adults with type 1 or type 2 DM and age- and sex-matched controls performed cardiopulmonary exercise testing (VO2 peak) and supine bicycle exercise echocardiography. Detailed echocardiographic assessment of biventricular function was performed at baseline and repeated during incremental exercise to maximal intensity. Of the 60 participants completing the study protocol, 51 (34 DM, 17 controls; mean age, 42±13years; 69% male; DM duration, 16±10years) had sufficient image quality to assess LV deformation and twist mechanics at rest. Of these, 38 (25 DM, 13 controls) were able to be assessed immediately after exercise. Baseline LV systolic and diastolic function using standard echocardiography measurements were similar between groups. Resting LV global longitudinal strain, twist, twist rate and untwist rate, and the corresponding peak exercise and reserve measures did not differ significantly. As compared with the control subjects, exercise capacity was reduced in the DM cohort (VO2 peak 33±10 vs 41±12mL/minute/kg; P=.02); however, no correlation was observed between VO2 peak and LV twist reserve (R=0.28, P=.09), LV twist rate reserve (R=0.14, P=.39), or LV untwist rate reserve (R=0.24, P=.14). Despite reduced VO2 peak, LV twist mechanics at rest and after maximal intensity exercise did not differ significantly in a cohort of asymptomatic DM subjects with normal resting LV systolic and diastolic function compared with age- and sex-matched controls. This would suggest that exercise capacity can be reduced in the absence of subclinical cardiac dysfunction and that noncardiac factors should be considered as alternative explanations.

P1398 Echocardiographic continuous monitoring of exercise stress test using probe fixation device

Abstract Background Stress echocardiography (SE) plays an important role among methods of noninvasive diagnosis of ischemic disease. Despite the advantages of physical exercise as the most physiologic stressor, it is difficult (bicycle ergometer) or impossible (treadmill) to obtain and maintain the acoustic window during the exercise. Recently, an innovative probe fixation device was introduced and a research plan was developed to assess the feasibility of external probe fixation during exercise echocardiography on a supine bicycle and upright treadmill exercise for the first time. Methods 37 subjects (36 men, mean age 39 ± 16 years, 21 healthy volunteers, 16 patients with suspected coronary artery disease) were included in this study. This preliminary testing stage included mostly men due to more problematic probe fixation in women. All subjects underwent a submaximal exercise stress test on a treadmill (17/37) or bicycle ergometer (11/37). Both sector and matrix probes were used. We assessed semi-quantitatively the quality of acquired apical views at each stage – the four-point grading system was used (0-no view, 1-suboptimal quality, 2-optimal quality, 3-very good quality), 2-3 sufficient for diagnosis. Results The mean time required for careful positioning of the probe and image optimization was 12 ± 3 min and shortened from 13,7 to 11,1 minutes (mean) in first vs second half of the cohort documenting learning curve. At baseline, 9 patients had at least one apical view of quality precluding reliable analysis. Those patients were excluded from further assessment. During stress, 17 patients maintained the optimal or very good quality of all apical views, whereas in 11 patients the quality significantly decreased during the stress test and required probe repositioning. The mean image quality score at baseline was 2,61 ± 0,48 and 2,25 ± 0,6 after exercise. Expectedly, good image quality was easier to obtain and maintain in the supine position (score 2,74 ± 0,44) points as compared with upright position (score 2,25 ± 0,57). Conclusion This preliminary, unique experience with external probe fixation device indicates that continuous acquisition and monitoring of echocardiographic images is feasible during physical exercise, and for the first time ever - also on the treadmill. This feasibility data stem from almost exclusively male patients and the estimated rate of sufficient image quality throughout the entire test is currently around 60%. We are hoping, that gaining more experience with the product could increase the success rate on exercise tests. Abstract P1398 Figure. Treadmill and ergometer stress test

156 Shear wave propagation velocity after aortic valve closure could be a novel parameter for myocardial contractility

Abstract Funding Acknowledgements Research Foundation (FWO) Flanders grant Background Shear wave imaging is a novel ultrasound technique based on the detection of transverse waves travelling through the myocardium by using high frame rate (HFR) echocardiography. These waves can be induced by an external or internal stimulus, such as aortic valve closure (AVC). The propagation velocity of shear waves is directly dependent on myocardial stiffness. It has been previously suggested in animals that the shear wave propagation velocity at AVC might be related to myocardial contractility. Aim The aim of this study was to validate if the shear wave propagation velocity after AVC (end-systole) is related to myocardial contractility. Methods Firstly, 11 healthy volunteers (age: 25 ± 4 years; male: n = 11) performed a supine bicycle exercise test. Images were taken at rest and during 25%, 50% and 66% of maximal workload, as determined by previous upright bicycle exercise testing. Secondly, 9 patients (age: 63 ± 10 years; male: n = 7) underwent a dobutamine stress echocardiography. The stress echo was negative in all patients. Images were taken at rest and after a dobutamine administration of 10µg/kg/min and 40µg/kg/min. Left ventricular (LV) parasternal long axis views were acquired with an experimental HFR ultrasound scanner (HD-PULSE) (average frame rate: 1217 ± 233fps). Apical 4-chamber views were acquired with a conventional ultrasound machine. Non-invasive single beat end-systolic elastance (Ees) was used as a measure of contractility. Acceleration maps were created from HFR-datasets by drawing a M-mode line along the midline of the interventricular septum. Shear wave propagation speed at AVC (end-systole) was calculated by measuring the slope of the wave front on the acceleration maps (Figure A). Results During the bicycle exercise, heart rate (61 ± 11bpm vs. 146 ± 13bpm; p &amp;lt; 0.001), systolic blood pressure (125 ± 12mmHg vs. 173 ± 15mmHg; p &amp;lt; 0.001), LV ejection fraction (55 ± 3% vs. 70 ± 5%; p &amp;lt; 0.001), Ees (1.8 ± 0.3mmHg/ml vs. 3.6 ± 1.0mmHg/ml; p &amp;lt; 0.001) and propagation velocity of the shear waves (3.3 ± 0.5m/s vs. 6.2 ± 1.7m/s; p &amp;lt; 0.01) (Figure B) increased significantly from rest to exercise. Likewise, dobutamine administration significantly increased the heart rate (68 ± 10bpm vs. 131 ± 14bpm; p &amp;lt; 0.001), LV ejection fraction (57 ± 5% vs. 74 ± 7%; p &amp;lt; 0.001), as well as the shear wave velocity after AVC (4.4 ± 0.6m/s vs. 7.2 ± 1.7m/s; p &amp;lt; 0.01) (Figure C) and Ees (2.1 ± 0.4mmHg/ml vs. 3.3 ± 0.8mmHg/ml; p &amp;lt; 0.001). Independent from the stressor, shear wave propagation velocity had a good and significant correlation with Ees (Figure D). Conclusion Shear wave propagation velocity after AVC increases with increasing level of exercise or dobutamine dose. Shear wave velocities at AVC show a good correlation with Ees. Our data indicate that end-systolic shear wave velocity is related to myocardial contractility and might therefore be a potential novel parameter for the non-invasive assessment of myocardial function. Abstract 156 Figure.

Reduced biventricular contractility during exercise in adults with small, unrepaired ventricular septal defects: an echocardiographic study.

Small ventricular septal defects are often considered to be without long-term haemodynamic consequences and so the majority remains unrepaired. However, we recently showed reduced functional capacity and altered right ventricular morphology in adults with small, unrepaired ventricular septal defects. The underlying mechanisms behind these findings remain unclear, and so, biventricular contractility during exercise was evaluated. Adults with small, unrepaired ventricular septal defects and healthy controls were examined with echocardiography during supine bicycle exercise with increasing workload. Tissue velocity Doppler was used for evaluating isovolumetric acceleration and systolic velocities during exercise. In total, 34 patients with ventricular septal defects, a median shunt- ratio of 1.2 (26 ± 6 years), and 28 healthy peers (27 ± 5 years) were included. Right ventricular isovolumetric acceleration was lower in patients as compared with controls at rest (97 ± 40 vs 158 ± 43 cm/s2, P = 0.01) and at peak heart rate (222 ± 115 vs 410 ± 120 cm/s2, P < 0.01). Peak systolic velocities were similar at rest, but differed with exercise (13 ± 3 vs 16 ± 3 cm/s, P = 0.02). Left ventricular isovolumetric acceleration was lower in patients as compared with controls throughout the test (P < 0.01). Septal isovolumetric acceleration was similar at rest, but reduced during increasing exercise as compared with controls (220 ± 108 vs 303 ± 119 cm/s2, P = 0.03). Left ventricular isovolumetric acceleration was negatively correlated with the shunt- ratio, and right ventricular and septal peak systolic velocities were positively correlated with lower functional capacity. Altered biventricular contractility is present during exercise in adults with small, unrepaired ventricular septal defects. These results add to the growing number of studies showing that long-term outcome in unrepaired ventricular septal defects may not be benign.

2380Mechanisms of myocardial ischemia during exercise in microvascular angina

Abstract Background Coronary microvascular dysfunction (MVD) is defined by impaired flow augmentation in response to a vasodilator, the pathophysiological basis of which is unclear. This study sought to address two major gaps in our understanding of MVD: firstly, whether diminished flow reserve is due to structural changes within the microvasculature or potentially reversible dysfunction and secondly to unravel the mechanism of exercise-induced ischemia in the absence of obstructive disease. Methods Simultaneous intracoronary pressure and flow velocity recordings were made in the left anterior descending artery of patients with angina and no obstructive epicardial disease (Fractional Flow Reserve &gt;0.80). Measurements were made at rest, during adenosine-mediated hyperaemia and supine bicycle exercise. Wave intensity analysis was used to quantify waves that accelerate and decelerate coronary blood flow, coronary perfusion efficiency being defined as the proportion of total wave energy that accelerates blood flow. Patients were prospectively classified into MVD (coronary flow reserve &lt;2.5) and controls with researchers blinded to the classification throughout the protocol. Myocardial perfusion and vascular function were assessed by 3T cardiac MRI and venous occlusion plethysmography with forearm blood flow (FBF) assessment during serial infusions of acetylcholine, adenosine and the nitric oxide synthase inhibitor NG-monomethyl-L-arginine (L-NMMA). Results 78 patients were enrolled (42 patients had MVD and 36 were controls), with no differences in cardiovascular risk factors between groups. The MVD group had elevated coronary blood flow (21.3±6.4 vs. 15.1±4.5cm s–1; p&lt;0.001) and global myocardial perfusion (1.36±0.37 vs. 1.13±0.22ml/min/g; p=0.01) at rest. Maximum coronary and myocardial blood flow during hyperaemia was similar in both groups. During exercise, MVD patients achieved similar peak flow (30.5±10.0 vs. 26.3±7.7cm s–1; p=0.07) despite a higher rate-pressure product (20777±5205 vs. 17450±4710bpm.mmHg; p=0.01). Coronary perfusion efficiency, decreased with exercise in the MVD group (61±11% vs. 44±10% p&lt;0.001) but was unchanged in controls. On MRI, MVD had lower hyperaemic endo-epicardial perfusion ratio than controls (0.94±0.08 vs. 1.04±0.13; p=0.001). Augmentation of FBF with acetylcholine was attenuated in MVD patients compared to controls (p=0.02) but the response to adenosine was similar (p=0.13). Infusion of L-NMMA caused a significantly greater reduction in FBF in MVD patients compared to controls (p&lt;0.001). Exercise Physiology in MVD Conclusion Impaired flow reserve in MVD represents a dysfunctional state, characterised by inappropriately elevated resting flow due to increased nitric-oxide synthase mediated vasodilatation. There is abnormal flow distribution in the myocardium predisposing to subendocardial ischaemia, associated with and exacerbated by impaired cardiac-coronary coupling during exercise. These novel findings may represent distinct therapeutic targets. Acknowledgement/Funding British Heart Foundation

P2602Inhaled iloprost improves echocardiographic myocardial performance during exercise in heart failure with preserved ejection fraction

Abstract Introduction The pathophysiology of HFpEF is complicated and treatments that improve outcomes in HFrEF have no substantial benefits in HFpEF. Impairments in LV global longitudinal strain (GLS) and LV diastolic function parameters have been regarded as novel echocardiographic markers to predict cardiovascular events in HFpEF. Preliminary trials indicate that iloprost, an inhaled prostacyclin analougue, improves exercise hemodynamics in both patients with pulmonary artery hypertension and pulmonary hypertension associated with HFpEF. Purpose We aim to investigate the impact of inhaled iloprost on LV global longitudinal strain, LV diastolic function and RV function during exercise in HFpEF population. Methods 34 patients diagnosed with HFpEF were included with exclusion of severe pulmonary, coronary artery, valvular heart and pericardial diseases. Subjects were randomized 1:1 to inhalation of iloprost or placebo. Transthoracic echocardiography was performed at rest and after 6-minute supine bicycle exercise at 20-Watt workload. We utilized tissue speckle tracking by QLAB software to derive LV GLS and global strain rate during LV isovolumetric relaxation period (SRIVR). E/e', E/SRIVR, tricuspid regurgitation pressure gradient (TRPG), tissue Doppler imaging of RV lateral tricuspid annulus and tricuspid annular plane systolic excursion (TAPSE) were measured to evaluate changes of myocardial performance. Results LV GLS during exercise significantly enhanced after iloprost use. E/SRIVR, a novel predictor of LV filling pressure, was significantly decreased. E/e' was also lower in iloprost group by trend. Improvements in RV function and degree of pulmonary hypertension during exercise with iloprost were observed in this study. Echocardiographic myocardial function endpoints during 20-Watt excercise between iloprost and placebo groups Iloprost (N=17) Placebo (N=17) P value LV global longitudinal strain, % −4.96±1.20 −0.75±3.00 &lt;0.001 E/SRIVR, cm 206.41±113.55 454.13±262.98 0.005 E/e' mean 10.77±2.39 14.41±12.14 0.235 TAPSE, cm 2.62±0.62 2.37±0.56 0.221 TRPG, mmHg 28.37±12.47 44.25±9.29 &lt;0.001 TDI lateral tricuspid annulus, cm/s 16.41±4.61 14.77±2.92 0.222 Effects of iloprost at rest and exercise Conclusions Our study is the first to demonstrate that, in patients with HFpEF, inhaled iloprost favorably enhances LV GLS reserves, decreases LV diastolic filling load, reduces pulmonary hypertension and thereby improves RV function during exercise. Acknowledgement/Funding This work was supported in part by the National Science Council of the Republic of China, Taiwan (NSC107-2314-B-002-265-MY3)