TY - JOUR
AU1 - Reant, Patricia
AU2 - Dufour, Maxence
AU3 - Peyrou, Jerome
AU4 - Reynaud, Amelie
AU5 - Rooryck, Caroline
AU6 - Dijos, Marina
AU7 - Vincent, Cecile
AU8 - Cornolle, Claire
AU9 - Roudaut, Raymond
AU1 - Lafitte, Stephane
AB - Abstract Aims Recent findings regarding hypertrophic cardiomyopathy (HCM) haemodynamics emphasized the relationship between symptoms, left ventricular outflow tract obstruction (LVOTO), and the preload condition as the venous return level. As various types of exercises have different effects on peripheral vascular beds, this study sought to compare upright treadmill exercise echocardiography (EE) to semi-supine bicycle EE in maximum provoked LVOTO in HCM patients. Methods and results Semi-supine bicycle and upright treadmill EE were prospectively performed in HCM patients with New York Heart Association functional Class II. Maximal LVOT gradient at rest in the supine and standing position, and during Valsalva manoeuvre, LVOT gradients of both semi-supine bicycle and treadmill exercise at peak and post-exercise, maximal exercise levels, and blood pressure adaptation were recorded. One patient was excluded for not sufficient image quality during treadmill. We studied 22/23 patients (mean age: 54.9 ± 12.3 yrs; 55% male). The supine position at rest displayed a mean maximal LVOT gradient of 46.1 ± 44.8 mmHg, which increased to 51.6 ± 41.2 mmHg during Valsalva (P = 0.066), and to 55.1 ± 37.8 mmHg in the standing position (P = 0.053). Mean maximal peak exercise LVOT gradient with semi-supine bicycle was significantly lower than in treadmill EE (54.6 ± 38.2 mmHg vs. 87.5 ± 42.1 mmHg, respectively, P < 0.01). Among these patients, 41% exhibited LVOT gradient ≥ 30 mmHg at rest. Moreover, 41% exhibited LVOT gradient ≥ 50 mmHg during Valsalva, 55% in resting standing position, 41% at peak semi-supine bicycle exercise, 91% at peak treadmill exercise, and 95% in standing position during treadmill recovery period. Conclusion This pilot study may suggest treadmill’s greater value compared to semi-supine bicycle EE for determining maximum LVOT gradient in HCM. echocardiography, exercise echocardiography, hypertrophic cardiomyopathy, Treadmill exercise Introduction About 50–60% of patients with hypertrophic cardiomyopathy (HCM) suffer from dyspnoea on exertion, which can be the result of dynamic left ventricular (LV) outflow tract obstruction (LVOTO).1,2 LVOTO is a complex mechanism depending on LV morphology, loading conditions, contractility or mitral apparatus, and valve length.3–6 While pharmacological stress echocardiography (e.g. isoprenaline, amyle nitrite) or Valsalva manoeuvre were initially used and are recommended by current guidelines to unmask LVOTO,1,7,–9 exercise echocardiography (EE) can also be performed as a more physiological approach directly linked to day-to-day symptoms.9 Post-exercise evaluation, after supine repositioning, does not enable evaluation of cardiac mechanisms and haemodynamics during exercise.1,5,10 Although per-exercise methods have been considered to closely mimic physiology and daily-life activity, several techniques have been considered and are used, which may differ among centres, such as semi-supine bicycle, upright bicycle,2,6,11,12 or upright treadmill EE.3,5 Recent haemodynamic studies in HCM tend to link symptoms, LVOTO, and preload conditions to the venous return level.5,11 As various types of exercises have different effects on peripheral vascular beds, and thereby on preload conditions, we subsequently hypothesized that distinctive types of exercises could have varying effects on LVOTO. This study sought to compare semi-supine bicycle to upright treadmill EE. The former is validated for exploring cardiac function during echocardiography, being physiologically associated with a considerably increased venous return, while treadmill exercise is closer related to life activities and associated with less increased venous return due to gravity. A second study objective was to assess treadmill EE feasibility compared to semi-supine bicycle EE. Methods Study protocol From October to November 2015, all HCM patients referred to our Competence Center in Cardiomyopathies were prospectively evaluated using clinical parameters and 2D echocardiography at rest, then trying to provoke maximal LVOT gradient during cycling exercise, and, following a recovery period of at least 30 min, the test was repeated during treadmill exercise to compare the two tests’ capacity to provoke maximum peak exercise gradient. The inclusion criteria were: (i) patients with echocardiographic documentation of LV hypertrophy (wall thickness ≥15 mm, in the absence of other diseases that may cause a similar degree of hypertrophy13) and, in addition, either positive genetic tests or familial HCM history; (ii) New York Heart Association (NYHA) functional Class II; (iii) sinus rhythm; and (iv) ability to perform exercise testing. The exclusion criteria for the patients were: (i) inability to perform exercise, (ii) poor quality window on supine evaluation, (iii) recent history of syncope or severe arrhythmia, (iv) persistent atrial fibrillation, (v) apical LV hypertrophy, (vi) contraindication to EE, and (vii) longstanding or severe uncontrolled hypertension. Detailed information regarding the study and data collection was provided to all patients, and the ethics committee approved the study protocol. Echocardiography at rest Echocardiography was performed according to current guidelines,14,15 by an experienced operator16 using a Vivid E9 Ultrasound System (General Electric Medical System, Horten, Norway). Recordings in standardized views were acquired in 2D (50–75 ips), pulsed, continuous, colour, and pulsed tissue Doppler modalities, then stored for subsequent analysis. Particular attention was paid to the LVOT area to identify and analyse the mitral valve systolic anterior motion. The LVOT was scanned employing continuous Doppler to measure maximal outflow gradient. Exercise test EEs were conducted in accordance with European Association of Echocardiography (EAE) guidelines.17 Evaluations were performed in the morning, first, during bicycle exercise in a semi-supine position and, then, following a period of at least 30 min [allowing heart rate, blood pressure (BP), LVOT gradient, LV ejection fraction (LVEF), and pulmonary artery systolic pressure to return to baseline values], during treadmill exercise. Both examinations were carried out in the same room. Bicycle exertion in semi-supine position (50°) was performed with a slight left lateral tilt. The experienced operator used the same Vivid E9 machine. Starting at 25 watts, the workload was increased by 25 watts every 2 min up to the maximum tolerated effort. Maximal load in Watts was converted to METS according to the formula: level in METS (ml/min/kg) = {(12.3 × load in watts) + (3.5 × weight)}/(3.5 × weight). Treadmill exertion was performed using the T2100 machine by a second experienced operator blinded from bicycle exercise, also using the same echocardiographic machine. The modified Bruce protocol was applied.10 Starting at 2.2 METS, the workload was increased every 3 min. up to the maximum tolerated effort. To avoid the risk of comparing the two experienced operators' ability to detect LVOT gradient, the first and second observers alternated for evaluating bicycle exercise or treadmill exercise for each patient. For each exercise, at each stage from rest to the 6-min recovery period, conventional recordings were acquired in 2D views and continuous and colour Doppler modalities, and stored for offline analysis. In addition to ECG, systolic and diastolic BPs were recorded at each stage. Inadequate BP response to exercise was defined by an increase in systolic BP < 25 mmHg or a drop in systolic BP at peak ≥ 15 mmHg. Echocardiographic measurements at rest An independent observer, blinded to patients' history, performed a retrospective analysis on all cases, applying standard measurements according to EAE/ASE guidelines and using the echography’s internal quantitation package. Maximal end-diastolic wall thickness was measured on 2D. LV diameters, LV volumes, and LVEF were calculated from apical views using Simpson’s rule.14 Biplane maximal left atrial volume (area-length method) was indexed to body surface area. The mean E/e’ ratio was calculated. Systolic pulmonary artery pressure was calculated based on the measured tricuspid gradient and estimated right atrial pressure from inferior vena cava size and degree of collapse.18 Mitral regurgitation (MR) was graded (0–4) using the Proximal Isovelocity Surface Area (PISA) method. In the event of non-central jets, colour jet extension in the three main apical views and the peak mitral E-wave velocity were also considered. Longitudinal LV deformation was measured using the 2D speckle-tracking method.12 Global longitudinal strain was obtained for apical views. Systolic anterior motion was considered present only in the event of complete systolic apposition of the mitral valve on the septum. Outflow velocities were measured using continuous-wave Doppler (in the supine position, during Valsalva manoeuvre, and in standing position). Outflow gradients were measured and automatically calculated.19 Specific attention was paid not to confuse MR flow when present. EE parameters During exercise, MR, if present, was graded (0–4) following the same method than at rest. During both exercise and post-exercise evaluation, outflow velocities were measured using continuous-wave Doppler, with the same direction and angle as recorded at rest. Specific attention was paid not to confuse MR flow when present. Definitions According to current guidelines,9,20 significant obstruction at rest in the supine position was defined for LVOT gradient ≥ 30 mmHg, and during provocation manoeuvres for LVOT gradient ≥ 50 mmHg, as this is the cut-off threshold considered clinically relevant in the decision-making process regarding the need for invasive septal reduction therapy.1,11,12 We have defined the ‘increase’ in LVOT gradient, meaning an increase of at least 30 mmHg, during each provocative condition, compared to the evaluation at rest in the supine position. According to our recent publication,11 we have defined significant ‘decrease’ in LVOT gradient during each provocative condition by a decrease of at least 30 mmHg compared to the evaluation at rest in the supine position. Statistical analysis Continuous and qualitative variables were expressed as mean, standard deviation (SD), and discrete variables as absolute numbers and percentages. Descriptive data were analysed for normality using visual histograms and the Shapiro–Wilks test. The groups were first tested using a Chi-squared and Fischer’s exact test to compare categorical variables. Then, continuous data were compared using 2-sample Student’s t-test (with Welch’s approximation if unequal variance was found) or Wilcoxon’s rank-sum (Mann–Whitney) non-parametric tests as appropriate according to the variance R-test. Inter-observer reproducibility of peak treadmill EE maximum LVOTO gradient was performed by offline quantitation by two independent operators in all patients (n = 22). Mean ± SD of the absolute difference between the two measurements was calculated and a Bland–Altman difference plot analysis was also performed to measure the agreement between the two operators. The slope of regression line has been drawn and the coefficient of determination R2 was calculated. The intraclass correlation coefficient was calculated using a one-way random-effects model to estimate the correlation between individual measurements. All P-values were two-sided, and values < 0.05 were considered statistically significant. All statistical analyses were performed using Stata software version 11.0 (StataCorp LP, College Station, TX). Results Study population Over 61 consecutive patients, this prospective study enrolled and included 23 HCM patients. Figure 1 displays the flow chart. One patient was excluded due to a poor acoustic window during treadmill exercise. We thus studied 22/23 patients. Figure 1 View largeDownload slide Flow chart. Figure 1 View largeDownload slide Flow chart. The population’s baseline clinical and demographical characteristics are presented in Table 1. Mean age was 54.9 ± 12.3years, of which 55% were male. Table 1 Clinical and demographic characteristics   Value(n=22)  Demographical variables    Male gender, n (%)  12 (55)  Age (years)  54.9 ± 12.3  Clinical variables    Body mass index (kg/m2)  26.6 ± 4.3  Systolic blood pressure (mmHg)  127 ± 20  Diastolic blood pressure (mmHg)  75 ± 14  Heart rate (beats/min)  60.8 ± 8.4  NYHA Class II, n (%)  22 (100)  Familial history of HCM, n (%)  7 (32)  Hypertension, n (%)  8 (36)  Chest pain, n (%)  5 (23)  Syncope, n (%)  3 (14)  Therapies    Implantable cardioverter defibrillator, n (%)  5 (23)  Pacemaker, n (%)  3 (14)  Myectomy, n (%)  1 (5)  Septal alcohol ablation, n (%)  2 (9)  Beta-blockers, n (%)  20 (91)  Calcium antagonists, n (%)  3 (14)    Value(n=22)  Demographical variables    Male gender, n (%)  12 (55)  Age (years)  54.9 ± 12.3  Clinical variables    Body mass index (kg/m2)  26.6 ± 4.3  Systolic blood pressure (mmHg)  127 ± 20  Diastolic blood pressure (mmHg)  75 ± 14  Heart rate (beats/min)  60.8 ± 8.4  NYHA Class II, n (%)  22 (100)  Familial history of HCM, n (%)  7 (32)  Hypertension, n (%)  8 (36)  Chest pain, n (%)  5 (23)  Syncope, n (%)  3 (14)  Therapies    Implantable cardioverter defibrillator, n (%)  5 (23)  Pacemaker, n (%)  3 (14)  Myectomy, n (%)  1 (5)  Septal alcohol ablation, n (%)  2 (9)  Beta-blockers, n (%)  20 (91)  Calcium antagonists, n (%)  3 (14)  Values are expressed as mean ± SD or n (%). Echocardiography at rest Echocardiography at rest characteristics are presented in Table 2. Mean LV maximal wall thickness was 19.1 ± 3.8mm. Five (23%) patients exhibited moderate MR, while none had severe MR. Table 2 Resting echocardiographic characteristics Echocardiographic parameter  Value(n=22)  LV maximal wall thickness (mm)  19.1 ± 3.8  LV end-diastolic volume (mL/m2)  41.6 ± 8.2  LV end-systolic volume (mL/m2)  13.5 ± 5.9  LV ejection fraction (%)  71.5 ± 5.4  Global longitudinal strain (%)  −15.9 ± 3.9  Mean E/e’  11.6 ± 3.8  Left atrial diameter (mm)  45.3 ± 7.7  Left atrial volume index (mL/m2)  44.9 ± 16.0  Pulmonary systolic artery pressure (mmHg)  30.1 ± 8.6  Vena cava diameter (mm)  15.9 ± 3.8  MR grade    None or trivial, n (%)  3 (14)  Mild, n (%)  14 (64)  Moderate, n (%)  5 (23)  Systolic anterior motion, n (%)  15 (68)  LVOT gradient at rest (mmHg)  46.1 ± 44.8  LVOT gradient/Valsalva (mmHg)  51.6 ± 41.2  LVOT gradient in standing position (mmHg)  55.1 ± 37.8  Echocardiographic parameter  Value(n=22)  LV maximal wall thickness (mm)  19.1 ± 3.8  LV end-diastolic volume (mL/m2)  41.6 ± 8.2  LV end-systolic volume (mL/m2)  13.5 ± 5.9  LV ejection fraction (%)  71.5 ± 5.4  Global longitudinal strain (%)  −15.9 ± 3.9  Mean E/e’  11.6 ± 3.8  Left atrial diameter (mm)  45.3 ± 7.7  Left atrial volume index (mL/m2)  44.9 ± 16.0  Pulmonary systolic artery pressure (mmHg)  30.1 ± 8.6  Vena cava diameter (mm)  15.9 ± 3.8  MR grade    None or trivial, n (%)  3 (14)  Mild, n (%)  14 (64)  Moderate, n (%)  5 (23)  Systolic anterior motion, n (%)  15 (68)  LVOT gradient at rest (mmHg)  46.1 ± 44.8  LVOT gradient/Valsalva (mmHg)  51.6 ± 41.2  LVOT gradient in standing position (mmHg)  55.1 ± 37.8  Values are expressed as mean ± SD or n (%). LV,  left ventricular; LVOT,  left ventricular outflow-tract; MR, mitral regurgitation. At rest, in the supine position, mean maximal LVOT gradient was 46.1 ± 44.8 mmHg, and 9 (41%) patients had LVOT gradient ≥30 mmHg. Table 3 displays increase (or decrease) of the LVOT gradient of at least 30 mmHg during each provocative condition compared to evaluation at rest in the supine position, as well as percentage of patients with provoked LVOT gradient ≥ 50 mmHg. Table 3 Evolution of LVOT gradient during provocative conditions compared to rest supine Conditions  Increase ≥30mmHg  Decrease ≥30mmHg  LVOT gradient ≥50mmHg  Valsalva, n (%)  2 (9)  0 (0)  9 (41)  Standing position, n (%)  4 (18)  2 (9)  12 (55)  Bicycle exercise, n (%)  5 (23)  2 (9)  9 (41)  Treadmill exercise, n (%)  14 (64)  1 (4)  20 (91)  Post-bicycle exercise, n (%)  11 (50)  1 (4)  14 (64)  Post-treadmill exercise, n (%)  15 (68)  0 (0)  21 (95)  Conditions  Increase ≥30mmHg  Decrease ≥30mmHg  LVOT gradient ≥50mmHg  Valsalva, n (%)  2 (9)  0 (0)  9 (41)  Standing position, n (%)  4 (18)  2 (9)  12 (55)  Bicycle exercise, n (%)  5 (23)  2 (9)  9 (41)  Treadmill exercise, n (%)  14 (64)  1 (4)  20 (91)  Post-bicycle exercise, n (%)  11 (50)  1 (4)  14 (64)  Post-treadmill exercise, n (%)  15 (68)  0 (0)  21 (95)  LVOT,  left ventricular outflow-tract. During Valsalva manoeuvre, LVOT gradient increased up to 51.6 ± 41.2 mmHg (P = 0.067 vs. rest supine). In the standing position, mean maximal LVOT gradient increased to 55.1 ± 37.8 mmHg (P = 0.14 vs. supine position). Twelve (55%) patients had LVOT gradient ≥ 50 mmHg while only 9 (41%) with Valsalva (Table 3). Exercise echocardiographies Feasibility of LVOT gradient evaluation during bicycle and treadmill exercises was 100% and 96%, respectively. The maximal workload reached was similar (P = 0.26) (Table 4). The maximal peak exercise provoked LVOT gradient was 54.6 ± 38.2 mmHg in bicycle EE vs. 87.5 ± 42.1 mmHg in treadmill EE (P < 0.01). Table 4 Exercise characteristics   Semi-supine bicycle (n=22)  Upright treadmill (n=22)  P-value  Clinical variables        Max level (METS)  5.5 ± 1.2  6.3 ± 3.2  0.26  Peak systolic BP (mmHg)  152 ± 20  159 ± 28  0.36  Peak diastolic BP (mmHg)  85 ± 12  88 ± 23  0.54  Peak heart rate (bpm)  115 ± 17  114 ± 22  0.58  NSVT during exercise, n (%)  0 (0)  0 (0)  NA  Inadequate BP response, n (%)  11 (50)  9 (41)  0.19  Echocardiographic variables        MR grade        None or trivial  3 (14)  2 (9)  0.001  Mild  13 (59)  14 (64)  Moderate  5 (23)  4 (18)  Severe  1 (4)  2 (9)  Peak exercise LVOT gradient (mmHg)  54.6 ± 38.2  87.5 ± 42.1  <0.01  Peak LVOT gradient≥50mmHg, n (%)  9 (41)  20 (91)  0.22  Post-exercise LVOT gradient (mmHg)  75.6 ± 45.0  91.5 ± 40.8  0.23  Post-exercise LVOT gradient≥50mmHg, n (%)  17 (77)  21 (95)  0.18  Difference peak EE-rest LVOT gradient (mmHg)  8.4 ± 31.9  41.3 ± 34.7  0.002  Difference peak EE-Valsalva LVOT gradient (mmHg)  3.0 ± 26.8  35.9 ± 32.8  0.0004  Difference peak EE-standing LVOT gradient (mmHg)  −0.5 ± 27.2  32.4 ± 28.8  0.0003    Semi-supine bicycle (n=22)  Upright treadmill (n=22)  P-value  Clinical variables        Max level (METS)  5.5 ± 1.2  6.3 ± 3.2  0.26  Peak systolic BP (mmHg)  152 ± 20  159 ± 28  0.36  Peak diastolic BP (mmHg)  85 ± 12  88 ± 23  0.54  Peak heart rate (bpm)  115 ± 17  114 ± 22  0.58  NSVT during exercise, n (%)  0 (0)  0 (0)  NA  Inadequate BP response, n (%)  11 (50)  9 (41)  0.19  Echocardiographic variables        MR grade        None or trivial  3 (14)  2 (9)  0.001  Mild  13 (59)  14 (64)  Moderate  5 (23)  4 (18)  Severe  1 (4)  2 (9)  Peak exercise LVOT gradient (mmHg)  54.6 ± 38.2  87.5 ± 42.1  <0.01  Peak LVOT gradient≥50mmHg, n (%)  9 (41)  20 (91)  0.22  Post-exercise LVOT gradient (mmHg)  75.6 ± 45.0  91.5 ± 40.8  0.23  Post-exercise LVOT gradient≥50mmHg, n (%)  17 (77)  21 (95)  0.18  Difference peak EE-rest LVOT gradient (mmHg)  8.4 ± 31.9  41.3 ± 34.7  0.002  Difference peak EE-Valsalva LVOT gradient (mmHg)  3.0 ± 26.8  35.9 ± 32.8  0.0004  Difference peak EE-standing LVOT gradient (mmHg)  −0.5 ± 27.2  32.4 ± 28.8  0.0003  Values are expressed as mean ± SD or n (%). BP, blood pressure; EE, exercise echocardiography; LVOT,  left ventricular outflow-tract. The maximal LVOT gradient during exercise was significantly increased compared to resting conditions in the supine position with P-values of <0.039 during bicycle exercise, and P < 0.001 for treadmill exercise. Compared to rest in the supine position, LVOT gradient increased of at least 30 mmHg in 23% patients during bicycle exercise, and in 64% during treadmill (Table 3). At peak bicycle exercise, 9 (41%) of the patients had LVOT gradient ≥ 50 mmHg, while there were 20 (91%) at peak treadmill. In the recovery period, again, on bicycle, 64% of the patients had LVOT gradient ≥ 50 mmHg while there were 21 (95%) after treadmill, staying in standing position (Table 3). Inter-observer reproducibility of peak maximal LVOT gradient during treadmill was good; mean ± SD of the absolute difference between the two measurements was 4.6 ± 3.5 mmHg. Figure 2 displays the results of Bland-Altman analysis. The intraclass correlation coefficient was 0.97 (CI95%: 0.74–0.99) showing a very good correlation between measurements. Figure 2 View largeDownload slide Bland–Altman analysis for LVOT gradient during treadmill exercise inter-observer measurement reproducibility. Figure 2 View largeDownload slide Bland–Altman analysis for LVOT gradient during treadmill exercise inter-observer measurement reproducibility. Comparison of provoked LVOTO using different modalities Figure 3 displays the mean of maximal LVOT gradient in each condition, and the comparison of the different modalities. Treadmill exercise and post-exercise evaluation of LVOT gradient in the standing position allows obtaining the highest LVOT gradient values responsible of daily-life activities patient’s dyspnoea. Figure 4 displays the percentage of patients with LVOT gradient ≥ 30 mmHg at rest, and LVOT gradient ≥ 50 mmHg in each provocative condition. Figure 5 shows individual data. One patient did not develop any obstruction, and only one developed greater obstruction during bicycle than with treadmill EE. Two patients (9%) decreased their LVOT gradient of at least 30 mmHg during standing position and during bicycle exercise (paradoxical response to exercise) (Table3). Figure 3 View largeDownload slide Box-plot of maximal LVOT gradient in each condition: at rest, Valsalva, standing position, peak bicycle exercise, recovery after bicycle exercise, peak treadmill exercise, and recovery after treadmill (upright). Figure 3 View largeDownload slide Box-plot of maximal LVOT gradient in each condition: at rest, Valsalva, standing position, peak bicycle exercise, recovery after bicycle exercise, peak treadmill exercise, and recovery after treadmill (upright). Figure 4 View largeDownload slide Percentage of HCM patients with maximal LVOT gradient ≥30mmHg at rest or ≥50 mmHg in other conditions. Figure 4 View largeDownload slide Percentage of HCM patients with maximal LVOT gradient ≥30mmHg at rest or ≥50 mmHg in other conditions. Figure 5 View largeDownload slide Individual data of maximal LVOT gradient in each condition. Figure 5 View largeDownload slide Individual data of maximal LVOT gradient in each condition. Over the 20 patients who developed LVOT gradient ≥ 50 mmHg during treadmill exercise, only 9 (45%) presented LVOT gradient ≥ 50 mmHg during bicycle exercise. Discussion From our knowledge, this is the first study really comparing two (per-)exercise modalities of LVOTO evaluation in HCM, and confirming the value of echocardiography in the standing position (at rest, and after treadmill exercise) and during treadmill exercise for LVOTO provocation in symptomatic HCM patients. Our study strengthens the relevance of the treadmill exercise value that allows a more advanced physiological LVOTO gradient provocation during exercise, previously shown to correlate with symptoms developed by HCM patients in their everyday life activities. It also emphasizes its ability to provoke higher LVOT gradient, as compared to Valsalva manoeuvre or semi-supine bicycle exercise. Moreover, it supports the safety, good reproducibility, and good feasibility (96%) of this evaluation for operators experienced in EE. Post-exercise echocardiographic evaluation after supine repositioning in HCM Maron et al.1 were the first to demonstrate the value of studying LVOTO as a dynamic phenomenon after exercise. Vaglio et al.2 investigated clinical characteristics and outcomes of HCM patients with latent obstruction in post-exercise after supine repositioning. After exercise, the sudden LV preload reduction plus adrenergic response during this phase accounts for the LVOT gradient increase. However, the obstruction during the recovery period is not fully representative of that occurs when the patients is really developing symptoms. In addition, in daily life, most patients walking or running, remain in the standing position after exercise and do not lie down. For this reason, post-exercise echocardiography after supine repositioning does not appear fully satisfactory. Moreover, Cotrim et al.10 have elegantly highlighted that post-exercise (treadmill) evaluation of the LVOT gradient is more relevant with the patient in the standing position compared to the supine position. In all patients with obstructive HCM, the intra-ventricular gradient increased during orthostatic recovery, in their study. In our study, only one patient did not exhibit a LVOT gradient ≥50 mmHg in the recovery period while in the standing position. Per-exercise echocardiography on a bicycle ergometer Exercise echocardiography and evaluation of LVOTO during exercise, particularly at peak exercise, have recently been recommended. It closely resembles daily-life activities and circumstances of symptom occurrence. The most-used method is the semi-supine bicycle exercise. It offers benefits in echo recording, as it is relatively comfortable for the operator and requires less physical effort than treadmill exercise. Recently, we have observed that LVOT gradient may ‘paradoxically’ decrease during semi-supine bicycle exercise in NYHA functional class I or II HCM patients.11 At rest, 69/120 patients showed no LVOTO, while 38 exhibited LVOTO ≥ 50 mmHg. Among these 69, 9 (24%) exhibited a gradient decrease ≥30 mmHg during exercise. Cycling induces more venous friction and venous return due to the predominant activity of the thigh muscles, which might mask maximal LVOT gradient. This phenomenon was also observed in the present investigation. The resting LVOT gradient decreased of at least ≥30 mmHg during bicycle exercise in 2 of our 22 study patients. Moreover, the LVOT gradient did not increase to ≥50 mmHg in 11 (55%) of our study patients during bicycle exercise, while it increased to ≥50 mmHg in each of these 11 patients and in 20 of our 21 study patients during treadmill exercise. Mechanisms of abnormal vascular response in HCM patients Pre-load conditions are directly linked to venous vascular return. In HCM patients, abnormal vascular responses and instability have previously been reported, such as inappropriate vasodilator response in non-exercising venous capacitance beds, excess stimulation of LV mechanoreceptors by abnormal wall strains, and exaggerated sensitivity of baroreceptors.21 In a recent study, autonomic response to passive orthostatism in HCM patients was evaluated, likely correlating to specific functional features of the hypertrophic heart.22 HCM patients with parasympathetic response to passive orthostatism, and consequently vein dilatation accentuated by the orthostatic position, were more likely to have a higher NYHA functional class, more frequent history of atrial fibrillation or syncope, and increased isovolumic relaxation time.22 Consequently, in some HCM patients, transitioning from the supine to the standing position may lead to a drop in venous peripheral resistance due to inadaptation, thereby generating a decrease in LV preload, later responsible for an increased LVOT gradient. In HCM patients with peripheral vascular abnormalities and a deficient venous return at rest, cycling by tonic muscular venous friction, which restores the venous return to some extent, the maximal LVOT gradient provoked by exercise may not be achieved. Similarly, provocative manoeuvres performed in the supine do not fully reflect the symptoms and maximal obstruction occurring in HCM patients during their daily-life activities, as venous return is partially restored on account of the patient's positioning. In addition, contrary to cycling, treadmill exercises tend to enhance the lack of venous tonus that pre-exists at rest, in at least a part of the HCM patients. This further illustrates the crucial role of vascular resistances in LVOTO. Treadmill vs. semi-supine bicycle exercise echocardiography LVOTO evaluation during treadmill was previously suggested.3,5,23 To date, from our knowledge, a direct comparison between bicycle and treadmill exercises was, however, not performed. Our study clearly points out that, in comparison with treadmill, the semi-supine bicycle exercise is less reflective of both provocable symptoms and maximal LVOT gradient, which may occur in HCM patients. Performing an LVOT gradient evaluation at rest in the standing position and perhaps also, after treadmill exercise for each HCM patient appears crucial, and treadmill exercise should thus be recommended as often as possible on condition that it is performed by a trained EE operator. Limitations The main limitation of our study is the relatively small sample size. Larger, multicentre studies are needed to strengthen our results. We also acknowledge that treadmill exercise was performed after bicycle exercise, and not a different day, which could be considered a limitation to our study. However, we took great care to ensure that each patient had returned to its baseline parameters and that workload was similar between the two exercises. Wall motion analysis during treadmill exercise was not performed, as decision was taken to focus on LVOT gradient evaluation. In line with a recent publication,23 it would be interesting to analyse the prognostic value of wall motion during treadmill exercise. Clinical implications Supine evaluation of LVOT gradient at rest and during Valsalva, are not sufficient, and semi-supine bicycle exercise can miss LVOTO provocation. These results are crucial as we need to standardize EE between centers.24 Moreover, evaluation in the standing position at rest, during and after treadmill exercise (in standing position) is safe, feasible, and should be considered in HCM patient’s routine evaluation, particularly those with NYHA functional class II or III. In line with the seminal work of authors like Dimitrow and Cotrim, we would recommend conducting treadmill exercise, instead of Valsalva or semi-supine bicycle exercise, in order to provoke maximal LVOT gradient (responsible of cardiac symptom occurrence) during effort, each time it is possible, for every HCM patient who is able to perform exercise, while respecting actual international guidelines on contra-indications to exercise.20 It appears crucial, indeed, to reproduce real-life exercise activities allowing us to assess the link between symptoms and obstruction level. Moreover, post-exercise LVOTO in the standing position as promoted by Cotrim et al.10 also appears to be an attractive alternative. Future studies will need to assess the prognostic values of such per- and post-exercise evaluations, in particular as regards patient stratification based on the sudden cardiac death risk score. On note is that the evaluation methods employed may likely impact the sudden cardiac death risk stratification, as maximal LVOT gradient provocation is part of the new calculator risk score based on the 2014 ESC recommendations.20 Conclusion This study has confirmed the good feasibility of treadmill EE for an experimented EE operator and may suggest the greater value of this method to obtain maximal exercise provocable LVOT gradient compared to semi-supine bicycle EE. Larger, multicentre studies are, however, needed to further strengthen these results. Conflicts of interest: None declared. References 1 Maron MS, Olivotto I, Zenovich AG, Link MS, Pandian NG, Kuvin JT et al.   Hypertrophic cardiomyopathy is predominantly a disease of left ventricular outflow tract obstruction. Circulation  2006; 114: 2232- 9. Google Scholar CrossRef Search ADS PubMed  2 Vaglio JC, Ommen SR, Nishimura RA, Tajik AJ, Gersh BJ. 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TI - Upright treadmill vs. semi-supine bicycle exercise echocardiography to provoke obstruction in symptomatic hypertrophic cardiomyopathy: a pilot study
JF - European Heart Journal – Cardiovascular Imaging
DO - 10.1093/ehjci/jew313
DA - 2018-01-01
UR - https://www.deepdyve.com/lp/oxford-university-press/upright-treadmill-vs-semi-supine-bicycle-exercise-echocardiography-to-6ALVcKfsg7
SP - 31
EP - 38
VL - 19
IS - 1
DP - DeepDyve
ER -