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Exercise Testing in Patients with Asymptomatic Moderate Or Severe Aortic Stenosis

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Exercise Testing in Patients with Asymptomatic Moderate Or Severe Aortic Stenosis Heart Online First, published on April 13, 2018 as 10.1136/heartjnl-2018-312939 Valvular heart disease ORIGINAL RESEARCH ARTICLE Heart: first published as 10.1136/heartjnl-2018-312939 on 13 April 2018. Downloaded from Exercise testing in patients with asymptomatic moderate or severe aortic stenosis Sahrai Saeed,1,2 Ronak Rajani,1 Reinhard Seifert,2 Denise Parkin,1 John Boyd Chambers1 1Cardiothoracic Centre, Guy’s & ABSTRact there have been some residual concerns about St Thomas’ Hospital, London, UK 2 Objective To assess the safety and tolerability of safety and tolerability. This may partly explain why Department of Heart Disease, ETT was performed in only 5.7% of patients in Haukeland University Hospital, treadmill exercise testing and the association of revealed Bergen, Norway symptoms with outcome in apparently asymptomatic the EuroHeart survey with severe AS in whom it patients with moderate to severe aortic stenosis (AS). was indicated.6 In fact, little data on the safety and Correspondence to Methods A retrospective cohort study of 316 patients tolerability of exercise testing in large populations Dr Sahrai Saeed, Department (age 65±12 years, 67% men) with moderate and severe of moderate to severe asymptomatic AS exist. Thus, of Heart Disease, Haukeland AS who underwent echocardiography and modified our aim was to assess: (1) the safety and tolerability University Hospital, Bergen of ETT; (2) the association of revealed symptoms 5021, Norway; sahrai. saeed@ Bruce exercise treadmill tests (ETTs) at a specialist helse- bergen. no valve clinic. The outcome measures were aortic valve with outcome; and (3) the prognostic significance replacement (AVR), all-cause mortality or a composite of of serial ETT in apparently asymptomatic moderate Received 2 January 2018 AVR and all-cause mortality. or severe AS patients. Revised 22 March 2018 Results At baseline, there were 210 (66%) patients Accepted 23 March 2018 with moderate and 106 (34%) with severe AS. There were 264 (83%) events. 234 (74%) patients reached an METHODS indication for AVR, 145 (69%) with moderate and 88 Patient population (83%) with severe AS (p<0.05). Of the 30 (9%) deaths Between January 2000 and May 2017, a total of recoded during follow-up, 20 (67%) were cardiovascular 651 patients aged >18 years with moderate (effec- 2 related. In total, 797 exercise tests (mean 2.5±2.1 per tive orifice area (EOA) 1.0–1.5 cm ) or severe 2 3 4 patient) were performed. No serious adverse events (EOA <1.0 cm ) AS were assessed in dedicated were observed. The prevalence of revealed symptoms heart valve clinic at Guy’s and St Thomas’ Hospital. at baseline ETT was 29% (n=91) and was significantly During a median follow-up of 25 months (mean higher in severe AS compared with moderate AS 34.9±35.1 months), only seven patients were lost http://heart.bmj.com/ (38%vs23%, p=0.008). Symptoms were revealed in to follow-up. Patients were excluded from the 18%–59% of patients during serial ETT conducted study if they declared spontaneous symptoms justi- over a follow-up period of 34.9 (SD 35.1) months. The fying surgery on the history (n=283), had more event-free survival at 24 months with revealed symptoms than moderate coexistent additional valve disease was 46%±4% and without revealed symptoms was (12 patients with severe mitral regurgitation, 4 70%±4%. with severe mitral stenosis and 5 with severe aortic Conclusions ETT in patients with moderate or severe regurgitation) or had an inability to exercise owing AS is safe and tolerable. Serial exercise testing is useful to concomitant comorbidities such as peripheral on September 27, 2021 by guest. Protected copyright. to reveal symptoms not volunteered on the history and vascular disease (n=2), chronic obstructive pulmo- adds incremental prognostic information to baseline nary disease (n=24), anaemia (n=2) immobility or testing. severe arthritis (n=3). The remaining 316 patients (49%) were apparently asymptomatic by history and eligible for inclusion in the present EXercise Testing in AS (EXTAS) study, a retrospective anal- INTRODUCTION ysis of prospectively collected data. These patients Limiting symptoms are revealed in a significant underwent echocardiography and ETT at presen- proportion of patients with apparently asymp- tation, and then most were restudied when their tomatic aortic stenosis (AS) on treadmill exercise AS crossed the threshold between moderate and testing1 2 and are a class I indication for aortic valve severe and thereafter annually. However, 70 (22%) replacement (AVR) according to both American patients with severe AS and risk factors associated and European guidelines.3 4 Conversely, the absence with higher progression rate were assessed every of symptoms on exercise has an excellent negative 6 months.7 predictive value with an approximately 10% rela- Baseline height, weight and seated blood pressure tive risk of developing spontaneous symptoms or were obtained. Hypercholesterolaemia was defined a clinical event within 12 months.5 Furthermore, as treatment with lipid-lowering therapy. Hyperten- To cite: Saeed S, Rajani R, serial testing may add incremental prognostic infor- sion was defined as previously known hypertension, Seifert R, et al. Heart Epub ahead of print: mation to one performed at baseline. In the litera- past or current treatment with antihypertensive [please include Day Month ture, however, no previous study has reported the agents or blood pressure at the baseline clinic visits Year]. doi:10.1136/ results of serial exercise treadmill tests (ETTs) in >140/90 mm Hg.8 All patients with spontaneous heartjnl-2018-312939 patients with moderate or severe AS. Traditionally, or revealed symptoms underwent conventional Saeed S, et al. Heart 2018;0:1–7. doi:10.1136/heartjnl-2018-312939 1 Copyright Article author (or their employer) 2018. Produced by BMJ Publishing Group Ltd (& BCS) under licence. Valvular heart disease coronary angiography prior to surgical or transcutaneous AVR. (LV) wall thicknesses, chamber dimensions, stroke volume and Coronary artery disease was defined as previous myocardial ejection fraction were measured following the joint European Heart: first published as 10.1136/heartjnl-2018-312939 on 13 April 2018. Downloaded from infarction, coronary artery bypass grafting or percutaneous Association of Cardiovascular Imaging and American Society coronary intervention, or angiographic evidence of coronary of Cardiology guidelines.3 4 14 LV hypertrophy was diagnosed artery disease. Most patients were studied prospectively in according to the prognostically validated cut-off values of LV previously reported studies,1 9 10 but the aims and analyses were mass >46.7 g/m2.7 in women and 49.2 g/m2.7 in men, respec- different from this larger analysis. Approval for the study was tively, and relative wall thickness as LV posterior wall thickness/ obtained by local institutional review board (study protocol n. LV internal radius at end-diastole, and considered increased 7461/2017). The study was managed and conducted in accor- if ≥0.430.15 EOA was calculated using the continuity equation dance with the Declaration of Helsinki and latest Good Clinical employing the ratio of subaortic to transaortic systolic velocity Practice guidelines. integral. Exercise testing Study endpoints All ETTs were performed according to American College of Endpoints recorded during follow-up were AVR (either surgical Cardiology/American Heart Association practice guidelines or via a transcatheter approach), all-cause mortality or a using a Bruce protocol modified by two warm-up stages.11 12 composite of AVR and all-cause mortality. Deaths were classified ETT was only done if the patient was asymptomatic on symptom as cardiovascular or non-cardiac and confirmed by reviewing the inquiry. The test was conducted by an exercise physiologist and electronic patient record or a death certificate with censoring either a cardiologist or cardiac nurse. During the test, subjects date 19 September 2017. Follow-up time was calculated from were questioned for symptoms every 2 min, and the haemo- the baseline ETT until AVR, death or censoring. dynamic parameters and a 12-lead ECG are recorded at base- line, at the end of each stage and at peak exercise. The test was Statistical analyses stopped prematurely for symptoms (significant breathlessness SPSS V.24.0 was used for data management and statistical anal- or any chest constriction or dizziness), progressive ventricular yses. Continuous variables were tested for normality of distri- ectopy >3 beats, new atrial fibrillation, a sustained fall in systolic bution and presented as mean±SD, and categorical variables blood pressure >20 mm Hg from the previous stage or more as percentages. Intergroup comparison was performed using than 5 mm ST segment depression. Significant breathlessness Student’s t test or χ2 test, as appropriate. Random slope/inter- was differentiated clinically from physiological breathlessness cept linear mixed effects models with first-order autoregression by the presence of distress, the inability to speak, facial pallor were used to estimate trends in continuous variables of ETT visits and sometimes associated ventricular ectopy or a fall in blood over time. Categorical variables were test with McNemar’s test. pressure. The following were recorded: reason(s) for stopping Survival curves were generated using Kaplan-Meier methods (symptom, fall in blood pressure, ventricular ectopy, ST segment for the endpoints of interest, and groups were compared using depression
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