Open access Valvular heart disease Impact of selected comorbidities on the presentation and management of aortic stenosis Tanja K. Rudolph,1 David Messika-­Zeitoun ‍ ‍ ,2 Norbert Frey,3 Jeetendra Thambyrajah,4 Antonio Serra,5 Eberhard Schulz,6 Jiri Maly,7,8 Marco Aiello,9 Guy Lloyd,10 Alessandro Santo Bortone,11 Alberto Clerici,12 Georg Delle-­Karth,13 Johannes Rieber,14 Ciro Indolfi,15 Massimo Mancone,16 Loic Belle,17 Alexander Lauten,18 Martin Arnold,19 Berto J Bouma,20 Matthias Lutz,3 Cornelia Deutsch,21 Jana Kurucova,22 Martin Thoenes,23 Peter Bramlage ‍ ‍ ,21 Richard P. Steeds24 ►► Additional material is Abstract published online only. To view Key questions Background Contemporary data regarding the impact please visit the journal online of comorbidities on the clinical presentation and (http://​dx.​doi.​org/​10.​1136/​ What is already known about this subject? management of patients with severe aortic stenosis (AS) openhrt-​2020-​001271). ►► Current European guidelines recommend that aortic are scarce. valve replacement (AVR) be performed in patients To cite: Rudolph TK, Methods Prospective registry of severe patients with AS with aortic stenosis (AS) that are symptomatic, ex- Messika-­Zeitoun D, Frey N, et al. across 23 centres in nine European countries. perience symptoms/hypotension during exercise Impact of selected comorbidities Results Of the 2171 patients, chronic kidney disease testing and/or that have a left ventricular ejection on the presentation and (CKD 27.3%), left ventricular ejection fraction (LVEF) <50% management of aortic stenosis. fraction (LVEF) <50%. Contemporary data regarding (22.0%), atrial fibrillation (15.9%) and chronic obstructive Open Heart 2020;7:e001271. the impact of comorbidities on the clinical presen- pulmonary disease (11.4%) were the most prevalent doi:10.1136/ tation and management of patients with severe AS comorbidities (49.3% none, 33.9% one and 16.8% ≥2 of openhrt-2020-001271 are scarce. these). The decision to perform aortic valve replacement (AVR) was taken in a comparable proportion (67%, 72% What does this study add? Received 19 February 2020 and 69%, in patients with 0, 1 and ≥2 comorbidities; ►► IMPULSE is a prospective, multinational registry of Revised 26 March 2020 p=0.186). However, the decision for TAVI was more patients with AS across Europe. The present data Accepted 2 June 2020 common with more comorbidities (35.4%, 54.0% and suggest an overall relationship between the pres- 57.0% for no, 1 and ≥2; p<0.001), while the decision ence of chronic kidney disease (CKD), reduced LVEF, for surgical AVR (SAVR) was decreased with increasing atrial fibrillation and chronic obstructive pulmonary comorbidity burden (31.9%, 17.4% and 12.3%; p<0.001). disease with the presentation of patients with severe The proportion of patients with planned AVRs that were AS and their management. Certain comorbidities performed within 3 months was significantly higher in appear to have more of an influence over treatment patients with 1 or ≥2 comorbidities than in those without decisions, with CKD an apparent deterrent and LVEF (8.7%, 10.0% and 15.7%; p<0.001). Furthermore, the <50% an apparent incentive for AVR. mean time to AVR was significantly shorter in patients with one (30.5 days) or ≥2 comorbidities (30.8 days) than in How might this impact on clinical practice? those without (35.7 days; p=0.012). Patients with reduced ►► The life-­saving AVR- intervention was still denied LVEF tended to be offered an AVR more frequently and in a high proportion of patients, with many of the with a shorter delay while patients with CKD were less planned AVRs not carried out within 3 months. On a frequently treated. more encouraging note, transcatheter aortic valve Conclusions Comorbidities in severe patients with AS implantation was more frequently assigned to co- affect the presentation and management of patients with morbid patients, with such interventions performed © Author(s) (or their severe AS. TAVI was offered more often than SAVR and within a shorter time period. employer(s)) 2020. Re-­use performed within a shorter time period. permitted under CC BY-­NC. No commercial re-­use. See rights and permissions. Published replacement (AVR) face an extremely poor by BMJ. Introduction prognosis; this is particularly true following For numbered affiliations see Aortic stenosis (AS) is the most frequent symptom onset, at which point average end of article. native valve disease worldwide, affecting survival is just 2–3 years.3 Consequently, rapid, approximately 3.4% of elderly individuals in effective management is paramount. Correspondence to Professor Tanja K. Rudolph; ​tk.​ Europe and the USA.1 2 Patients with severe Current European guidelines recommend rudolph@​me.​com AS who do not undergo timely aortic valve that AVR be performed in patients with AS Rudolph TK, et al. Open Heart 2020;7:e001271. doi:10.1136/openhrt-2020-001271 1 Open Heart that are symptomatic, experience symptoms/hypotension Statistics during exercise testing, and/or that have a left ventric- As we aimed to assess the impact of comorbidities on ular ejection fraction (LVEF) <50%.4 However, despite disease presentation and management decisions, we the ever-­growing availability of transcatheter aortic valve described the prevalence of and identified the four implantation (TAVI) as a minimally invasive alternative most prevalent comorbidities. Patients were then strati- to surgical AVR (SAVR), studies suggest that up to 40% of fied according to baseline comorbidity burden. Three patients with severe AS still do not receive either of these groups were built, according to the absence, the presence life-­saving interventions.5–7 The reason for this appears of one or the presence of at least two of the following to be multifactorial, though a high comorbidity burden four comorbidities: LVEF <50%; chronic kidney disease has been suggested as a key driver.8 Furthermore, certain (CKD; defined as creatinine clearance <50 mL/min), comorbidities may have clinical presentations resembling atrial fibrillation (AF; based on physician diagnosis) and those of AS. To the best of our knowledge, no formal chronic obstructive pulmonary disease (COPD; defined investigations into such effects have been carried out to as per EuroSCORE (ES)). Patients were also grouped date. according to the presence/absence of each of these The aim of this analysis therefore was to assess the individual comorbidity types. To serve as a surrogate for impact of comorbidities on disease presentation and overall comorbidity, patients were also divided into those management decisions in patients with severe AS. with/without a high surgical risk score (defined as ES I≥10% and/or ES II≥4%). Data were analysed using descriptive statistics, with continuous variables presented as means with SD and Methods categorical variables as absolute values with percentages. The design and rationale of IMPULSE, a prospective, Comparisons across comorbidity-­ burden groups were multinational registry of patients with AS across Europe, made using analysis of variance or Kruskal-­Wallis test for has been previously described.6 9 Briefly, the study formed continuous and Pearson’s X2 for categorical variables. part of a quality of care initiative combining observa- Comparisons between patients with/without a partic- tional and interventional elements. In total, patients were ular comorbidity type were made using a Pearson’s X2 or enrolled at 23 centres across nine countries (Austria, Fisher’s exact test for categorical variables and a t-­test or Czech Republic, France, Germany, Italy, the Netherlands, Wilcoxon signed-­rank test for continuous variables. The Spain, Switzerland and the UK) up until April 2017; all association between each comorbidity of interest and the sites offered the full range of treatment options for AS. presentation of AS symptoms was explored using univar- Informed consent was obtained prior to patient enrol- iate logistic regression analysis and presented as ORs with ment. 95% CIs. All statistical analyses were performed using SPSS V.24.0 (IBM), with a p<0.05 considered statistically Patients significant. Patients aged at least 18 years that had been referred for echocardiography and were diagnosed with severe AS (defined as aortic valve area (AVA) <1 cm2, indexed Results AVA <0.6 cm2/m2, maximum jet velocity (Vmax) >4 m/s or Of the 2171 patients documented, the mean age was mean transvalvular gradient >40 mm Hg) symptomatic or 77.9 years, 48.0% were female and 80.3% were sympto- asymptomatic were consecutively enrolled. We excluded matic (51.7% severe). The most common comorbidi- patients that had previously undergone AVR. ties were CKD (27.3%), a reduced LVEF <50% (22.0%), AF (15.9%) and COPD (11.4%), representing 50.7% Data collection and definitions (n=1100) of all patients (figure 1). While 1071 patients At baseline, we documented data regarding patient (49.3%) had none of the comorbidities of interest, 735 demographics, medical history and symptoms (chest (33.9%) had one comorbidity, and 365 (16.8%) had two pain, shortness of breath and dizziness on exertion/ comorbidities or more. A high surgical risk defined as an syncope) in an electronic case report form. Angina ES I≥10% and/or ES II≥4% was documented for 42.9% (Canadian Cardiovascular Society class III or IV), New of the patients. York Heart Association (NYHA) class III/IV and dizzi- ness on exertion/syncope were considered severe symp- Comorbidity and as presentation toms. Details of each patient’s AVA, mean AV gradient, When patients were stratified by the number of comor- concomitant mitral/tricuspid regurgitation, LVEF and bidities, there was an increase in age (range mean 75.7 left ventricle dimensions were recorded from their up to 81.4 years), the proportion of severely frail patients echocardiogram. All treatment decisions (TAVI, SAVR, (2.5 up to 10.8%), and the surgical risk (ES II mean 2.2 up balloon aortic valvuloplasty (BAV), watchful waiting and to 8.2%) (table 1). Furthermore, mitral (mean 5.2 up to active decision not to treat) were documented. All data 20.4%) as well as tricuspid (3.9 up to 18.9%) regurgitation were subject to automatic checks for plausibility and was more prevalent. Similar trends were observed when completeness. comparing patients without a particular comorbidity of 2 Rudolph TK, et al. Open Heart 2020;7:e001271. doi:10.1136/openhrt-2020-001271 Valvular heart disease symptomatic patients only with 41.8%, 57.4% and 58.8% of patients being assigned to TAVI and 36.5%, 18.0% and 13.0% being assigned to SAVR (p<0.001). An active deci- sion not to treat (5.8%, 9.5% and 12.6%; p<0.001) was more frequently chosen in those with a higher comor- bidity burden. The proportion of patients with planned AVRs that were performed within 3 months was significantly higher in patients with one or at least two comorbidities than in those with no comorbidities (15.7%, 10.0% and 8.7% respectively; p<0.001) (figure 2). This was mostly observed based on the rates of non-­ performance in patients scheduled to undergo surgery and none of the comorbidities of interest (p<0.001), while there was no such trend among patients scheduled for TAVI. Figure 1 Prevalence of comorbidities. AF, atrial fibrillation; Furthermore, the mean time to AVR was significantly CKD, chronic kidney disease; COPD, chronic obstructive shorter in patients with one (30.5±33.6) or at least two pulmonary disease; LVEF, left ventricular ejection fraction; comorbidities (30.8±32.3 days) than in those without light blue bars, those considered for the comorbidity burden (35.7±36.1 days; p=0.012 across groups) (table 1). in dark blue; green bars, those not considered for the comorbidity burden in dark blue. Treatment decisions according to comorbidity type The decision to perform AVR was taken in comparable proportions of patients with and without AF, and those interest to those with the particular comorbidity (online with and without COPD. This choice was, however, signif- supplementary tables 1–5). One exception was gender; icantly more frequent in patients with an LVEF ≤50% compared with patients without the respective comor- compared with those with an LVEF >50% (78.3% vs bidity, females were more common among patients with 66.4%; p<0.001) and significantly less frequent in those CKD (55.6% vs 45.1%; p<0.001), while males were more with CKD compared with those without CKD (65.1% vs common among those with an LVEF <50% (63.6% vs 71.4%; p=0.011) (figure 2). In general, TAVI was a more 49.1%; p<0.001). common treatment choice in patients with compared The proportion of patients with any symptoms (73.6%, with without each of the comorbidities of interest, with 84.4%, 91.8%; p<0.001) and severe symptoms (40.8%, the inverse true for SAVR. 58.4% and 70.1%; p<0.001) increased alongside comor- Performance of a planned AVR within 3 months of the bidity burden (table 1). Furthermore, each of the single treatment decision was more common in patients with comorbidities of interest was significantly associated with an LVEF ≤50% compared with those with an LVEF >50% a greater likelihood of being symptomatic (table 2). (68.1% vs 53.4%; p<0.001). The mean time to AVR was Reduced EF and COPD were strongly associated with any significantly shorter in patients with CKD compared with as well as severe symptoms (OR >2.0) while there was a those without this condition (29.0±29.2 vs 34.3±35.7; lesser association of CKD and AF with any symptom class p=0.013) (online supplementary tables 1–5). These (OR >1.0 to<2.0). Of note, a high ES was associated with trends were not observed for AF or COPD. symptoms throughout all domains whether it be any (OR 2.55; 95% CI 1.9 to 3.31) or severe (OR 2.27; 95% CI Discussion 1.88 to 2.74) symptoms and the only who was associated In our contemporary cohort of patients with severe AS, with chest pain (OR 1.66; 95% CI 1.33 to 2.07). So both, renal impairment, impaired LV function, AF and COPD general and cardiac presentation were worse in patients were common. Each was found to be associated with with comorbidities. (severe) symptoms. Though the number of comorbidities did not appear to affect the overall decision to perform Treatment decisions according to comorbidity burden AVR, TAVI was more frequently assigned to patients with The decision to perform AVR was taken in compa- more comorbidities, with interventions being performed rable proportions of patients, regardless of comorbidity within a shorter time period. Specifically, CKD appeared burden (69.0% overall), with 31% not assigned to AVR to be a deterrent for AVR, with LVEF ≤50% an apparent (figure 2). However, the decision to perform TAVI was incentive. Overall, nearly one-­ third of patients were more common in patients with a greater number of not assigned to undergo life-­saving AVR, with this value comorbidities (35.4%, 54.0% and 57.0% for patients being as high as 35% in patients with CKD in the present with no, one and at least two comorbidities, respectively; registry. p<0.001 across groups), while the decision for SAVR was decreased with increasing comorbidity burden (31.9%, Comorbidity burden 17.4%, and 12.3%; p<0.001 across groups). The same Approximately half of the patients with severe AS trends were observed when the analysis was confined to enrolled in the IMPULSE registry had one or more of the Rudolph TK, et al. Open Heart 2020;7:e001271. doi:10.1136/openhrt-2020-001271 3 Open Heart Table 1 Baseline patient characteristics, echocardiographic parameters and treatment decisions by number of comorbidities P value across All patients 0 comorbidities* One comorbidity* ≥2 comorbidities* comorbidity (n=2171) (n=1071) (n=735) (n=365) groups Age (years) 77.9±10.0 75.7±10.7 79.4±9.0 81.4±7.8 <0.001 Female gender 48.0 48.0 50.2 43.3 0.097 Severe frailty† 5.1 2.5 6.1 10.8 <0.001 EuroSCORE I (%) 15.6±13.9 9.5±8.2 17.9±12.8 26.8±18.5 <0.001 EuroSCORE II (%) 4.0±5.0 2.2±3.0 4.7±4.7 8.2±7.2 <0.001 Echocardiographic valve         parameters  Indexed AV area (cm2/m2) 0.40±5.0 0.41±0.11 0.39±0.10 0.37±0.11 <0.001  Mean AV gradient (mm 47.1±14.7 50.0±13.3 45.4±14.8 42.2±16.3 <0.001 Hg)  Mitral regurgitation grade 10.7 5.2 13.6 20.4 <0.001 III/IV  Tricuspid regurgitation 7.9 3.9 8.1 18.9 <0.001 grade III/IV  Indexed LV mass (g/m2) 132.6±40.9 126.7±38.0 134.4±41.1 147.6±44.7 <0.001 Symptomatic status‡ (%) 80.3 73.6 84.4 91.8 <0.001 Severe symptomatic status§ 51.7 40.8 58.4 70.1 <0.001 (%) Decision to perform AVR 69.0 67.2 71.5 69.3 0.186  AVR performed within 56.3 51.5 61.5 60.5 <0.001 3 months  Time to intervention (days) 33.0±34.7 35.7±36.1 30.5±33.6 30.8±32.3 0.012 Decision to perform TAVI 45.0 35.4 54.0 57.0 <0.001  TAVI performed within 38.0 28.3 47.0 50.5 <0.001 3 months  Time to intervention (days) 29.2±34.2 30.0±36.4 29.2±33.6 27.5±31.0 0.755 Decision to perform SAVR 24.0 31.9 17.4 12.3 <0.001  SAVR performed within 18.3 23.3 14.4 10.0 <0.001 3 months  Time to intervention (days) 40.7±34.5 42.4±34.7 34.5±33.4 46.5±34.4 0.037 Decision not to perform AVR 27.6 29.1 25.7 26.5 <0.001 *LVEF <50%, CKD, AF or COPD. †Defined as an inability to walk 5 m in ≤6 s and/or to perform activities of daily living.24 ‡Defined as chest pain, shortness of breath and/or dizziness on exertion/syncope. §Defined as CCS class III or IV angina, NYHA class III/IV and/or dizziness on exertion/syncope. AF, atrial fibrillation; AV, aortic valve; AVA, aortic valve area; AVR, aortic valve replacement; CCS, Canadian Cardiovascular Society; CKD, chronic kidney disease ; COPD, chronic obstructive pulmonary disease; LV, left ventricular; LVEF, left ventricular ejection fraction; NYHA, New York Heart Association; SAVR, surgical AVR; TAVI, transcatheter aortic valve implantation . comorbidities of interest, with a sixth having two or more. alongside increasing comorbidity burden is unsurprising. In line with the observations of prior studies, those with Nevertheless, the decision to perform AVR was taken a greater number of comorbidities were older and more in a similar proportion of patients with 0, 1 or at least 2 commonly frail.10 They also had worse left ventricular comorbidities. function accompanied by lower AV gradients but smaller This likely reflects a balance between the lower disease indexed effective orifice area, indicating a certain propor- severity in patients with fewer comorbidities, increasing tion of patients with ‘low-­gradient’ AS.11 The predictive the tendency towards watchful waiting, and the deterring value of effective orifice area and LV parameters for influence of a higher age and greater surgical risk in symptom onset has been previously reported.12 13 As such, those with a higher comorbidity burden, increasing the observed increase in the prevalence of symptoms the frequency of decisions not to treat the patient or to 4 Rudolph TK, et al. Open Heart 2020;7:e001271. doi:10.1136/openhrt-2020-001271 Valvular heart disease Table 2 Association of the most frequent comorbidities with AS symptoms and severity CKD Low LVEF AF COPD High ES (n=2171) (n=1071) (n=735) (n=365) (n=795) Symptomatic status 1.99 (1.50–2.65) 2.58 (1.85–3.58) 1.45 (1.04–2.02) 2.85 (1.80–4.52) 2.55 (1.97–3.31)  Chest pain 1.10 (0.87–1.39) 1.25 (0.98–1.59) 0.98 (0.73–1.31) 1.26 (0.92–1.73) 1.66 (1.33–2.07)  Shortness of breath 1.91 (1.49–2.46) 2.99 (2.20–4.05) 1.53 (1.13–2.07) 3.25 (2.12–4.97) 2.53 (2.01–3.19)  Dizziness/syncope 1.19 (0.93–1.51) 1.53 (1.20–1.97) 1.33 (1.00–1.77) 1.49 (1.09–2.05) 1.48 (1.19–1.85) Severe symptomatic status* 1.98 (1.62–2.44) 2.39 (1.92–2.98) 1.49 (1.17–1.90) 2.06 (1.56–2.73) 2.27 (1.88–2.74)  Angina class III/IV 2.33 (1.47–3.70) 1.58 (0.98–2.55) 0.94 (0.50–1.75) 1.46 (0.80–2.69) 2.13 (1.34–3.40)  NYHA class III/IV 2.26 (1.85–2.78) 2.77 (2.23–3.44) 1.43 (1.12–1.83) 2.34 (1.78–3.08) 2.67 (2.20–3.24) *Includes dizziness/syncope, as listed under symptomatic status. AF, atrial fibrillation; CKD, chronic kidney disease; COPD, chronic obstructive pulmonary disease; ES, EuroSCORE; LVEF, left ventricular ejection fraction; NYHA, New York Heart Association. perform BAV instead. Given that guidelines recommend against the performance of AVR in patients with severe comorbidities when it is unlikely to improve quality of life or survival,4 the latter trend may be appropriate. However, the observed reluctance to perform AVR in one-­third of patients with none of the comorbidities of interest, who had severe AS and a less-­than-­high surgical risk may indicate a tendency towards undertreatment.4 Even in the subset of these latter patients that were assigned to AVR, nearly a quarter did not undergo the procedure within 3 months. Furthermore, the overall rate of patients denied AVR was approximately comparable to that reported by the Euro Heart Survey in 2005, before the advent of TAVI. Encouragingly, TAVI was assigned more often to patients with higher comorbidity burdens, with more SAVR planned in those with fewer comorbid- ities. This is in line with current guidelines,4 and reflects the widespread recognition of TAVI as a safer alternative to SAVR in patients at higher surgical risk. Chronic kidney disease CKD was a highly prevalent comorbidity in the IMPULSE population, affecting over a quarter of patients. In addi- tion to predicting overall symptomatic or severe sympto- matic status, CKD was the only comorbidity of interest that was significantly associated with angina class III/IV. The relationship between renal impairment and coro- nary artery disease (CAD) is well established, explained by their numerous shared risk factors.14 However, the principal mechanism underlying angina in AS is increased left ventricular demand, rather than coronary artery stenosis.15 Consequently, angina may have been Figure 2 Treatment decision by number and type of interpreted as a symptom of CAD in patients with CKD, comorbidities. P<0.001 for TAVI planned overall, SAVR rather than of AS. Whether right or wrong, this is likely planned overall and no AVR planned overall; p<0.001 for to have impacted on treatment decision; speculatively, it AVR planned but not performed and SAVR planned is possible that some patients with CKD may have been but not performed; †ES I ≥10% or ES II ≥4%. *P<0.05; denied TAVI due to misattribution of AS-­related angina **p<0.01; ***p<0.001. AF, atrial fibrillation; AVR, aortic valve symptoms to CAD. This merits further investigation. replacement; BAV, balloon aortic valvuloplasty; CKD, chronic kidney disease; COPD, chronic obstructive pulmonary CKD appeared to be a deterrent for AVR, which was disease; LVEF, left ventricular ejection fraction; ES, assigned significantly less frequently in patients with this EuroSCORE; SAVR, surgical aortic valve replacement; TAVI, comorbidity. The observed trend may be justified in the transcatheter aortic valve implantation; context of the aforementioned benefit considerations Rudolph TK, et al. Open Heart 2020;7:e001271. doi:10.1136/openhrt-2020-001271 5 Open Heart stipulated by guidelines.4 Regardless, a striking prefer- Atrial fibrillation ence for TAVI over SAVR was evident in CKD patients, Though AF was a fairly common comorbidity among with only 15% of those scheduled for AVR assigned to IMPULSE patients, it appeared to have very little influ- SAVR. There is clear evidence that TAVI patients have ence on the presentation and management of severe AS. higher rates of all-­cause mortality and major cardiac/ This may be surprising, given that AF has been associated cerebrovascular events, while the SAVR patients had a with a higher risk of all-­cause and cardiac mortality in higher risk of dialysis. Thus, the decision to perform patients undergoing TAVI.21 22 However, a recent study any type of AVR in patients with CKD must be made suggests that the protective effect of AVR is relatively with extreme caution, with distinct risks associated stronger in patients with AF than in those with normal with the surgical and transcatheter interventions. The sinus rhythm.23 Thus, it is reasonable that the comor- appropriacy of the strong preference for TAVI in the bidity is not a direct deterrent. present patients with CKD requires further investiga- tion, though this treatment decision might be mainly Limitations driven by the strikingly high ES values recorded in this The major limitation of the present analysis was the lack subset. of adjustment for confounding factors, including other comorbidities that may have influenced AS presentation Left ventricular ejection fraction and treatment decisions. As such, unequivocal identifi- Just over a fifth of patients had an LVEF <50%. In line with cation of independent associations between the comor- previously reported trends, a larger proportion of these bidities of interest and symptoms/management strate- gies is problematic. Nevertheless, the consistency of the were male.16 As with the other comorbidities of interest, observed trends with published data and clinical logic a reduced LVEF was predictive of overall symptomatic supports the value of our findings, which form a strong status, shortness of breath and NYHA class III/IV, but basis for further exploration. was also one of the only comorbidities specifically predic- tive for dizziness on exertion/syncope. This is consistent with the idea that patients with impaired LVEFs are Conclusions less tolerant to rapid heart rhythms.17 Given that LVEF The present data suggest an overall relationship between <50% is an independent criterion for AVR according to the presence of CKD, reduced LVEF, AF and COPD with European guidelines,4 it is no surprise that the choice the presentation of patients with severe AS and their to perform AVR was significantly more common in management. Certain comorbidities appear to have more patients with a low compared with a preserved LVEF. of an influence over treatment decisions, with CKD an These individuals were also assigned to TAVI much more apparent deterrent and LVEF<50% an apparent incen- frequently with this decision reinforced by the increased tive for AVR. However, this life-­saving intervention was surgical risk and by the evidence for a more rapid and still denied in a high proportion of patients, with many complete recovery of LV function after TAVI compared of the planned AVRs not carried out within 3 months. with SAVR.18 As such, LVEF appears to have a strong and On a more encouraging note, TAVI was more frequently logical influence on both AS symptoms and treatment assigned to comorbid patients, with such interventions decisions. performed within a shorter time period. Chronic obstructive pulmonary disease Author affiliations 1 COPD was present in approximately 11% of patients. Department of Cardiology, Heart and Diabetes Center Bad Oeynhausen, Ruhr-­ University of Bochum, Bad Oeynhausen, Germany While the majority of the trends in patient characteristics 2 University of Ottawa Heart Institute, Ottawa, Ontario, Canada across increasing comorbidity burdens were also observed 3 Department of Cardiology and Angiology, University of Kiel, Kiel, Germany for patients without compared with with COPD, the values 4 James Cook University Hospital, Middlesbrough, UK 5 for echocardiographic parameters were strikingly similar Interventional Cardiology Unit, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain between these two subsets, indicating similar AS stages. 6 Cardiology Department, AKH Celle, Celle, Germany This similarity is largely consistent with another study that 7 Department of Cardiovascular Surgery, Institute for Clinical and Experimental reported baseline data for patients with AS stratified by Medicine, Prague, Czech Republic the presence/absence of COPD.19 As such, the observed 8 Department of Cardiovascular Surgery, Second Faculty of Medicine, Charles higher likelihood of dizziness on exertion/syncope asso- University, Prague, Czech Republic 9 Department of Cardiothoracic Surgery, Foundation IRCCS Policlinico S.Matteo, ciated with COPD is probably attributable to the lung Pavia, Italy disease itself, rather than as a direct consequence of AS.20 10 St Bartholomew's Hospital, London, UK Furthermore, the fact that AVR was performed in approx- 11 University of Bari, Bari, Italy 12 imately equivalent proportions of patients with/without University of Turin, Turin, Italy 13 COPD may also be explained by largely comparable heart 4th Medical Department, Hietzing Hospital, Vienna, Austria 14 Herzkatheterlabor Nymphenburg and Department of Cardiology, University of disease states. Nevertheless, TAVI was again favoured in Munich, Munich, Germany patients with COPD, consistent with the higher overall ES 15 Division of Cardiology and URT CNR of IFC, Magna Graecia University, Catanzaro, in those with this comorbidity. Italy 6 Rudolph TK, et al. Open Heart 2020;7:e001271. doi:10.1136/openhrt-2020-001271 Valvular heart disease 16 Sapienza University of Rome, Rome, Italy 4 Baumgartner H, Falk V, Bax JJ, et al. 2017 ESC/EACTS guidelines 17 Centre Hospital d’Annecy, Annecy, France for the management of valvular heart disease. Eur Heart J 18 German Centre for Cardiovascular Research (DZHK), University Heart Center & 2017;38:2739–91. 5 Malaisrie SC, Tuday E, Lapin B, et al. Transcatheter aortic valve Charité, Berlin, Germany implantation decreases the rate of unoperated aortic stenosis. Eur J 19 Department of Cardiology, University of Erlangen, Erlangen, Germany Cardiothorac Surg 2011;40:43–8. 20 University of Amsterdam, Amsterdam, Netherlands 6 Frey N, Steeds RP, Rudolph TK, et al. Symptoms, disease severity 21 Institute for Pharmacology and Preventive Medicine, Cloppenburg, Germany and treatment of adults with a new diagnosis of severe aortic 22 Edwards Lifesciences, Prague, Czech Republic stenosis. Heart 2019;105:1709–16. 23 7 Steeds RP, Lutz M, Thambyrajah J, et al. Facilitated data relay and Edwards Lifesciences, Nyon, Switzerland 24 effects on treatment of severe aortic stenosis in Europe. J Am Heart Queen Elizabeth Hospital & Institute of Cardiovascular Sciences, University of Assoc 2019;8:e013160. Birmingham, Birmingham, UK 8 Bach DS, Siao D, Girard SE, et al. Evaluation of patients with severe symptomatic aortic stenosis who do not undergo aortic Twitter Richard P. Steeds @Richard.Steeds valve replacement: the potential role of subjectively overestimated operative risk. Circ Cardiovasc Qual Outcomes 2009;2:533–9. Acknowledgements Data were captured using the s4trials Software provided by 9 Frey N, Steeds RP, Serra A, et al. Quality of care assessment Software for Trials Europe, Berlin, Germany. and improvement in aortic stenosis - rationale and design of a multicentre registry (IMPULSE). BMC Cardiovasc Disord 2017;17:5. Contributors NF, RPS, DM-­Z, JK, MT and PB were involved in the conception 10 Fukui S, Kawakami M, Otaka Y, et al. Physical frailty in older people and design of the study. PB and TKR drafted the manuscript and all other authors with severe aortic stenosis. Aging Clin Exp Res 2016;28:1081–7. revised the article for important intellectual content. All authors gave final approval 11 Clavel M-­A, Magne J, Pibarot P. Low-­gradient aortic stenosis. Eur of the version. Heart J 2016;37:2645–57. 12 Dalsgaard M, Kjaergaard J, Pecini R, et al. Predictors of exercise Funding This work was supported with a research grant provided by Edwards capacity and symptoms in severe aortic stenosis. Eur J Echocardiogr Lifesciences (Nyon, Switzerland). 2010;11:482–7. Competing interests PB is the representative of the IPPMed, Cloppenburg, 13 Takeda S, Rimington H, Chambers J. Prediction of symptom-­onset in aortic stenosis: a comparison of pressure drop/flow slope and Germany. NF, RPS, DM-­Z and TKR are consultants to Edwards Lifesciences. The haemodynamic measures at rest. Int J Cardiol 2001;81:131–7. institutions of these three and those of the remaining authors representing study 14 Briasoulis A, Bakris GL. Chronic kidney disease as a coronary artery centres have received funding for employing a study nurse. disease risk equivalent. Curr Cardiol Rep 2013;15:340. Patient consent for publication Not required. 15 Fallen EL, Elliott WC, Gorlin R. Mechanisms of angina in aortic stenosis. Circulation 1967;36:480–8. Ethics approval The study was carried out in accordance with the Declaration 16 Fuchs C, Mascherbauer J, Rosenhek R, et al. Gender differences in of Helsinki and was approved by the independent ethics review board at each clinical presentation and surgical outcome of aortic stenosis. Heart participating institution. 2010;96:539–45. 17 Arnar DO. Syncope in patients with structural heart disease. J Intern Provenance and peer review Not commissioned; externally peer reviewed. Med 2013;273:336–44. Data availability statement Data are available on reasonable request. Data are 18 Bauer F, Coutant V, Bernard M, et al. Patients with severe aortic stenosis and reduced ejection fraction: earlier recovery available on reasonable request from the corresponding author. of left ventricular systolic function after transcatheter aortic Open access This is an open access article distributed in accordance with the valve implantation compared with surgical valve replacement. Creative Commons Attribution Non Commercial (CC BY-­NC 4.0) license, which Echocardiography 2013;30:865–70. permits others to distribute, remix, adapt, build upon this work non-­commercially, 19 Mok M, Nombela-­Franco L, Dumont E, et al. Chronic obstructive pulmonary disease in patients undergoing transcatheter aortic valve and license their derivative works on different terms, provided the original work is implantation: insights on clinical outcomes, prognostic markers, and properly cited, appropriate credit is given, any changes made indicated, and the use functional status changes. JACC Cardiovasc Interv 2013;6:1072–84. is non-­commercial. See: http://​creativecommons.​org/​licenses/​by-​nc/​4.​0/. 20 Roberts MM, Cho J-­G, Sandoz JS, et al. Oxygen desaturation and adverse events during 6-­min walk testing in patients with COPD. ORCID iDs Respirology 2015;20:419–25. David Messika-­Zeitoun http://​orcid.​org/​0000-​0002-​6278-​5670 21 Tarantini G, Mojoli M, Windecker S, et al. Prevalence and Impact of Peter Bramlage http://​orcid.​org/​0000-​0003-​4970-​2110 Atrial Fibrillation in Patients With Severe Aortic Stenosis Undergoing Transcatheter Aortic Valve Replacement: An Analysis From the SOURCE XT Prospective Multicenter Registry. JACC Cardiovasc Interv 2016;9:937–46. References 22 Stortecky S, Buellesfeld L, Wenaweser P, et al. Atrial fibrillation 1 Osnabrugge RLJ, Mylotte D, Head SJ, et al. Aortic stenosis in and aortic stenosis: impact on clinical outcomes among patients the elderly: disease prevalence and number of candidates for undergoing transcatheter aortic valve implantation. Circ Cardiovasc transcatheter aortic valve replacement: a meta-­analysis and Interv 2013;6:77–84. modeling study. J Am Coll Cardiol 2013;62:1002–12. 23 Moretti M, Fabris E, Morosin M, et al. Prognostic significance of atrial 2 Iung B, Baron G, Butchart EG, et al. A prospective survey of patients fibrillation and severity of symptoms of heart failure in patients with with valvular heart disease in Europe: the Euro heart survey on low gradient aortic stenosis and preserved left ventricular ejection valvular heart disease. Eur Heart J 2003;24:1231–43. fraction. Am J Cardiol 2014;114:1722–8. 3 Ramaraj R, Sorrell VL. Degenerative aortic stenosis. BMJ 24 Katz S, Downs TD, Cash HR, et al. Progress in development of the 2008;336:550–5. index of ADL. Gerontologist 1970;10:20–30. Rudolph TK, et al. 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