Quality of Life Measures in Aortic Stenosis Research: A Narrative Review Free

Aortic stenosis (AS) is the most common valvular heart condition and one of the very common causes of morbidity and mortality in elderly patients [1]. As the disease progresses and symptoms develop, prognosis worsens significantly. The implantation of a new valve has been shown to significantly improve prognosis, including improved functional status and lower mortality rates [2]. In addition, treatment goals target the need to improve patient’s quality of life (QoL), which includes increased physical activity, safety, and comfort in daily life. Therefore, it is important to understand which factors contribute to a better patient recovery and QoL [3].

In general terms, QoL in health research refers to a multidimensional construct that includes physical, mental, and social domains and the ability to perform everyday activities including the social and occupational aspects of a patient’s life [4]. Both surgical aortic valve replacement and transcatheter aortic valve implantation (TAVI) have been shown not only to increase survival in patients with severe symptomatic AS but also to improve their QoL [5‒7]. Poor QoL has been associated with increased subsequent hospitalization and higher mortality rates [8]. Therefore, the evaluation of QoL has become an increasingly important component in the assessment of the patient’s experience of an intervention for valvular heart disease in current clinical practice. The reported QoL outcomes help patients and clinicians to make better decisions about the treatment and stimulate healthcare providers to provide better service [9].

To date, various instruments have been developed to evaluate QoL in patients with AS before and after therapeutic interventions. These tools can be categorized into generic and specific instruments: generic QoL scales globally assess physical, psychological, social, functional, and well-being domains without documenting the impact of a particular disease [10]. Such scales are, therefore, useful when QoL shall be compared across a wide range of populations and interventions. Specific scales, on the other hand, focus on a group of diseases or a single disease and are relevant, especially in the context of a specific intervention or a subpopulation [10]. In cardiovascular research, both generic and specific QoL questionnaires are, therefore, often used in studies simultaneously [4].

Although psychometric assessment with QoL instruments and patient-reported outcome measures has become common today, consent on which instrument to use in routine clinical practice of AS treatments is lacking. While several comprehensive reviews of QoL instruments in patients with heart failure are available, we have not found any review of the tools used specific for patients with AS [11, 12]. The objective of this article was to provide an overview of the available QoL instruments in AS research, describe their strengths and weaknesses, and provide our assessment of the utility of available scoring instruments for QoL measurements in AS.

The QoL instruments presented in this review were identified by reviewing publications on QoL in AS patients. The search was conducted on PubMed, February 15, 2023, using “aortic valve stenosis” in combination with “quality of life” (title) as major medical subheading (MeSH) terms. Inclusion was restricted to the studies that included human subjects and were published in English. Titles were checked to exclude unrelated or duplicated articles. Systematic reviews, letters, commentaries, editorials, guidelines, surveys, and case reports were excluded from the review. A list of available QoL tools based on the retained and reviewed publications was created (Table 1). Further, an additional search was done to obtain detailed information regarding each instrument in the list by searching the official websites of the instrument or identifying the original development and validation study of the tool.

The PRISMA diagram shows the search results, screening, and reasons for exclusion of studies (Fig. 1). The search resulted in 124 publications, of which 20 were in a language other than English and were, therefore, excluded. No full-text was found for 8 studies and those studies were excluded as well. Screening of abstracts of the remaining 96 articles revealed that 6 were systematic reviews, 5 had an inadequate description of scales, 4 were duplicates, 1 was not related to AS, and 1 included a hypothetical cohort. The final review included 79 studies that were published that examined QoL in patients with AS. Online supplementary Table 1 (for all online suppl. material, see https://doi.org/10.1159/000531465) presents a summary of the reviewed studies, including center status, study design, sample size, and implemented QoL measure(s) [23‒88]. After a careful revision, a total of 7 QoL instruments were identified: 3 generic and 6 disease-specific. The instruments included in this review are the 3 generic questionnaires Short Form Health Survey (SF-36/SF-12), EuroQol-5D (EQ-5D), and the Illness Intrusiveness Rating Scale (IIRS). The 5 more disease-specific questionnaires include the HeartQoL, the Kansas City Cardiomyopathy Questionnaire (KCCQ), the Minnesota Living with Heart Failure Questionnaire (MLHF), the MacNew Questionnaire, and the Toronto Aortic Stenosis Quality of Life Questionnaire (TASQ). A summary of the main characteristics of the reviewed QoL measures is presented in Table 1.

Short Form Health Survey (SF-36/SF-12) is a generic QoL questionnaire which was developed as part of the Medical Outcomes Study and is used to collect information about the individual’s multidimensional health concepts [13]. Based on the reviewed studies, this questionnaire is the most widely used generic measure for the evaluation of the influence of AS and its treatment on the QoL of patients. The initial version consisted of 149 questions grouped into 16 categories.

In the SF-36, items were reduced to 36, grouped into eight health domains: physical functioning, social functioning, role limitations (physical problems), role limitations (emotional problems), mental health, energy/vitality, bodily pain, and general health and a single item concerning health change. Together, the eight domains comprise two general scores representing the physical and mental aspects of QoL. The SF-36 questionnaire is self-administered and takes approximately 15 min to complete.

The abbreviated form of SF-36, the SF-12, is a shortened version that includes 12 items of the original SF-36 survey that measure each of the eight domains [14]. The SF-12 was designed to predict the physical components summary and mental components summary scores, capturing 90% of the original SF-36 survey’s reach with only one-third of questions [14]. Several studies have indicated no difference between the 12- and 36-item surveys in evaluating patients’ health status, suggesting that the SF-12 should be the primary choice [89, 90]. The results of a study that included 2,441 cardiac rehabilitation patients from 18 centers in Germany demonstrated that the SF-12 similarly estimated the SF-36 physical components summary and mental components summary scores and both questionnaires had similar responsiveness to change [17]. Both SF-36 and SF-12 have been used in conjunction with disease-specific questionnaires [24, 91‒96]. Unlike SF-36, SF-12 can be completed in 1 min. Ultimately, the SF-36 provides more details on individual QoL domains, whereas the SF-12 version can be used by researchers and clinicians looking for a valid but brief QoL measure. Both short and long versions of the questionnaire can be found at the RAND Corporation’s website (https://www.rand.org/health-care/surveys_tools/mos.html).

The main advantages of SF-36/SF-12 include good internal coherence and short completion time. They also incorporate a number of general questions related to emotional and psychological problems associated with poor health and capture some information regarding exercise capacity, which is very relevant in the context of AS. The questionnaires have been thoroughly validated and evaluated and can be applied in a wide range of clinical settings. In addition, the questionnaires are found to be psychometrically and clinically consistent [97].

The generic nature of SF-36/SF-12 can also be disadvantageous when used in specific populations or diseases, including AS as it is not equipped to separate the effects of the AS from those of other conditions. This is of particular concern in AS as most patients present with comorbidities and problems associated with frailty. The SF-36/SF-12 can/should be used for research in AS as a secondary measure in parallel to other disease-specific assessment tools.

EuroQol-5D (EQ-5D) is an internationally recognized generic health-related QoL questionnaire developed by the EuroQol group [15, 98]. It measures patients’ health using 5 dimensions: mobility, self-care, usual activities (work, house chores, study, leisure, and family), anxiety/depression, and pain/discomfort. Each dimension includes three ordinal categories of severity corresponding to no, moderate, or severe problems. Self-classification responses are converted into a single index score which makes the EQ-5D practical for clinical and economical analyses [98]. The index-based score is interpreted along a scale where 1 represents “perfect health” and 0 represents “dead,” with some health states being considered worse than dead (<0). The questionnaire also includes the visual analog scale (VAS) for global assessment of health status, where patients place their current health state on a range from 0 (worst imaginable health state) to 100 (best imaginable health state).

The original EQ-5D included 3 response levels (level 1, representing no problems; level 2, reflecting small or moderate problems; and level 3, indicating extreme problems) and is commonly abbreviated as EQ-5D-3L. However, a revised version with 5 response levels (EQ-5D-5L) was developed to address the issues of the ceiling effect (high proportion of participants reporting “no problems” on one or all dimensions) and low responsiveness to changes in health compared with other preference-based measures [99]. Due to its simple administration and interpretation, the use of the EQ-5D for measuring patient QoL in cardiovascular research has increased in the past decades [100, 101]. In AS research, the EQ-5D has been primarily used as a sole measurement tool, although several studies have used it in combination with other QoL scales (either generic or disease-specific) [24, 95, 64, 91, 102‒105]. All versions of the questionnaire can be accessed at EuroQol.org.

The EQ-5D is a simple and flexible QoL instrument with good reliability and reproducibility [106]. It can also generate outcomes that reflect the societal preference (also called “utilities”) for specific health states, which can be used to calculate quality-adjusted life years (QALY) in health economic analyses [100]. The questionnaire has been translated into more than 200 languages and is available in over 90 countries. EQ-5D can be used to compare health across different types of patients, diseases, and treatments by providing a common metric.

Due to its generic design, EQ-5D should be used concurrently with other disease-specific instruments when assessing QoL in patients with AS. It can be used to collect secondary information which can then be correlated to a disease-specific score. In addition, the questions in the questionnaire are referring to the patient’s health state at the current moment (“today”), which limits its ability to capture episodic symptoms. Comorbidity and general aging can also influence EQ-5D score when it is used during longer periods, which may make it difficult to interpret the effects of treatment and disease progression on the score.

The Illness Intrusiveness Rating Scale (IIRS) is a self-reported QoL instrument that measures the extent to which disease and/or treatment interfere with psychologically meaningful activities in various life domains [107]. The IIRS consists of 13 items and can be scored to generate a total score or three subscale scores: relationships and personal development (health, work, active recreation, passive recreation, and financial situation), intimacy (relationship with partner and sex life), and instrumental (family relations, other social relations, self-improvement/self-expression, religious expression, and community and civic involvements) [107]. The item measuring diet is included in the total score but not in any of the subscales due to factor-analytic inconsistencies [107]. Scores range from 13 to 31, with high scores representing high levels of illness intrusiveness. The instrument can be self-administered or administered by a trained interviewer.

The IIRS was initially developed for patients with end-stage renal disease but has since been used in diverse patient populations [107, 18]. The scale has shown strong psychometric characteristics in chronic disease patients, such as responsiveness to change following the treatment [107]. The IIRS has been implemented only in 1 study with AS patients, where the scale was used to test the validity of another scale [23].

The IIRS is brief, easy to administer, and can be easily understood by patients of all literacy levels. Research has shown that the IIRS can also be self-administered online without compromising reliability or biasing results, which makes it accessible to patients with limited physical ability [107]. The IIRS was initially developed for people affected by chronic disabling and/or life-threatening diseases but can also be administered to those with less severe conditions. The scale is free to use without permission.

Due to the fact that the IIRS has currently been used only in one study focusing on AS patients, the psychometric properties of the scale in this patient population are still unknown. In addition, the IIRS measures general domains not considering the impact of AS-specific symptoms and treatment on patient QoL. Another limitation of the IIRS is that it has been translated only into 6 languages, which limits its use in various countries and cultures.

The HeartQoL was developed and validated in five global regions with a total of 22 countries and 15 languages [16, 17]. It comprises 14 items from the Seattle Angina Questionnaire (SAQ) [108], the MacNew Heart Disease Health-Related Quality of Life Questionnaire (MacNew) [109], and the Minnesota Living with Heart Failure Questionnaire (MLHFQ) [20]. The questionnaire can be divided into 10 items of a physical subscale and 4 items of an emotional subscale. All items on the physical and the emotional subscale are answered on a 4-point scale ranging from “bothered a lot” (= 0) to “not bothered” (= 3). Higher values represent better QoL.

The questionnaire has demonstrated reliability, validity, and partially responsiveness in patients with angina, myocardial infarction, and ischemic heart failure [17, 110, 111]. The HeartQoL in Danish language was also assessed in patients with atrial fibrillation and implantable cardioverter defibrillator [112, 113]. Further it was also used in patients undergoing heart valve surgery, where it demonstrated acceptable construct validity, internal consistency, and test-retest reproducibility [114].

The HeartQoL is a short, 14 item questionnaire that has been developed in patients with heart disease (myocardial infarction, angina, and heart failure). It allows a valid comparison between different cardiac etiologies. Furthermore, it has extensive normative data.

On the other hand, the HeartQoL has, at present, only been validated for patients undergoing heart valve surgery using the Danish version, no data in other languages or in patients undergoing TAVIare available. A validation in other languages is certainly required before it can be broadly recommended for patients with AS.

The Kansas City Cardiomyopathy Questionnaire (KCCQ) is a validated self-administered questionnaire that has a 2-week recall period and consists of 23 items targeting specific health domains, including physical limitation, symptoms, QoL, social limitation, and self-efficacy [19]. It is one of the most frequently used QoL tools in research on AS. Scores for the domains range from 0 to 100 and higher scores indicate lower symptom burden and better QoL. The clinical summary score combines measures of symptoms and social factors and the overall summary score integrates all the health domains.

Recently, a shorter 12-item version of the KCCQ, KCCQ-12, has been developed and validated [115]. It includes the symptom frequency, physical limitations, social limitations, and QoL domains. KCCQ-12 was highly correlated with the original KCCQ version and preserved the high test-retest reliability, responsiveness, prognostic ability, and interpretability, while reducing the response effort and time by half [115]. Choosing between KCCQ and KCCQ-12 depends on the intended use of the instrument. For example, the 23-item version should be used if symptom stability or self-efficacy outcomes are desired as these are not included in the shorter version of the questionnaire. The licenses for both KCCQ and KCCQ-12 have to be purchased at CvOutcomes.org.

The KCCQ has been widely tested for validity and reliability in different cardiac populations, including patients with AS, and has been shown to predict mortality and medical costs in such patients [106, 116, 117]. Arnold et al. examined 955 patients with severe symptomatic AS undergoing various treatment approaches and found that the KCCQ preserved its previously reported psychometric properties (validity, reliability, and responsiveness). Its scores were strongly associated with long-term mortality in patients who were medically treated for their AS [116].

The KCCQ was designed to address all health domains in a simple way that was comparably assessed in men and women and across a wide range of age groups and patients’ socioeconomic status. In addition, both short and long versions of the KCCQ have been translated into over 100 languages and can, therefore, be used in a large number of countries [115]. In comparison to other available QoL tools, the KCCQ is one of the most relevant instruments for application to patients with AS as there are many similarities between symptoms of AS to symptoms of heart failure.

A disadvantage of the KCCQ is the limited accuracy with which it can address changes in QoL following aortic valve replacement as questions are not symptom specific and cover other more general QoL variables, such as mobility. In addition, the questionnaire does not fully consider the psychological implications before and after undergoing a therapeutic intervention, although anxiety and depression have not extensively been researched so far in this patient population. Another potential disadvantage of the questionnaire is that its use is not free.

The Minnesota Living with Heart Failure Questionnaire (MLHF) is a validated, self-administered questionnaire used in the evaluation of QoL in chronic heart failure patients [20, 118]. It measures respondents’ perceptions of how heart failure affects physical, socioeconomic, and psychological aspects of their life. The questionnaire is divided into physical and emotional subscales with a total of 21 items. Answers are given on a scale of 0 (no influence) to 5 (strongest influence). The total score, ranging from 0 to 105, is obtained by summing the scores from individual questions with a lower score indicating better QoL. A total score of less than 24 represents good health, 24–45 moderate health, and 45–105 poor health. In addition, selected items also provide scores related to physical and emotional QoL parameters. A change in the score of 5 points or more is regarded as clinically significant [119]. MLHF can be purchased from the University of Minnesota’s website (https://license.umn.edu/product/minnesota-living-with-heart-failure-questionnaire-mlhfq).

Although designed for heart failure patients, the MLHF has been frequently implemented in QoL research with AS population [96, 64, 25, 65, 120]. Supino et al. [121] examined psychometric properties of the MLHF in patients undergoing heart valve surgery and demonstrated that this measure was highly acceptable and maintained good psychometric properties. Specifically, the results indicated that the MLHF was well accepted before, soon after, and late after the heart valve surgery, with more than 90% of patients reporting ease of completion [121]. Moreover, Sandau et al. [122] reported acceptable internal consistency and reliability of the MLHF in patients with AS demonstrating that its use in this population is acceptable. However, authors noted that the tool must be supplemented with other issues of concern for patients with AS as the use of the MLHF alone would not address common disease-specific concerns, such as angina or light-headedness [122].

MLHF is a practical disease-specific QoL tool with well-documented validity, reliability, and sensitivity that is being widely used in cardiovascular research. It is short and takes approximately 10 min to complete. Since its development, MLHF has been translated into at least 34 languages in various countries [102]. Similarly to the KCCQ, it may be appropriate to use the MLHF to assess QoL in patients with severe AS as most patients with AS also have heart failure and present with similar symptoms.

The clinical domains of MLHF were developed to measure specific QoL concerns of heart failure patients, which may not always be reflected in the AS patient population. In addition, the questionnaire does not cover some important domains of QoL impairment, such as impairment of social functioning or vitality. Lastly, the use of MLHF is not free.

The MacNew questionnaire is a self-administered QoL that was developed from revisions to the Quality of Life after Myocardial Infarction (QLMI) questionnaire [21, 22]. It was designed to assess patients’ feelings about how heart disease and its treatment impact their daily functioning in a 2-week timeframe. The questionnaire consists of 27 items with a global score and physical limitation, emotional function, and social function domains. The score in all domains ranges between 1 (poor QoL) and 7 (high QoL), and the global score is calculated as the mean of all scored items (unless one of the domains is completely missing).

The questionnaire has been proven to be a valid, reliable, and responsive instrument to assess QoL in patients with myocardial infarction, heart failure, ischemic heart disease, and angina [109]. Recently, Abdelaziz et al. [123] assessed QoL of 202 patients undergoing TAVI using the MacNew questionnaire and observed a significant improvement in all domains of QoL with improved discrimination of change in QoL compared with two other scales (EQ-5D and SF-36). The authors concluded that the MacNew questionnaire performed well in TAVI patients and could be used as an alternative disease-specific tool for assessing QoL change after TAVI [123]. The MacNew questionnaire can be downloaded at MacNew.org.

The MacNew questionnaire is easy to administer and has a straight-forward scoring interpretation. It is well-accepted by patients and can be applied to various diagnostic groups in the cardiovascular field. The questionnaire is currently available in over 45 languages and can be used in various countries. Also, the average completion time is less than 10 min.

Similarly to other heart failure-specific QoL measures, the MacNew questionnaire may not address important AS-related issues, including QoL changes following aortic valve replacement. Also, this questionnaire has only been used in 1 study with AS patients and needs further validation [123].

Toronto Aortic Stenosis Quality of Life Questionnaire (TASQ) is a recently validated QoL instrument, which, unlike other available measures, focuses specifically on the AS population [23]. It is the first questionnaire to address AS-specific symptoms and how they affect a patient’s physical and mental state. It also evaluates the patients’ assessment of their general health. The final version of the TASQ includes 16 questions addressing five health domains: physical symptoms, physical limitations, emotional impact, social limitations, and health expectations [23]. Each question has a maximum score of 7, giving the complete questionnaire a maximum total score of 112. Higher scores represent better perceived QoL.

Kennon et al. [26] found that the TASQ was a responsive measure of QoL in patients with severe AS and was sensitive to changes up to 3 months after aortic valve interventions. Questions and domains in the TASQ are relevant to the AS population as they were developed based on the subjective experiences and expectations reported in a large cohort of patients with AS [23]. The questionnaire is currently available in English, French, German, Italian, Spanish, Dutch, Chinese, Czech, Romanian, and Danish and can be accessed at Tasq-q.com [124]. A mobile application compatible with both Android and iOS operating systems can be downloaded in the respective app stores.

The TASQ is the only available QoL measurement tool developed specifically for patients with AS. It is a simple self-administered questionnaire with visually clear responses that provides valuable insight into the impact of AS and its treatment strategies in a patient’s daily life. It takes approximately 5 min to complete and is particularly suitable for older patients and busy clinical practices. The person-centered aspect of the TASQ highlights the substantial emotional and physical impact patients experience due to AS, as compared to other scales, and helps improve patient-clinician communication. Another advantage of the TASQ is that it incorporates a comprehensive approach to QoL as it addresses social and emotional domains, without a specific focus on physical cardiac symptoms, and serves as an effective basis for the decision regarding the AS treatment [23].

One limitation of TASQ is that it mainly consists of 7-point Likert scale questions, which could lead to inaccurate responses as participants may get inattentive and give the same scores for all questions. Additionally, due to its novelty, the psychometric properties of the TASQ have not been well documented in various populations and social demographics. Studies with large sample sizes utilizing TASQ are still needed to better evaluate the measurement properties of the questionnaire and confirm its usefulness in routine clinical care [23].

Patient QoL is increasingly being investigated as an outcome after the treatment of a chronic disease. This is particularly relevant for patients with severe AS, who often have a short life expectancy. In addition to post-operative clinical outcomes, such as hospitalizations and survival, QoL measures can help clinicians and researchers evaluate the AS treatment strategies and serve as a reference point for discussions between the patient and the clinician. In the long-term perspective, QoL indicators may influence the development of clinical pathways, service provision, healthcare expenditures, and public health policy. Most QoL tools vary in content and have their own specific application, and it may be challenging to find the right tool for the specific population. Due to the fact that most patients with severe AS also have heart failure, a large number of trials investigating QoL in patients with AS have used QoL instruments designed for the heart failure population, such as KCCQ and MLHF. However, the use of generic QoL tools is also common practice in AS research. Each instrument has its advantages and limitations and several practical and methodological considerations must be considered. Figure 2 shows a schematic representation of the reviewed QoL measures from the generic to AS-specific. The IIRS was excluded because it has not been fully tested in AS patients and was only used in one study as a comparison scale. As illustrated, the TASQ is the most specific QoL instrument for patients with AS covering all factors relevant to the QoL in this particular patient population. To the best of researchers’ knowledge, the current study is the first to review the characteristics of all the commonly used questionnaires for QoL assessment in patients with AS.

The two most commonly used generic QoL tools in the AS studies are SF-36/SF-12 and EQ-5D. The difference between them is that SF-36/SF-12 measures health status, which can be defined as a person’s perception of how their health affects their ability to perform functional tasks and daily activities, whereas EQ-5D measures health utility, which requires a person to assign a value to a particular state of health. The advantage of these generic instruments is that they can be used to effectively identify changes in different domains of patients’ health, allowing for comparisons across various conditions and interventions. However, due to their generic nature, such instruments do not measure the specific issues of AS and may, therefore, not be sensitive enough to detect small but clinically meaningful changes. Accordingly, disease-specific questionnaires have been developed in order to individually evaluate certain aspects of QoL and disease in a given population. Although several questionnaires specific for patients with HF have been both validated in studies with AS patients, TASQ holds a promising potential since it is the first AS-specific QoL tool. Currently, several ongoing studies are utilizing TASQ for measuring QoL in patients with AS [125, 126]. Another large upcoming registry in Romania is planning to use TASQ in patients with AS as well [127]. The implementation of TASQ in larger studies with AS patients will provide more information on its measurement properties, especially its responsiveness to change.

Based on the reviewed measures, there is a lack of consensus in measuring the impact of AS on QoL and a comprehensive QoL assessment that includes both disease-specific and generic QoL measures is currently recommended. Various questionnaires have specific dimensions, which may be of particular interest in some studies and should, therefore, be carefully reviewed in the study planning phase. The choice of a measure will also depend on several other issues, such as patient burden, health literacy, and clinical resources entailed in its use (cost and effort needed to administer, frequency of assessment, time required to enter results). If a clinician or researcher is interested in assessing a generic health perception of a patient with AS in various health domains, then SF-36/SF-12 is the most widely used. In patients with more advanced stages of the disease, measuring how much a person values their health using the EQ-5D questionnaire may be useful. EQ-5D can also be used if an economic and cost-utility analysis is planned. One of the domains of the KCCQ assesses the impact of heart failure symptoms that are common among patients with AS. Thus, this instrument may serve as a valid disease-specific measure in such patients when the impact of symptoms is of research interest. However, KCCQ does not address any psychological aspects of patients’ QoL, so MLHF or MacNew Questionnaire may be considered when emotional functioning is deemed to be important. Lastly, TASQ is the only AS-specific instrument that combines all health aspects measured in other currently used disease-specific questionnaires, focusing not only on physical symptoms or treatment issues but also on the social and emotional aspects of QoL. This novel instrument has, therefore, a potential for providing detailed information on the issues or effects that are specific to AS population. Since patients undergoing TAVI now include younger patients at low surgical risk with less severe symptoms its use should be increasingly considered when the research focuses on QoL in those patients.

Although many generic and disease-specific, particularly heart failure, QoL instruments have been implemented in the AS research, the ultimate goal should be the utilization of a single-core QoL measure in AS studies, which will allow within- and between-study comparisons of diagnosis and treatment using the same instrument. This will promote the development of a cumulative evidence based on QoL in AS. Without a standardized universal approach to the evaluation of QoL, incorrect assumptions may be made, negatively impacting the shared decision-making around appropriate treatment options and areas of QoL most affected by the disease.

The evaluation of the instruments presented in this review should be perceived as the opinion of a group of experts in AS research. There were no formal, quantitative comparisons of QoL outcomes across studies that can potentially be assessed in a systematic review. The major goal of this review was to provide an overview of available QoL measures and recommendations for the practitioners and researchers for implementing these measures in clinical trials. Lastly, PubMed was the only journal database used for the article search.

Incorporating measures of QoL together with clinical measures of AS facilitate the assessment and clinical decision-making processes with the aim of optimizing the effectiveness of aortic valve replacement therapies. However, there are currently no uniform, worldwide standards for measurement of QoL outcomes in patients with AS. Generic instruments are well established in research but may need to be used together with disease-specific measures for an effective assessment of QoL in AS patients. Disease-specific questionnaires have been developed but have not been used in many studies so far. We believe that there is a real need for AS-specific research into the QoL of patients as life prolongation may compete for an improved QoL in this elderly patient group.

Ethical approval was not required for this study.

Rima Styra has the copyright for the TASQ. Peter Bramlage is the representative of IPPMed, Cloppenburg, Germany. Jana Kurucova is an employee of the funder. Simon Kennon, Nikolaos Bonaros, Mauro Romano, Carlo Di Mario, Dirk-Jan van Ginkel, Wilbert Bor, Markus Kasel, Ole De Backer, Violetta Hachaturyan, and Claudia M. Lüske declare that they have no competing interests.

Research grant was provided by Edwards Lifesciences (Nyon, Switzerland) to the Sponsor Institute for Pharmacology and Preventive Medicine (IPPMed, Cloppenburg, Germany).

Derk Frank, Peter Bramlage, and Violetta Hachaturyan drafted the manuscript. Simon Kennon, Nikolaos Bonaros, Mauro Romano, Carlo Di Mario, Dirk-Jan van Ginkel, Wilbert Bor, Markus Kasel, Ole De Backer, Claudia M. Lüske, Jana Kurucova, and Rima Styra revised the article for important intellectual content, gave final approval of the version to be published, and are fully accountable for the content of the manuscript.