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Clinical course and outcomes in adults with co-occurring hypertrophic cardiomyopathy and hypertension: a scoping review protocol
  1. Milla Arabadjian1,
  2. Barnaby Nicolas2,
  3. Sophie Montgomery3,
  4. Mitchell Pleasure3,
  5. Maxine Collins4,
  6. Maria Reuter5,
  7. Daniele Massera5,
  8. Daichi Shimbo6,
  9. Mark Sherrid5
  1. 1Center for Population and Health Services Research, Department of Foundations of Medicine, NYU Long Island School of Medicine, Mineola, New York, USA
  2. 2Department of Foundations of Medicine, NYU Long Island School of Medicine, Mineola, New York, USA
  3. 3NYU Grossman School of Medicine, New York City, New York, USA
  4. 4University of Connecticut School of Nursing, Storrs, Connecticut, USA
  5. 5Hypertrophic Cardiomyopathy Program, Leon H. Charney Division of Cardiology, Department of Medicine, NYU Langone Health, New York City, New York, USA
  6. 6Division of Cardiology, Department of Medicine, Columbia University Irving Medical Center, New York City, New York, USA
  1. Correspondence to Dr Milla Arabadjian; milla.arabadjian{at}nyulangone.org

Abstract

Introduction Hypertension affects 40%–60% of adults with hypertrophic cardiomyopathy (HCM), the most common inherited cardiac condition. It can be a diagnostic confounder for HCM, contributing to delayed diagnosis. Clinically, treatment of co-occurring hypertension and HCM poses challenges as first-line and second-line antihypertensive medications are often contraindicated in HCM. The clinical course in adults with hypertension and HCM is also not well understood, and studies examining patient outcomes in this population are equivocal. In this paper, we aim to outline the protocol of a scoping review, a type of literature review, to systematically synthesise existing knowledge on adults with co-occurring HCM and hypertension, highlighting knowledge and evidence gaps, and identifying future research directions to optimise outcomes in this population.

Methods and analysis This review is guided by Arksey and O’Malley’s conceptual framework on conducting scoping reviews. We will search five electronic databases (PubMed, CINAHL, Scopus, Embase and Web of Science) and reference lists of publications to identify eligible articles focusing on medical therapy, clinical course or outcomes in adults with HCM and hypertension, between 2011 and 2023. Our search strategy and presentation of results will be guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses-Scoping Review guideline. First, two independent reviewers will screen articles, by title and abstract, followed by a full-text screen to identify eligible articles. Relevant data will be extracted and synthesised.

Ethics and dissemination Ethical approval is not required for this review as it is a secondary data collection of published articles and does not involve human subject participation. We will present results of this review at relevant professional conferences and patient-centred educational events. Results will be published in a peer-reviewed journal.

  • hypertension
  • hypertrophic cardiomyopathy
  • cardiology
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STRENGTHS AND LIMITATIONS OF THIS STUDY

  • With this scoping review, we will synthesise the literature on the clinical course and outcomes of adults with co-occurring hypertrophic cardiomyopathy and hypertension and will highlight knowledge gaps to inform future research directions.

  • We follow Preferred Reporting Items for Systematic Reviews and Meta-Analyses-Scoping Review guidelines to ensure methodological rigour in identifying eligible publications, and publication of the protocol will ensure methodological transparency.

  • Each stage of the review process will be completed by two independent study members.

  • The search strategy includes identifying eligible peer-reviewed articles from five electronic databases: PubMed, CINAHL, Scopus, Embase and Web of Science.

  • An inherent limitation of scoping reviews, including this one, is that the quality of the included articles will not be appraised.

Introduction

Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiac disorder with a prevalence of up to 0.5%.1 With advances in diagnosis and management, HCM is increasingly viewed as a manageable chronic condition.2 3 As such, there is a growing need to better understand and manage common comorbidities that impact individuals with HCM. Hypertension is the most common chronic condition in the USA, affecting 47.3% of the population overall, with noted racial disparities in prevalence and outcomes.4 5 It is a major risk factor for coronary artery disease, renal disease and stroke, and is associated with an increased risk of mortality.6 Hypertension co-occurs in approximately 40%–60% of adults with HCM, more commonly among women and black adults.7–10 Hypertension can be a diagnostic confounder for HCM as it contributes independently to left ventricular hypertrophy, a diagnostic hallmark of HCM.3 11 Patients often experience prolonged paths to an HCM diagnosis navigating multiple layers of the healthcare system, including seeing a variety of providers and being misdiagnosed with other conditions, before reaching an HCM specialist.12 Emerging cardiac magnetic resonance imaging techniques are increasingly used to differentiate between HCM and hypertension, but such imaging may not be widely available in community settings.13 14 Furthermore, co-occurrence of HCM and hypertension presents a clinical and management challenge as first-line and second-line antihypertensive agents are generally contraindicated in adults with obstructive HCM because they may worsen obstruction and exacerbate symptoms, like dyspnoea on exertion and exercise intolerance.3 6 Adults with obstructive HCM comprise the majority of HCM cases, approximately 70%.15 While first-line and second-line antihypertensive medications are not contraindicated in adults with non-obstructive HCM, confirming that patients are indeed not obstructed is important, as latent obstruction is sometimes challenging to diagnose and requires a thorough work-up, including provocative non-invasive and invasive manoeuvres, like echocardiographic imaging after eating, or after amyl nitrite administration.16 17 Data on the disease course, treatment and clinical outcomes in patients with both hypertension and HCM is limited, a knowledge gap that constrains clinical decision making and limits optimisation of outcomes.18–20

To optimise clinical care and ultimately clinical outcomes in those with both conditions, there is a need for systematic examination and synthesis of the evidence in the clinical course, management and outcomes in co-occurring HCM and hypertension. A preliminary search of the literature yielded limited results, thus we determined that a scoping review is the appropriate methodology for examining this topic. Scoping reviews are appropriate when there is limited literature on a topic, the review synthesises, but does not appraise the existing literature. A purpose of a scoping review is to also identify knowledge and evidence gaps on a topic.21 22

Study objectives

There are two overarching objectives of this scoping review: (1) to systematically scope the existing literature on the clinical course, management and outcomes in patients with co-occurring HCM and hypertension; (2) to describe knowledge and evidence gaps that will inform future targeted research directions to optimise clinical care and management of HCM and hypertension, and improve disease course and outcomes.

Methods and analysis

Conceptual model

This protocol is guided by the scoping review framework developed by Arksey and O’Malley,23 and advanced by Levac,21 which includes six stages: (1) identifying the research question; (2) identifying relevant studies; (3) study selection; (4) charting the data; (5) collating, summarising and reporting the results (data summary and synthesis); and (6) consultation. The scoping review protocol has been preregistered with the Open Science Framework (https://osf.io/cy8qb/?view_only=98197f4850584e51807ff9b62533a706).

Identifying the research question

This scoping aims to systematically examine and synthesise the existing literature on the clinical course and outcomes in patients with co-occurring HCM and hypertension. Specifically, our questions include:

  1. How is hypertension defined in existing publications focused on HCM and hypertension (eg, self-report, medical history, blood pressure measurement, etc)?

  2. What medical regimens are used to treat adults with co-occurring HCM and hypertension?

  3. What is the clinical disease burden in adults with co-occurring HCM and hypertension, versus those with HCM alone, including quality of life, symptoms and functional limitations (NYHA class, exercise tolerance)?

  4. What are the clinical outcomes in adults with co-occurring HCM and hypertension, versus those with HCM alone? These include hypertension-related outcomes including renal dysfunction, ischaemic stroke and coronary artery disease; HCM-related outcomes including arrhythmia, sudden death, appropriate implantable cardioverter defibrillator shocks and invasive interventions (myectomy, alcohol septal ablation); and all-cause mortality.

Identifying relevant studies

The search strategy will aim to locate published peer-reviewed studies. An initial limited search of PubMed was undertaken to identify articles on the topic. The text words contained in the titles and abstracts of relevant articles, and the index terms used to describe the articles were used to develop a full search strategy for PubMed, CINAHL, Scopus, Embase and Web of Science. The search strategy, including all identified keywords and index terms, will be adapted for each included database and/or information source. The reference list of all included sources of evidence will be screened for additional studies.

A comprehensive literature search will be performed to locate published studies in the following research databases: PubMed (MEDLINE), Web of Science (Clarivate), CINAHL (EBSCO), Scopus (Elsevier) and Embase (via OVID). A preliminary search in the Cochrane Database of Systematic Reviews did not reveal any systematic or scoping reviews related to co-occurring HCM and hypertension. Beyond databases, we will examine reference lists from eligible articles and will add additional publications for review. Eligibility criteria for the studies are listed in table 1. In order to maximise yield, we will include all eligible publications from November 2011 until February 2023. The starting date was chosen as the first clinical guidelines on the management and care of patients with HCM was published then.24 All references will be collected from each database and stored using EndNote 20 (Philadelphia, Pennsylvania, USA), a reference management software, to then be imported into Covidence,25 an evidence synthesis management software. After successful import, duplicate references will be removed. Search terms are presented in table 2.

Table 1

Eligibility criteria

Table 2

Search terms per database (performed on 15 February 2023)

Study selection

Once imported into Covidence, the evidence synthesis management software, duplicates will be removed. The process of identifying relevant articles will follow a three-step process. First, article titles and abstracts will be screened for studies fitting the eligibility criteria. Two independent reviewers (SM and MP) will screen titles and abstracts, to reduce bias (ref). If there is a disagreement on inclusion, a third reviewer (MA) will assist in the selection of relevant articles. The reviewers will meet at the beginning of the abstract review process to clarify eligibility criteria and discuss relevant search terms, and at the midpoint, and final stages of the abstract review process to discuss and address any challenges or uncertainties related to study selection.

The second stage will include full-text review to examine and confirm eligibility criteria and will follow the same process, with two independent reviewers making determinations, with a third reviewer assisting and resolving disagreements. Third, once relevant publications have been included, reviewers (MR, SM, MP and MA) will examine reference lists and will identify potential additional studies that may fit the inclusion criteria for the review. Reasons for exclusion of articles will be noted. We will report the flow of information through the different phases of the scoping review following the 26Preferred Reporting Items for Systematic Reviews and Meta-Analyses-Scoping Review guidelines (figure 1).

Figure 1

Preferred Reporting Items for Systematic Reviews and Meta-Analyses-Scoping Review flow chart.

Charting the data

Predetermined data extraction forms will be developed and reviewed by the research team (coauthors). Forms will capture general information including first author, publication date and study type. Study-related extracted data will include sociodemographic and clinical characteristics of participants, quality of life measures, symptoms and functional class. We will capture outcome data. We will extract hypertension related data, including hypertension characterisation (definition) among study cohort, use of hypertension variable as exposure versus covariate (table 3). Data will be extracted by two independent reviewers. The review team will meet after data have been extracted from 25% of the articles, in order to determine whether the data extraction approach is consistent with the research questions and the overall review purpose.

Table 3

Data extraction template

Data summary and synthesis of results

Scoping reviews aim to examine the ‘state of the science’ when there are limited and heterogeneous approaches to an emerging topic. A strength of scoping reviews is the ability to identify knowledge and evidence gaps and identify future research directions, in effect acting as a ‘call to action’. However, one limitation of scoping reviews is that quality appraisal is not a typical feature of this review modality, thus lower quality evidence may be included. However, we have minimised this limitation with our rigorous eligibility criteria.

We will present extracted (synthesised) data in a systematic manner, first reporting general study cohort characteristics, then sequentially to address our specific research questions. We will then discuss clinical implications of findings, we will describe gaps in the literature, and we will identify future research targets to optimise clinical management, care and outcomes in adults with co-occurring HCM.

Consultation

The research team comprises clinical and research HCM and hypertension experts who will assist in framing the results of this scoping review into context and will provide input onto discussing relevant knowledge and evidence gaps, and help identify targeted directions for clinical and research investigations.

Patient and public involvement

There is no patient or public involvement in the development in this scoping review protocol.

Ethics and dissemination

Ethical approval is not required for this review as it is a secondary data collection of published articles and does not involve human subject participation. Findings will be disseminated via conference presentations, patient-centred educational events and peer-reviewed publications. This scoping review will improve understanding of a challenging clinical problem.

Ethics statements

Patient consent for publication

References

Footnotes

  • Contributors MA was involved with project conceptualisation, data analysis, writing of the original draft and subsequent editing, and is the corresponding author; BN was involved with conceptualising and performing to scoping review search strategy, editing of manuscript; SM, MP, MC and MR were involved with data collection, data analysis and manuscript editing; DM was involved with data analysis and manuscript editing; DS and MS were involved with review design and manuscript editing.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests MA reports advisory board fees from Bristol-Meyers Squibb; DM reports advisory board/consulting fees from Bristol-Meyers Squibb, advisory board/consulting/speaker fees from Sanofi and advisory board/consulting fees from Tenaya Therapeutics; MR reports advisory board fees from Bristol-Meyers Squibb; MS reports consulting fees from Pfizer, Inc. The rest of the authors report no financial disclosures.

  • Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.

  • Provenance and peer review Not commissioned; externally peer reviewed.