Heart Failure with Preserved Ejection Fraction (HFpEF) Pathophysiology Study (IDENTIFY-HF): Does Increased Arterial Stiffness Associate with HFpEF, in Addition to Ageing and Vascular Effects of Comorbidities? Rationale and Design

Overview

Journal BMJ Open

Specialty General Medicine

Date 2019 Nov 22

PMID 31748285

Citations 4

Authors

Danish Ali

Nualla Callan

Stuart Ennis

Richard Powell

Scott McGuire

Gordon McGregor

Martin O Weickert

Michelle A Miller

Francesco P Cappuccio

Prithwish Banerjee

Affiliations

Soon will be listed here.

Abstract

Aims: There has been a paradigm shift proposing that comorbidities are a major contributor towards the heart failure with preserved ejection fraction (HFpEF) syndrome. Furthermore, HFpEF patients have abnormal macrovascular and microvascular function, which may significantly contribute towards altered ventricular-vascular coupling in these patients. The IDENTIFY-HF study will investigate whether gradually increased arterial stiffness (in addition to ageing) as a result of increasing common comorbidities, such as hypertension and diabetes, is associated with HFpEF.

Methods And Analysis: In our observational study, arterial compliance and microvascular function will be assessed in five groups (Groups A to E) of age, sex and body mass index matched subjects (age ≥70 years in all groups):Group A; normal healthy volunteers without major comorbidities such as hypertension and diabetes mellitus (control). Group B; patients with hypertension without diabetes mellitus or heart failure (HF). Group C; patients with hypertension and diabetes mellitus without HF. Group D; patients with HFpEF. Group E; patients with heart failure and reduced ejection fraction (parallel group). Vascular function and arterial compliance will be assessed using pulse wave velocity, as the primary outcome measure. Further outcome measures include cutaneous laser Doppler flowmetry as a measure of endothelial function, transthoracic echocardiography and exercise tolerance measures. Biomarkers include NT-proBNP, high-sensitivity troponin T, as well as serum galectin-3 as a marker of fibrosis.

Ethics And Dissemination: The study was approved by the regional research ethics committee (REC), West Midland and Black Country 17/WM/0039, UK, and permission to conduct the study in the hospital was also obtained from the RDI, UHCW NHS Trust. The results will be published in peer-reviewed journals and presented in local, national and international medical society meetings.

Trial Registration Number: NCT03186833.

Citing Articles

The spectrum and systemic associations of microvascular dysfunction in the heart and other organs.

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PMID: 39196132 DOI: 10.1038/s44161-022-00045-5.

Rising arterial stiffness with accumulating comorbidities associates with heart failure with preserved ejection fraction.

Ali D, Tran P, Ennis S, Powell R, McGuire S, McGregor G ESC Heart Fail. 2023; 10(4):2487-2498.

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The Role of the Vasculature in Heart Failure.

Joshi M, Tran P, Barber T, Ayub W, Kuehl M, Banerjee P Curr Heart Fail Rep. 2023; 20(3):179-190.

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State-of-the-Art Review of Current Therapies for HFpEF: An Overview of Interatrial Septal Device Therapy in Heart Failure.

Al-Sadawi M, Ortega R, Ariyaratnam J, Battisha A, Madoukh B, Bukharovich I Curr Cardiol Rev. 2020; 17(5):e230421189012.

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References

Holland A, Spruit M, Troosters T, Puhan M, Pepin V, Saey D . An official European Respiratory Society/American Thoracic Society technical standard: field walking tests in chronic respiratory disease. Eur Respir J. 2014; 44(6):1428-46. DOI: 10.1183/09031936.00150314. View

Wang M, Tsai W, Chen J, Cheng M, Huang J . Arterial stiffness correlated with cardiac remodelling in patients with chronic kidney disease. Nephrology (Carlton). 2007; 12(6):591-7. DOI: 10.1111/j.1440-1797.2007.00826.x. View

Schiller N, Shah P, Crawford M, DeMaria A, Devereux R, FEIGENBAUM H . Recommendations for quantitation of the left ventricle by two-dimensional echocardiography. American Society of Echocardiography Committee on Standards, Subcommittee on Quantitation of Two-Dimensional Echocardiograms. J Am Soc Echocardiogr. 1989; 2(5):358-67. DOI: 10.1016/s0894-7317(89)80014-8. View

Balmain S, Padmanabhan N, Ferrell W, Morton J, McMurray J . Differences in arterial compliance, microvascular function and venous capacitance between patients with heart failure and either preserved or reduced left ventricular systolic function. Eur J Heart Fail. 2007; 9(9):865-71. DOI: 10.1016/j.ejheart.2007.06.003. View

Mayet J, Hughes A . Cardiac and vascular pathophysiology in hypertension. Heart. 2003; 89(9):1104-9. PMC: 1767863. DOI: 10.1136/heart.89.9.1104. View

Yancy C, Lopatin M, Stevenson L, De Marco T, Fonarow G . Clinical presentation, management, and in-hospital outcomes of patients admitted with acute decompensated heart failure with preserved systolic function: a report from the Acute Decompensated Heart Failure National Registry (ADHERE) Database. J Am Coll Cardiol. 2006; 47(1):76-84. DOI: 10.1016/j.jacc.2005.09.022. View

Shah S, Kitzman D, Borlaug B, van Heerebeek L, Zile M, Kass D . Phenotype-Specific Treatment of Heart Failure With Preserved Ejection Fraction: A Multiorgan Roadmap. Circulation. 2016; 134(1):73-90. PMC: 4930115. DOI: 10.1161/CIRCULATIONAHA.116.021884. View

Borbely A, van der Velden J, Papp Z, Bronzwaer J, Edes I, Stienen G . Cardiomyocyte stiffness in diastolic heart failure. Circulation. 2005; 111(6):774-81. DOI: 10.1161/01.CIR.0000155257.33485.6D. View

Balady G, Arena R, Sietsema K, Myers J, Coke L, Fletcher G . Clinician's Guide to cardiopulmonary exercise testing in adults: a scientific statement from the American Heart Association. Circulation. 2010; 122(2):191-225. DOI: 10.1161/CIR.0b013e3181e52e69. View

10.

Banerjee P . Heart failure: a story of damage, fatigue and injury?. Open Heart. 2017; 4(2):e000684. PMC: 5652497. DOI: 10.1136/openhrt-2017-000684. View

11.

Zakeri R, Cowie M . Heart failure with preserved ejection fraction: controversies, challenges and future directions. Heart. 2018; 104(5):377-384. DOI: 10.1136/heartjnl-2016-310790. View

12.

Cook C, Cole G, Asaria P, Jabbour R, Francis D . The annual global economic burden of heart failure. Int J Cardiol. 2014; 171(3):368-76. DOI: 10.1016/j.ijcard.2013.12.028. View

13.

Remes J, Miettinen H, Reunanen A, Pyorala K . Validity of clinical diagnosis of heart failure in primary health care. Eur Heart J. 1991; 12(3):315-21. DOI: 10.1093/oxfordjournals.eurheartj.a059896. View

14.

Chan M, Lam C . How do patients with heart failure with preserved ejection fraction die?. Eur J Heart Fail. 2013; 15(6):604-13. DOI: 10.1093/eurjhf/hft062. View

15.

Ather S, Chan W, Bozkurt B, Aguilar D, Ramasubbu K, Zachariah A . Impact of noncardiac comorbidities on morbidity and mortality in a predominantly male population with heart failure and preserved versus reduced ejection fraction. J Am Coll Cardiol. 2012; 59(11):998-1005. PMC: 4687406. DOI: 10.1016/j.jacc.2011.11.040. View

16.

Roustit M, Cracowski J . Non-invasive assessment of skin microvascular function in humans: an insight into methods. Microcirculation. 2011; 19(1):47-64. DOI: 10.1111/j.1549-8719.2011.00129.x. View

17.

Alghatrif M, Strait J, Morrell C, Canepa M, Wright J, Elango P . Longitudinal trajectories of arterial stiffness and the role of blood pressure: the Baltimore Longitudinal Study of Aging. Hypertension. 2013; 62(5):934-41. PMC: 3880832. DOI: 10.1161/HYPERTENSIONAHA.113.01445. View

18.

Stehouwer C, Henry R, Ferreira I . Arterial stiffness in diabetes and the metabolic syndrome: a pathway to cardiovascular disease. Diabetologia. 2008; 51(4):527-39. DOI: 10.1007/s00125-007-0918-3. View

19.

. ATS/ACCP Statement on cardiopulmonary exercise testing. Am J Respir Crit Care Med. 2003; 167(2):211-77. DOI: 10.1164/rccm.167.2.211. View

20.

Massie B, Carson P, McMurray J, Komajda M, McKelvie R, Zile M . Irbesartan in patients with heart failure and preserved ejection fraction. N Engl J Med. 2008; 359(23):2456-67. DOI: 10.1056/NEJMoa0805450. View