Left Atrial Stiffness Index Independently Predicts Exercise Intolerance and Quality of Life in Older, Obese Patients With Heart Failure With Preserved Ejection Fraction

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Abstract

Background

Heart failure with preserved ejection fraction (HFpEF) is the fastest growing form of HF and is associated with high morbidity and mortality. The primary chronic symptom in HFpEF is exercise intolerance, associated with reduced quality of life. Emerging evidence implicates left atrial (LA) dysfunction as an important pathophysiologic mechanism. Here we extend prior observations by relating LA dysfunction to peak oxygen uptake (peak VO2), physical function (distance walked in 6 minutes [6MWD]) and quality of life (Kansas City Cardiomyopathy Questionnaire).

Methods and Results

We compared 75 older, obese, patients with HFpEF with 53 healthy age-matched controls. LA strain was assessed by magnetic resonance cine imaging using feature tracking. LA function was defined according to its 3 distinct phases, with the LA serving as a reservoir during systole, as a conduit during early diastole, and as a booster pump at the end of diastole. The LA stiffness index was calculated as the ratio of early mitral inflow velocity-to-early annular tissue velocity (E/e’, by Doppler ultrasound examination) and LA reservoir strain. HFpEF had a decreased reservoir strain (16.4 ± 4.4% vs 18.2 ± 3.5%, P = .018), lower conduit strain (7.7 ± 3.3% vs 9.1 ± 3.4%, P = .028), and increased stiffness index (0.86 ± 0.39 vs 0.53 ± 0.18, P < .001), as well as decreased peak VO2, 6MWD, and lower quality of life. Increased LA stiffness was independently associated with impaired peak VO2 (β = 9.0 ± 1.6, P < .001), 6MWD (β = 117 ± 22, P = .003), and Kansas City Cardiomyopathy Questionnaire score (β = –23 ± 5, P = .001), even after adjusting for clinical covariates.

Conclusions

: LA stiffness is independently associated with impaired exercise tolerance and quality of life and may be an important therapeutic target in obese HFpEF.

Registration

NCT00959660

Section snippets

Study Population

The design and conduct of the Study of the effect of Caloric Restriction and Exercise Training in Patients with Heart Failure and a Normal Ejection Fraction (SECRET) has been described previously (NCT00959660).3 Briefly, inclusion criteria were: age 60 years or older, left ventricular (LV) ejection fraction of 50% or higher, obesity as defined by a BMI of 30 kg/m2 or greater, and signs and symptoms of HF as assessed by an HF clinical score of 3 or greater on the National Health and Nutrition

Patient Characteristics

Of the 100 participants with HFpEF included in the parent trial,3 19 did not undergo cardiac MRI owing to claustrophobia (n = 11), stent/pacemaker contraindication (n = 3), or scanner-related weight/circumference limitations (n = 5). Of the 81 MRIs that were completed, data from 6 participants were excluded owing to poor image or data quality. Compared with controls, study participants with HFpEF were predominantly female, less frequently of White race, and had higher weight and BMI (Table 1).

Discussion

The major novel finding of this investigation is that LA stiffness index is independently predictive of peak VO2, 6MWD, and quality of life. Together, the data suggest that impaired LA function, particularly increased LA stiffness, may be an important pathophysiologic contributor to exercise intolerance in HFpEF, representing a potential therapeutic target to improve quality of life.

LA structure and function are increasingly recognized as important pathophysiologic markers of disease severity.

Conclusions

Older, obese patients with HFpEF have impaired LA function with increased LA stiffness. These differences independently predict decreased peak VO2, functional capacity, and quality of life. Together, these data highlight the importance of assessing LA function and contribute to a growing body of evidence identifying LA stiffness as a potential therapeutic target in HFpEF.

Supplementary Table 1. Full Models of Predictors of Outcomes

Disclosures

Dr Kitzman reported receiving honoraria outside the present study as a consultant for Bayer, Merck, Medtronic, Relypsa, Merck, DCRI, Corvia Medical, Boehringer-Ingelheim, NovoNordisk, Astra Zeneca, and Novartis, and grant funding outside the present study from Novartis, Bayer, NovoNordisk, and Astra Zeneca, and stock ownership in Gilead Sciences.

Funding Support

Supported in part by the following research grants from the National Institutes of Health: R01AG045551; R01AG18915; P30AG021332; P30AG028716; P01HL137630. Also supported in part by the Kermit Glenn Phillips II Chair in Cardiovascular Medicine (DW Kitzman), the American Heart Association (TJ Samuel: 18PRE33960358), and the Potratz Family Endowment at the University of Texas at Arlington (MD Nelson).

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