Exercise-Induced Left Atrial Hypertension in Heart Failure With Preserved Ejection Fraction

Litwin, Sheldon E.; Komtebedde, Jan; Hu, Mo; Burkhoff, Daniel; Hasenfuß, Gerd; Borlaug, Barry A.; Solomon, Scott D.; Zile, Michael R.; Mohan, Rajeev; Khawash, Rami; Sverdlov, Aaron L.; Fail, Peter S.; Chung, Eugene S.; Kaye, D.; Blair, J. Anthony; Eicher, Jean‐Christophe; Hummel, Scott L.; Zirlik, Andreas; Westenfeld, Ralf; Hayward, Christopher; Gorter, Thomas M.; Demers, Catherine; Shetty, Ranjith; Lewis, Gregory D.; Starling, Randall C.; Patel, Sanjay; Gupta, Deepak K.; Morsli, Hakim; Pěnička, Martin; Čikeš, Maja; Gustafsson, Finn; Silvestry, Frank E.; Rowin, Ethan J.; Cutlip, Donald E.; Leon, Martin B.; Kitzman, Dalane W.; Kleber, Franz X.; Shah, Sanjiv J.

doi:10.1016/j.jchf.2023.01.030

Cited by 18 publications

(8 citation statements)

References 20 publications

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“…In the recently conducted REDUCE LAP-HF II trial, which investigated the utility of an inter-atrial shunt device on outcomes in patients with HFpEF, exercise-induced LA hypertension in the absence of resting LA hypertension was common in HFpEF. 14 We therefore believe that the association between LAVI and increased PVR at rest in the current study may be attributed to exercise-induced increases in LA pressure that have an impact on LA structure and function, and, ultimately, PA pressure, over time. Despite these limitations, the authors should be congratulated for completing a retrospective study that combines echocardiographic and haemodynamic data to further understand our knowledge of HFpEF phenotypes.…”

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confidence: 66%

The left atrium: a window into cardiopulmonary haemodynamics in heart failure with preserved ejection fraction

Peigh

Patel

2023

European J of Heart Fail

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This article refers to 'Left atrial enlargement is associated with pulmonary vascular disease in heart failure with preserved ejection fraction' by E.K. Gard et al., published in this issue on pages 806-814.Left atrial (LA) myopathy, defined as 'any complex of structural, architectural, contractile or electrophysiological changes affecting the atria with the potential to produce clinically-relevant manifestations' is present in certain individuals with heart failure with preserved ejection fraction (HFpEF). 1 Indeed, in patients with HFpEF, myocardial remodelling may occur in the left atrium independent of the left ventricle, and is associated with a unique proteomic signature reflective of extracellular matrix remodelling and immune dysregulation. 2,3 The pathophysiology of LA myopathy in HFpEF is complex, with mechanical, biochemical, and electrical mechanisms all contributing. Specifically, presence, compared to absence, of HFpEF is associated with higher degrees of LA fibrosis, abnormal ion channel expression, 4 impaired contractile function, 5 and increased markers of inflammation including tumour necrosis factor-α, NADPH oxidase, and interleukin-6. 6,7 In addition, patients with HFpEF have relatively high LA pressure that may be due to left ventricular (LV) diastolic dysfunction, intrinsic LA stiffness, or 'atrial' mitral regurgitation. 2 Increased LA pressure is subsequently associated with higher wall stress, further LA fibrosis, and increases in LA volume (LAV). 2 In this issue of the Journal, Gard and colleagues investigated the relationship between indexed LAV (LAVI) and invasive haemodynamics at rest and exertion in a selection of patients from the REDUCE LAP-HF trial and an internal cohort of patients with exertional dyspnoea. 8 The primary findings of the study are as follows: (i) higher LAVI was associated with blunted increase in cardiac output during exercise, higher mean pulmonary arterial (PA) pressure, and higher pulmonary vascular resistance (PVR); (ii) there was no association between LAVI and resting pulmonary capillary wedge * The opinions expressed in this article are not necessarily those of the Editors of the European Journal of Heart Failure or of the European Society of Cardiology.

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confidence: 66%

The left atrium: a window into cardiopulmonary haemodynamics in heart failure with preserved ejection fraction

Peigh

Patel

2023

European J of Heart Fail

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“…9 Moreover, patients with EILAH compared with those with elevated resting left atrial pressures are more likely to have atrial shunt responder characteristics. 10 In conclusion, invasive exercise hemodynamics with particular attention to pressure waveform morphology is simple and important for HFpEF diagnosis and phenotyping. Identifying HFpEF with primary atrial myopathy and EILAH may help direct therapeutic interventions.…”

Section: Discussionmentioning

confidence: 99%

Making Waves in HFpEF: Unmasking Severe Left Atrial Myopathy During Exercise

Dagan,

Kaye

2024

Circ: Heart Failure

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“…The primary strength of the MESA Early HF study is that it fills a gap in cardiovascular epidemiology studies by its inclusion of multi-dimensional HF phenotyping to evaluate the transition period from risk factors and abnormalities in cardiac structure/function (stages A and B HF) to clinically overt stage C HF with evidence of congestion at rest, which is easier to diagnose in the outpatient clinic or by hospitalizations for HF. This transition period, during which patients are symptomatic with breathlessness and reduced exercise tolerance, is difficult to diagnose, particularly in patients with HFpEF who at this stage are likely to have exercise-induced left atrial hypertension, 40 and likely missed in the clinical setting and yet may contribute to significant morbidity and may be amenable to novel therapies. Additional strengths include the parent MESA study, which is an ongoing, large-scale, population-based study involving 4 race/ethnic groups at 6 sites across the United States, and therefore is representative of the diverse US population.…”

Section: Discussionmentioning

confidence: 99%

Multi-Ethnic Study of Atherosclerosis Early Heart Failure Study: Rationale, Design, and Baseline Characteristics

Beussink-Nelson,

Freed,

Chirinos

et al. 2024

Circ: Heart Failure

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Background: Current prevalence estimates of heart failure (HF) are primarily based on self-report or HF hospitalizations. There is an unmet need to define the prevalence and pathogenesis of early symptomatic HF, which may be undiagnosed and precedes HF hospitalization. Methods: The MESA (Multi-Ethnic Study of Atherosclerosis) Early HF study was conducted during MESA exam 6 to determine the prevalence of early HF and investigate the transition from risk factors to early HF in a diverse population-based cohort of older adults. Between 2016 and 2018, 3285 MESA participants from 6 field centers underwent comprehensive speckle-tracking echocardiography with passive leg raise maneuver, Kansas City Cardiomyopathy Questionnaire, 6-minute walk test, arterial stiffness assessment, and proteomics (including NT-proBNP [N-terminal pro-B-type natriuretic peptide]). Results: Median age was 73 (25th–75th percentile 67–81) years, 53.2% were female, 25.6% were Black, 12.8% were Chinese, and 40.0% were White. The prevalence of HF risk factors was high: hypertension, 61.9%; former or current smoking, 53.7%; obesity 34.8%; diabetes; 24.7%; and chronic kidney disease; 22%. Overt cardiovascular disease, which ranged from 2.1% (HF) to 13.6% (atrial fibrillation), was less common. Of the 3285 participants, 96% underwent proteomics, 94% Kansas City Cardiomyopathy Questionnaire, 93% speckle-tracking echocardiography with passive leg raise, 82% arterial stiffness exam, and 77% 6-minute walk test. Feasibility of resting speckle-tracking echocardiography (87%–99% across cardiac chambers) and passive leg raise Doppler/speckle-tracking echocardiography (>84%) measurements was high. A total of 120 unique echocardiographic indices were measured. Conclusions: The MESA Early HF study is a key resource for cardiovascular researchers who are interested in improving the epidemiological and phenotypic characterization of early HF. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT00005487.

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Exercise-Induced Left Atrial Hypertension in Heart Failure With Preserved Ejection Fraction

Cited by 18 publications

References 20 publications

The left atrium: a window into cardiopulmonary haemodynamics in heart failure with preserved ejection fraction

The left atrium: a window into cardiopulmonary haemodynamics in heart failure with preserved ejection fraction

Making Waves in HFpEF: Unmasking Severe Left Atrial Myopathy During Exercise

Multi-Ethnic Study of Atherosclerosis Early Heart Failure Study: Rationale, Design, and Baseline Characteristics

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