Disproportionate left atrial myopathy in heart failure with preserved ejection fraction among participants of the PROMIS-HFpEF study

Abstract

Impaired left atrial (LA) function in heart failure with preserved ejection fraction (HFpEF) is associated with adverse outcomes. A subgroup of HFpEF may have LA myopathy out of proportion to left ventricular (LV) dysfunction; therefore, we sought to characterize HFpEF patients with disproportionate LA myopathy. In the prospective, multicenter, Prevalence of Microvascular Dysfunction in HFpEF study, we defined disproportionate LA myopathy based on degree of LA reservoir strain abnormality in relation to LV myopathy (LV global longitudinal strain [GLS]) by calculating the residuals from a linear regression of LA reservoir strain and LV GLS. We evaluated associations of disproportionate LA myopathy with hemodynamics and performed a plasma proteomic analysis to identify proteins associated with disproportionate LA myopathy; proteins were validated in an independent sample. Disproportionate LA myopathy correlated with better LV diastolic function but was associated with lower stroke volume reserve after passive leg raise independent of atrial fibrillation (AF). Additionally, disproportionate LA myopathy was associated with higher pulmonary artery systolic pressure, higher pulmonary vascular resistance, and lower coronary flow reserve. Of 248 proteins, we identified and validated 5 proteins (involved in cardiomyocyte stretch, extracellular matrix remodeling, and inflammation) that were associated with disproportionate LA myopathy independent of AF. In HFpEF, LA myopathy may exist out of proportion to LV myopathy. Disproportionate LA myopathy is a distinct HFpEF subtype associated with worse hemodynamics and a distinct proteomic signature, independent of AF.

Impact of different degrees of left ventricular strain on left atrial mechanics in heart failure with preserved ejection fraction

“…These findings support the interrelated nature of the mechanical processes of both chambers. However, disproportionate LA malfunction from intrinsic LA abnormalities in some of HFpEF patients may be another factor that explains why the correlation of LAS r and GLS is only moderate [ 29 ].…”

The future of heart failure with preserved ejection fraction

“…Recently, they defined a unique LA myopathy phenotype in HFpEF in the PROMIS-HFpEF observational study by taking the residuals of linear regression of LA reservoir strain and LV longitudinal strain to define a continuous phenotype that ranges from LA-preserved, to LA/LV-balanced, to LA-predominant (LA myopathy) phenotypes (Fig. 1 a; [ 44 ]). The LA myopathy phenotype is associated with better LV systolic and diastolic function but worse hemodynamics (lower stroke volume, increased pulmonary artery pressure).…”

Left Atrial Cardiomyopathy – A Challenging Diagnosis

“…Moreover, there is an association with AF burden (114). An inverse relationship was reported between higher levels of endothelin-1, N-terminal pro-B-type natriuretic peptide, troponin I and lower LA reservoir and contractile strain, suggesting that LA myopathy is associated with persistent congestion (126,127). Oldgren et al evaluated the ABC-stroke score, derived from the ARISTOTLE study, including age, biomarkers (N-terminal pro-B-type natriuretic peptide and highsensitivity cardiac troponin), and clinical history (prior stroke) (128,129).…”

“…Several risk factors for the development of AF as well as structural and electrical remodeling in terms of a possible LACM have been described. LACM may occur as a result of amyloidosis, hereditary muscular dystrophies, congestive heart failure, AF, obstructive sleep apnea, drugs, alcohol, myocarditis, genetic repolarization disturbances, aging, hypertension, obesity, diabetes mellitus, valvular heart disease ( 9 , 127 , 141 – 143 ) ( Figure 7 ).…”