Letter by Zakeri and Redfield Regarding Article, "Influence of Left Atrial Function on Exercise Capacity and Left Ventricular Function in Patients With Heart Failure and Preserved Ejection Fraction".

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HomeCirculation: Cardiovascular ImagingVol. 10, No. 8Letter by Zakeri and Redfield Regarding Article, “Influence of Left Atrial Function on Exercise Capacity and Left Ventricular Function in Patients With Heart Failure and Preserved Ejection Fraction” Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessLetterPDF/EPUBLetter by Zakeri and Redfield Regarding Article, “Influence of Left Atrial Function on Exercise Capacity and Left Ventricular Function in Patients With Heart Failure and Preserved Ejection Fraction” Rosita Zakeri, MBChB, , PhD and Margaret M. Redfield, MD Rosita ZakeriRosita Zakeri Mayo Clinic, Rochester, MN Search for more papers by this author and Margaret M. RedfieldMargaret M. Redfield Mayo Clinic, Rochester, MN Search for more papers by this author Originally published8 Aug 2017https://doi.org/10.1161/CIRCIMAGING.117.006705Circulation: Cardiovascular Imaging. 2017;10:e006705To the Editor:We read with great interest the study by von Roeder et al1 which highlighted a pivotal role for left atrial (LA) functional remodeling in human heart failure with preserved ejection fraction (HFpEF).1 The authors report impaired LA conduit strain occurring at an early stage of HFpEF, where 1/3rd of patients had a normal brain type natriuretic peptide, and left ventricular (LV) concentric remodeling was apparently absent (equivalent end-diastolic volume and LV mass index between HFpEF and controls).We recently provided corroborative data in an early-stage large animal model of hypertensive HFpEF, using invasive LA pressure–volume relationships, also calibrated to cardiovascular magnetic resonance imaging-derived LA volumes.2 As in the present study, isolated LA volumetric analysis was not informative. However, directly assessed LA compliance was impaired (ie, an upwards and leftward shift in the LA end-reservoir pressure–volume relationship) and correlated with LV stroke volume at rest, at equivalent heart rate, providing a plausible mechanism for the observed relationship between LA conduit strain and peak VO2 in the present study. The authors do not provide these data. We wondered whether a correlation was observed between cardiovascular magnetic resonance imaging-derived LA conduit strain and LV stroke volume or cardiac output?Efficient mechanical matching between the LA and LV (systolic and physiological atrioventricular coupling) may also play a role in determining LV performance, as demonstrated by ourselves2 and others,3 which is conceivably heightened during stress, and worthy of assessment in human HFpEF studies.Von Roeder et al1 importantly advance the concept of an early intrinsic atrial myopathy in HFpEF, raising the question of potential therapeutic targets. We provided LA tissue analyses, suggesting that LA fibrosis may be a late finding, as for other experimental models of LV pressure-overload,4 and contrary to stipulations in the accompanying editorial. Nevertheless, early changes in titin phosphorylation status (hyperphosphorylation of LA titin) and reduced LA microvascular density were present and correlated with reduced LA compliance and may, therefore, represent suitable therapeutic targets. Similar processes are thought to underlie LV remodeling in HFpEF, supporting a paradigm of global myocardial remodeling in HFpEF that may be responsive to a disease-modifying therapy.5Finally, we congratulate the authors on their elegant study. We support the need for further analysis of LA pathophysiology and its therapeutic and prognostic importance in HFpEF.Rosita Zakeri, MBChB, PhDMargaret M. Redfield, MDMayo ClinicRochester, MNDisclosuresNone.