Cardiac Structure And Function-based Phenotyping Of Heart Failure With Preserved Ejection Fraction And Concomitant Atrial Fibrillation

Objective:Heart failure（HF）with preserved ejection fraction（HFp EF）is a heterogeneous clinical syndrome and accounts for over half of current HF.At least one-third of patients with HFp EF have concomitant AF.The outcomes of patients who have both AF and HF are considerably worse than those with either condition in isolation.The impact of AF on ventricular function and the interaction of the atrium with the ventricle,as well as the left with the right heart,are poorly understood.Cardiac structure and function-based phenotyping of HFp EF and concomitant AF（HFp EF-AF）is of pivotal importance for diagnosis,risk stratification,and even intervention.Our study aims to observe the clinical manifestations and changes in cardiac structure and function in HFp EF-AF and to explore its phenotypic characteristics.Methods:This was a cross-sectional study,and 835 consecutive newly-diagnosed HFp EF patients were assigned to the HFp EF-AF group（n=267）or the HFp EF alone group（n=568）according to whether they coexisted with AF.Comprehensive echocardiography and tissue Doppler techniques were employed to evaluate the cardiac structure and function.The HFA-PEFF score and the H₂FPEF score were retrospectively employed to confirm the diagnosis and assess the diagnostic consistency of the two score systems.One hundred and fifty-six cases of non-heart failure patients with cardiac risk factors matched in age and gender during the same period were selected as negative controls for ROC analysis,and 136 healthy people matched in age and gender were selected as healthy controls to determine the reference range of cardiac parameters.The cutoff points of the major cardiac parameters for the diagnosis of HFp EF-AF and HFp EF alone were derived from ROC analysis.We selected left atrial volume index（LAVi）,mitral annular systolic velocity（s’）and diastolic velocity（e’）,E/e’_L,E/e’_S,and right atrial area（RAA）as the analysis variables and conducted the systematic cluster analysis for the HFp EF-AF group,from which distinct clusters of HFp EF-AF were discovered,and the clinical and cardiac features of each cluster were analyzed and compared.Results:Compared with the HFp EF alone group,the left atrial volume index（LAVi）was larger,the left ventricular ejection fraction（EF）,mitral annular septal systolic velocity（s’_S）,and E/e’were less,the proportion of E/e’≤8 was higher,and the proportion of E/e’≥15 was lower in the HFp EF-AF group（all P<0.05）.Right ventricular diameter（RVD）,right atrial diameter（RAD）,RAA,tricuspid regurgitation velocity（TRv）,and pulmonary arterial systolic pressure（PASP）in the HFp EF-AF group were all greater than those in the HFp EF alone group（all P<0.05）.The abnormality rates of most right heart geometric parameters in HFp EF-AF were greater than those in HFp EF alone,of which the abnormality rate of RAA in HFp EF-AF doubled that in HFp EF alone.There was no difference in HFA-PEFF score between the two groups（P>0.05）.But the mean H₂FPEF score and the proportion of scores greater than 6 were markedly higher in the HFp EF-AF group than in the HFp EF alone group（P<0.01）;ROC curve analysis showed that E/e’had the highest diagnostic value in HFp EF alone with an AUC of 0.835,followed by RAA and LAVi with AUCs of 0.576and 0.569,respectively（both P<0.01）;in contrast,the diagnostic values of RAA and LAVi in HFp EF-AF were optimal with AUCs of 0.869 and 0.837,respectively（both P<0.01）;and E/e’had a moderate value,with AUC of 0.738（P<0.01）.With systematic cluster analysis of patients with HFp EF-AF two major clusters were obtained at a Euclidean distance of 60,with the number of cases in the two clusters being 118 and114,respectively.Subgroup analysis showed that,compared with Cluster 2,Cluster 1had a higher prevalence of hypertension,coronary heart disease,and diabetes mellitus,more severely decreased s’and e’,and more markedly elevated E/e’（all P<0.05）.And multiple linear regression showed that LAVi in cluster 1 was independently correlated with E/e’（r=0.313,P<0.05）,and RAA was independently correlated with PASP and RVD（all P<0.01）,being similar to those in the HFp EF alone group.In contrast,Cluster2 had a higher proportion of females,a longer duration of atrial fibrillation,more obvious enlargement of the right ventricle and right atrium,and more severe TRv and PASP,but right atrial and right ventricular size did not correlate with E/e’（all P>0.05）,nor did RAA correlate with PASP（P>0.05）,which were apparently different from those in the HFp EF alone and HFp EF-AF cluster 1.Conclusion:Overall,patients with HFp EF-AF had a further increase in LAVi,RAA,and RVD.The left ventricular dysfunction in HFp EF-AF shows a wide spectrum of diversity,from one phenotype with severer and another phenotype with milder damage than HFp EF alone.The HFA-PEFF score has high adaptability in both HFp EF alone and HFp EF-AF,but the H₂FPEF score may underestimate HFp EF alone in China.E/e’,LAVi,and RAA have different diagnostic values for HFp EF with or without AF,and RAA is not inferior to LAVi in the diagnosis of HFp EF-AF.Based on cardiac structure and function,two clusters of HFp EF-AF were derived,each with corresponding clinical features,implying two distinct phenotypes.The differences in the interaction of the atrium with the ventricle and the left with the right heart,suggesting different pathophysiology in the two phenotypes.