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Non-invasive imaging, particularly echocardiography, plays a central role in the evaluation for heart failure with preserved ejection fraction (HFpEF). Echocardiography helps to rule in HFpEF among patients with unexplained dyspnea when the diagnosis is uncertain. In established HFpEF, echocardiography provides important insights into pathophysiology and phenotyping, such as isolated left ventricular diastolic dysfunction, left atrial dysfunction, abnormal right ventricular- pulmonary artery coupling, ischemia, or obesity phenotypes. Finally, imaging enables risk stratification for HFpEF. In this review, we will provide a critical appraisal of the role of echocardiography in the diagnosis and evaluation of HFpEF.

Five echocardiographic parameters-left atrial volume index, left ventricular mass index, tricuspid regurgitation velocity, myocardial tissue velocity, and the ratio of early mitral inflow to tissue velocity of the mitral annulus (E/e')-are recommended in both the current European Society of Cardiology heart failure guidelines and the American Society of Echocardiography/European Association of Cardiovascular Imaging recommendations for the evaluation of left ventricular diastolic function. We aimed to perform a systematic review of these echocardiographic parameters at resting conditions for their correlation with left ventricular filling pressures in patients with heart failure with preserved ejection fraction (HFpEF). In addition, the prognostic value of these parameters was assessed.Nine studies reported the correlation between echocardiography and invasive haemodynamics, and 18 papers reported on the prognostic value of echocardiography in HFpEF. Among the parameters, most data were reported for E/e'. The pooled correlation coefficient r was 0.56 for the relation between E/e' and invasively measured filling pressures. Combined weighted-mean meta-analysis of prognostic studies resulted in a hazard ratio of 1.05 (95% confidence interval 1.03-1.06) per unit increase in E/e' for the combined outcome of all-cause mortality and cardiovascular hospitalization. The other echocardiographic parameters, when taken individually, had similar or lower association with prognosis.Only a small number of studies validated the use of echocardiographic parameters at rest in patients with HFpEF. The best established parameter appears to be E/e', but the existing data only show modest correlations of E/e' with invasive filling pressures and outcomes in HFpEF.

Background A substantial proportion of patients with heart failure (HF) with preserved ejection fraction (HFpEF) present with normal natriuretic peptide (NP) levels. The pathophysiology and natural history for this phenotype remain unclear. Methods and results Consecutive subjects undergoing invasive cardiopulmonary exercise testing for unexplained dyspnoea at Mayo Clinic in 2006-18 were studied. Heart failure with preserved ejection fraction was defined as a pulmonary arterial wedge pressure (PAWP) >= 15 mmHg (rest) or >= 25 mmHg (exercise). Patients with HFpEF and normal NP [N-terminal of the pro-hormone B-type natriuretic peptide (NT-proBNP) < 125 ng/L] were compared with HFpEF with high NP (NT-proBNP >= 125 ng/L) and controls with normal haemodynamics. Patients with HFpEF and normal (n = 157) vs. high NP (n = 263) were younger, yet older than controls (n = 161), with an intermediate comorbidity profile. Normal NP HFpEF was associated with more left ventricular hypertrophy and worse diastolic function compared with controls, but better diastolic function, lower left atrial volumes, superior right ventricular function, and less mitral/tricuspid regurgitation compared with high NP HFpEF. Cardiac output (CO) reserve with exercise was preserved in normal NP HFpEF [101% predicted, interquartile range (IQR): 75-124%], but this was achieved only at the cost of higher left ventricular transmural pressure (LVTMP) (14 +/- 6 mmHg vs. 7 +/- 4 mmHg in controls, P < 0.001). In contrast, CO reserve was decreased in high NP HFpEF (85% predicted, IQR: 59-109%), with lower LVTMP (10 +/- 8 mmHg) compared with normal NP HFpEF (P < 0.001), despite similar PAWP. Patients with high NP HFpEF displayed the highest event rates, but normal NP HFpEF still had 2.7-fold higher risk for mortality or HF readmissions compared with controls (hazard ratio: 2.74, 95% confidence interval: 1.02-7.32) after adjusting for age, sex, and body mass index. Conclusion Patients with HFpEF and normal NP display mild diastolic dysfunction and preserved CO reserve during exercise, despite marked elevation in filling pressures. While clinical outcomes are not as poor compared with patients with high NP, patients with normal NP HFpEF exhibit increased risk of death or HF readmissions compared with patients without HF, emphasizing the importance of this phenotype. Key question What is the prognosis of patients with heart failure and preserved ejection fraction (HFpEF) who have normal natriuretic peptide (NP) levels? How does this group present in terms of cardiac structure and function, and haemodynamics at rest and during exercise? Key finding Patients with HFpEF and normal NP levels have increased mortality and heart failure readmissions compared with subjects with non-cardiac dyspnoea. Heart failure and preserved ejection fraction with elevated vs. normal NP levels is associated with worse right ventricular function, more secondary valve regurgitation, and impaired cardiac output reserve. Take-home message A considerable number of patients with HFpEF present with normal NP levels. Those patients exhibit increased morbidity and mortality in comparison with patients without heart failure, emphasizing the importance of this phenotype. F.H.V. is supported by a Fellowship of the Belgian American Educational Foundation (B.A.E.F.) and by the Special Research Fund (BOF) of Hasselt University (BOF19PD04). B.A.B. is supported by R01 HL128526 from the National Institutes of Health. The authors thank the staff of the Earl Wood Catheterization Laboratory and the patients who agreed to participate in research, allowing for this study to be completed.