Diagnosis of Heart Failure With Preserved Ejection Fraction Relies on Detection of Increased Diastolic Filling Pressure, But How?

Abstract

HomeJournal of the American Heart AssociationVol. 12, No. 6Diagnosis of Heart Failure With Preserved Ejection Fraction Relies on Detection of Increased Diastolic Filling Pressure, But How? Open AccessEditorialPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citations ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toOpen AccessEditorialPDF/EPUBDiagnosis of Heart Failure With Preserved Ejection Fraction Relies on Detection of Increased Diastolic Filling Pressure, But How? Jae K. Oh, MD, William R. Miranda, MD and Garvan C. Kane, MD, PhD Jae K. OhJae K. Oh *Correspondence to: Jae K. Oh, MD, Department of Cardiovascular Medicine Mayo Clinic 200 1st Street SW, Rochester, MN 55905. Email: E-mail Address: [email protected] https://orcid.org/0000-0002-8303-5780 , Department of Cardiovascular Medicine, , Mayo Clinic, , Rochester, , MN, Search for more papers by this author , William R. MirandaWilliam R. Miranda https://orcid.org/0000-0001-8864-8474 , Department of Cardiovascular Medicine, , Mayo Clinic, , Rochester, , MN, Search for more papers by this author and Garvan C. KaneGarvan C. Kane , Department of Cardiovascular Medicine, , Mayo Clinic, , Rochester, , MN, Search for more papers by this author Originally published9 Mar 2023https://doi.org/10.1161/JAHA.122.028867Journal of the American Heart Association. 2023;12:e028867This article is a commentary on the followingDiscriminative Role of Invasive Left Heart Catheterization in Patients Suspected of Heart Failure With Preserved Ejection FractionOther version(s) of this articleYou are viewing the most recent version of this article. Previous versions: March 9, 2023: Ahead of Print In this issue of the Journal of the American Heart Association (JAHA), Ki Hong Choi et al publish an important study in a Korean population to show the diagnostic and prognostic value of left ventricular end‐diastolic pressure (LVEDP) in patients with suspected heart failure with preserved ejection fraction (HFpEF).1 Of 404 patients with suspected HFpEF, LVEDP was ≥16 mm Hg in 80%, consistent with HFpEF, and this group of patients was found to have higher heart failure assoication‐pretest assessment, echocardiography, functional testing, and final etiology (HFA‐PEFF) scores than the 20% of patients with noncardiac dyspnea who had LVEDP <16 mm Hg. Although the HFA‐PEFF score was associated with a significantly higher 10‐year risk of death‐ or heart failure‐related events, the score was in the intermediate range for a significant proportion (56%) of the study patients. Even in this group, increased LVEDP was associated with a significantly higher risk than in patients with LVEDP <16 mm Hg. Therefore, the authors correctly concluded that invasively measured LVEDP can provide additional discriminative value to diagnose HFpEF or to predict a worse outcome, especially in patients with intermediate HFA‐PEFF scores.Clinical Scores for the Diagnosis of HFpEF:HFA‐PEFF and Heavy, Hypertensive, Atrial Fibrillation, Pulmonary Hypertension, Elder, Filling Pressure (H2FPEF)The HFA‐PEFF diagnostic algorithm published in 2019 incorporates functional, morphological, and biomarker parameters into creating a scoring system to classify suspected patients as having low, intermediate, and high probability for HFpEF.2 This same guideline recommends exercise hemodynamics, either by diastolic stress echocardiography or invasively, when the score is in the intermediate range, as often occurs in clinical practice, LVEDP ≥16 mm Hg or pulmonary artery wedge pressure (PAWP) ≥15 mm Hg at rest and PAWP ≥25 mm Hg with exercise were recommended to define HFpEF. Another diagnostic algorithm, H2FPEF score, was introduced in 2018 by Reddy et al relying on clinical characteristics (obesity, hypertension, and atrial fibrillation) and echocardiography (tricuspid regurgitation velocity and E/e′) variables.3 In this proposal, the same PAWP values at rest and with exercise used in HFA‐PEFF defined HFpEF, but the LVEDP definition was not used. Noteworthy, these scores incorporate absolute PAWP or LVEDP values during exercise for the diagnosis of HFpEF. Alternatively, the use of increases in PAWP indexed to change in flow (delta PAWP/delta cardiac output slope) has been suggested to be more sensitive for diagnosis of HFpEF.4 This parameter would be reflective of the compliance of left‐sided chambers and, for example, would allow for diagnosis of HFpEF in those with less impressive elevations in filling pressures and/or those unable to significantly increase cardiac output during exercise. A PAWP/delta cardiac output slope >2 has also been described to be predictive of incident heart failure in patients with exertional dyspnea.4LVEDP and PAWP as Invasive Measures of Left Ventricular Filling PressuresThe latest diastolic function guideline document by the American Society of Echocardiography and the European Association of Cardiovascular Imaging defines invasive hemodynamics of PAWP >12 mm Hg or LVEDP >16 mm Hg at rest as elevated filling pressure but cautions that mean diastolic pressure can be normal when an increase in LVEDP is used as the only evidence of diastolic dysfunction.5 Although some studies have used LVEDP and PAWP interchangeably, it is critical to understand that those 2 pressures reflect different hemodynamic phenomena. The pitfalls in interpreting and comparing these measurements in health and disease were highlighted by Rahimtoola almost 50 years ago.6 LVEDP corresponds to the instantaneous pressure in the left ventricle immediately before isovolumic contraction. Therefore, it is a metric of left ventricular (LV) compliance, reflecting the rise in LV diastolic pressure following atrial contraction. In contrast, PAWP values reported in the literature are surrogates for left atrial pressures measured throughout the cardiac cycle and are reported to be reflective of mean LV diastolic pressures instead of LVEDP. In addition, as noted by authors, PAWP has been shown to better predict clinical outcomes in HFpEF compared with LVEDP.7 We have observed similar findings even in patients with single ventricle circulation.8 Thus, PAWP is felt by several groups and us to be a better metric of ventricular filling pressures than LVEDP as it reflects true pulmonary venous pressure.LVEDP is elevated in all patients with increased mean LV diastolic pressure, but the reverse is not always true. Mean LV diastolic pressure can be normal with elevated LVEDP. When atrial contraction contributes significantly to LV filling,9, 10 LVEDP can increase without an increase in mean LV diastolic pressure (Figure 1), which happens during an early stage of diastolic dysfunction with delayed LV relaxation resulting in a reduced LV filling during early diastole. This is the invasive correlate to grade 1 diastolic dysfunction assessed by echo‐Doppler. Grade 1 diastolic dysfunction is associated with a worse prognosis when compared with the presence of normal LV diastolic function. Thus, it is not surprising that the clinical outcomes of the patients with increased LVEDP are worse than in patients with normal values. However, hemodynamically, not all patients with increased LVEDP should be diagnosed with HFpEF. Typical examples are young patients with severe aortic regurgitation or hypertrophic cardiomyopathy. In these scenarios, it is not uncommon to observe large pulmonary vein atrial reversals (ie, elevated LVEDP) with normal E/e′ ratios and pulmonary pressures. Mean left atrial pressures remain normal, and the patients are asymptomatic despite the abnormal LV relaxation.Download figureDownload PowerPointFigure 1. Hemodynamic pressure tracing and Doppler mitral inflow in a patient with grade 1 diastolic dysfunction.A, LV pressure tracing and simultaneous Doppler recording of mitral inflow at rest from the same patient. LVEDP (arrow) is increased with normal left atrial pressure. Mitral inflow shows grade 1 diastolic dysfunction with marked increased velocity in atrial contraction. B, In the same patient, with exercise, mean LV diastolic pressure (PAWP) increases markedly with exercise. LA indicates left atrium; LV, left ventricle; LVEDP, left ventricle end‐diastolic pressure; MV, mitral valve; and PAWP, pulmonary arterial or capillary wedge pressure.However, patients with isolated increases in LVEDP are more prone to develop increased LV diastolic pressure with exercise to a degree to satisfy the definition of HFpEF (Figure 1). Although there are no data on mean LV diastolic pressure at rest and with exercise in the current paper, a significant portion of the patients with increased LVEDP would likely have developed an increased mean LV diastolic pressure with exercise if not already elevated at rest. From the echocardiography data in the study, the mitral inflow E velocity was lower than the A velocity indicating that some of the patients with increased LVEDP had grade 1 diastolic dysfunction with normal mean LV diastolic pressure. When we performed the first diastolic exercise echocardiography study, one third of the patients with grade 1 diastolic dysfunction (corresponding to an isolated increase in LVEDP) developed increased mean LV diastolic pressure estimated by E/e′,11 and two thirds did not.Based on the points discussed, one can argue that LVEDP would be a more sensitive metric of diastolic dysfunction than PAWP. However, it is mandatory to acknowledge some important aspects of invasive hemodynamic assessment: (1) LVEDP measurement, by definition, mandates arterial catheterization, which carries inherent risks when compared with venous catheterization; (2) in more advanced stages of diastolic dysfunction and/or in those with prominent PAWP v‐wave, LVEDP tends to be lower than PAWP; and (3) as observed in the present cohort, some degree of elevation in LVEDP in nearly universal in patients with suspected HFpEF (only 20% of patients had an LVEDP ≤15 mm Hg). Accordingly, considering data on the prognostic values of PAWP, it is our opinion that right heart catheterization and, particularly, exercise venous catheterization, remains the gold standard for the invasive hemodynamic assessment of ventricular filling pressures. The present results, however, do propose a role for routine measurement of LVEDP in patients with suspected HFpEF undergoing coronary angiography, as LV catheterization might provide additional diagnostic and prognostic information.Noninvasive Diagnosis of HFpEF in Clinical Practice and Role of Echo‐DopplerThe main message of the current paper is that measurement of LV filling pressure, even with LVEDP, is superior or at least incremental to the HFA‐PEFF score in predicting clinical outcomes. In more than half of the patients in the study, the HFA‐PEFF score was intermediate. Increased LVEDP was associated with a significantly higher risk of death and HF rehospitalization compared with the patients with normal LVEDP. The most recent expert consensus from the European Society of Cardiology proposed multimodality imaging and hemodynamic assessment for detection of the patients with HFpEF.12 The ultimate evidence for HFpEF is elevated LV filling pressure at rest or with exercise, which authors of the current study have attempted to do using LVEDP. As stated earlier, it would have been better to have the data on mean LV diastolic pressure at rest and with exercise. It will also be clinically helpful to know how many patients with increased LVEDP had normal mean diastolic pressure and its response to exercise to better classify the patients. It is hoped that the investigators of the current study will gather those data prospectively.Usually, in our clinical practice, the first diagnostic study in patients with suspected HFpEF is echocardiography. When these patients are referred to the echocardiography laboratory, they often already have at least an intermediate probability of HFpEF. The diagnosis of HFpEF relies on detecting increased filling pressure at rest or with exercise. The American Society of Echocardiography and the European Association of Cardiovascular Imaging guideline for diastolic function assessment recommends 4 parameters,5 but E/e′ is the most straightforward parameter that the HFpEF guidelines and scoring algorithms have adopted. The cutoff value of E/e′ for estimating increased mean LV diastolic pressure varies from 9 to 15 using the medial e′ velocity.2, 3 We should be mindful that the E/e′ ≥15 was very specific for mean LV diastolic pressure >12 mm Hg. However, its sensitivity was <50% in our first simultaneous echo‐catheterization diastolic filling pressure correlation study.13 When we performed an exercise echocardiography study in healthy subjects, the mean E/e′ was 6 and rarely >10, which was confirmed by a subsequent study14, 15 in young trained and untrained subjects. A simultaneous echo‐catheterization exercise study showed that E/e′ >10 was sensitive and specific for detecting PAWP ≥25 mm Hg with exercise, which is the hemodynamic definition of HFpEF.16 In patients with atrial fibrillation, E/e′ >11 was shown to correlate with increased filling pressure.17 Therefore, there should be a suspicion of increased LV filling pressure if E/e′ >10, especially when tricuspid regurgitation velocity is ≥2.8 m/sec at rest or 3.0 m/sec with exercise.Although E/e′ is a simple measure for estimating LV filling pressure, there are many circumstances when it may be unreliable, including mitral annulus calcification, conduction delay, regional wall motion abnormalities, high output state, or constrictive pericarditis.18, 19 However, recognizing the limitation of E/e′ in these conditions and utilization of other parameters can help decide whether the filling pressure is elevated. Left atrial reservoir strain has been shown to be a promising parameter as a tie‐breaker using ≤18% to 24% as a cutoff for increased filling pressure.12, 20 It would be very plausible that left atrial reservoir strain can replace the left atrial volume index as a primary index to estimate filling pressure in the next revised guideline, as illustrated in Figure 2. As the current study indicates, patients should undergo invasive hemodynamic assessment if there is any doubt in the echocardiographic determination of LV filling pressure or the diagnosis of HFpEF. However, a more comprehensive hemodynamic study should be performed to measure mean LV diastolic pressure by PAWP and pulmonary artery systolic pressure at rest and with exercise to detect the patients with HFpEF and also prognosticate and manage these patients.Download figureDownload PowerPointFigure 2. A proposed new algorithm to detect increased mean LV diastolic pressure and diagnose HFpEF.Almost all patients with HFpEF have diastolic dysfunction, that is, reduced mitral annulus e′ velocity. Therefore, diagnostic algorithms start with e′ velocity. *Mitral annulus calcification (MAC) represents patients in whom velocity is not reliable with very high probability of diastolic dysfunction. **When E/e >15 with exercise, PCWP ≥15 mm Hg at rest, or ≥25 mm Hg with exercise, then the diagnosis of HFpEF can be established. HFpEF indicates heart failure with preserved ejection fraction; IFP, increased filling pressure; LAS, left atrial reservoir strain; LVEF, left ventricular ejection fraction; NFP, normal filling pressure; PAWP, pulmonary artery wedge pressure; and TR, tricuspid regurgitation.DisclosuresNone.Footnotes*Correspondence to: Jae K. Oh, MD, Department of Cardiovascular Medicine Mayo Clinic 200 1st Street SW, Rochester, MN 55905. Email: oh.[email protected]eduFor Disclosures, see page 4.See Article by Choi et al.REFERENCES1 Choi KH, Yang JH, Seo JH, Hong D, Youn TH, Joh HS, Lee SH, Kim D, Park TK, Lee JM, et al. Role of invasive LVEDP measurement in HFpEF. J Am Heart Assoc.2023. doi: 10.1161/JAHA.122.027581LinkGoogle Scholar2 Pieske B, Tschope C, de Boer RA, Fraser AG, Anker SD, Donal E, Edelmann F, Fu M, Guazzi M, Lam CSP, et al. How to diagnose heart failure with preserved ejection fraction: the HFA‐PEFF diagnostic algorithm: a consensus recommendation from the Heart Failure Association (HFA) of the European Society of Cardiology (ESC). Eur Heart J.2019; 40:3297–3317. doi: 10.1093/eurheartj/ehz641CrossrefMedlineGoogle Scholar3 Reddy YNV, Carter RE, Obokata M, Redfield MM, Borlaug BA. A simple, evidence‐based approach to help guide diagnosis of heart failure with preserved ejection fraction. 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Published on behalf of the American Heart Association, Inc., by Wiley BlackwellThis is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.https://doi.org/10.1161/JAHA.122.028867PMID: 36892047 Originally publishedMarch 9, 2023 Keywordsheart failureautonomic nervous system diseasesstroke volumeEditorialsPDF download SubjectsDiagnostic TestingEchocardiographyHeart Failure