138 Exercise haemodynamics in heart failure with preserved ejection fraction: a systematic review and meta-analysis

Abstract Aims Exercise right heart catheterization (RHC) is considered the gold-standard test to diagnose heart failure with preserved ejection fraction (HFpEF). However, exercise RHC is an insufficiently standardized technique, and current haemodynamic thresholds to define HFpEF are not universally accepted. We sought to describe the exercise haemodynamics profile of HFpEF cohorts reported in literature, as compared with control subjects. Methods and results We performed a systematic literature review until December 2020. Studies reporting pulmonary artery wedge pressure (PAWP) at rest and peak exercise were extracted. Summary estimates of all haemodynamic variables were evaluated, stratified according to body position (supine/upright exercise), and the PAWP/cardiac output (CO) slope during exercise was extrapolated. Twenty-eight studies were identified, providing data for 2230 HFpEF patients and 706 controls. At peak exercise, patients with HFpEF achieved higher PAWP [30 (29–31) vs. 16 (15–17) mmHg, P < 0.001] and mean right atrial pressure (P < 0.001) than controls. These differences persisted after adjustment for age, sex, body mass index, body position. However, peak PAWP values were highly heterogeneous among the cohorts, with a relative overlap with controls. PAWP/CO slope was steeper in HFpEF than in controls [3.81 (3.24–4.38) vs. 0.91 (0.24–1.58) mmHg/l/min, P < 0.001], even after adjustment for covariates (P = 0.020) (Figure). Conclusions The haemodynamic profile of HFpEF patients is consistent across studies and characterized by a higher left and right filling pressure at rest, magnified by physical exercise. Our analysis strongly suggests that PAWP/CO slope might allow for a more consistent identification of HFpEF, irrespective of body position. This variable likely overcomes the shortcomings of an isolated peak PAWP measurement, allowing for a more univocal identification of HFpEF in patients with unexplained dyspnoea.

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Abstract 15161: Increased Right Atrial Stiffness in Patients With Heart Failure With Preserved Ejection Fraction and Pulmonary Hypertension

Circulation ◽

10.1161/circ.142.suppl_3.15161 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Jessie van Wezenbeek ◽

Arno van der Bovenkamp ◽

Jeroen N Wessels ◽

Sophia-Anastasia Mouratoglou ◽

Marie Jose Goumans ◽

...

Keyword(s):

Heart Failure ◽

Pulmonary Hypertension ◽

Ejection Fraction ◽

Right Heart Catheterization ◽

Right Atrial ◽

Heart Catheterization ◽

Preserved Ejection Fraction ◽

Chamber View ◽

Patients With Heart Failure ◽

Pulmonary Arterial

Background: Patients with Heart Failure with preserved Ejection Fraction (HFpEF) and Pulmonary Hypertension (PH) have increased right atrial (RA) pressures. Whether the higher RA pressures are related to increased afterload or overall stiffening of the heart is unknown. The aim of this study is to gain further insight into the right atrium in HFpEF-PH. Methods: This is a retrospective analysis of patients with HFpEF (no PH), HFpEF-PH and Pulmonary Arterial Hypertension (PAH) that underwent right heart catheterization and cardiac magnetic resonance (CMR) imaging. CMR was used to determine RA function by quantifying volume and strain on the 4-chamber view. Total, passive and active RA emptying fraction (RAEF) were calculated. RA stiffness was calculated by determining the slope of maximum and minimum pressure during v-wave and minimal and maximal RA volumes. Groups were compared with ANOVA and post-hoc comparison with Bonferroni correction. Results: 176 patients were included: 13 HFpEF, 33 HFpEF-PH and 130 PAH patients. Although afterload was lower in PAH and higher in HFpEF patients, as shown by mean pulmonary arterial pressure (mPAP) (41 ± 2 mmHg in HFpEF-PH vs 53 ± 21 mmHg in PAH vs 19 ± 1 mmHg in HFpEF, p<0.001) and pulmonary vascular resistance (PVR) (2.3 ± 0.3 wu/m 2 in HFpEF-PH vs 5.7 ± 0.2 wu/m 2 in PAH vs 0.4 ± 0.06 wu/m 2 in HFpEF, p<0.001), mean RA pressure was significantly higher in HFpEF-PH patients compared to both groups (Figure 1A). HFpEF-PH patients had significantly increased RA stiffness compared to HFpEF and PAH patients (Figure 1B). Total RAEF was reduced in HFpEF-PH compared to PAH and HFpEF patients: passive RAEF was similar, but active RAEF was slightly reduced in HFpEF-PH (Figure 1C). This was in line with measurements of RA longitudinal strain (Figure 1D). Conclusions: Despite lower afterload, HFpEF-PH patients have worse RA function and increased RA stiffness compared to PAH. Higher RA pressures in HFpEF-PH may reflect additional stiffening of the heart.

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Abstract 17168: Myocardial Natriuretic Peptide Expression in Heart Failure With Preserved Ejection Fraction

Circulation ◽

10.1161/circ.142.suppl_3.17168 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Virginia S Hahn ◽

Hildur Knutsdottir ◽

Kenneth C Bedi ◽

Kenneth B Margulies ◽

Saptarsi M Haldar ◽

...

Keyword(s):

Gene Expression ◽

Heart Failure ◽

Renal Function ◽

Ejection Fraction ◽

Systolic Pressure ◽

Principal Component ◽

Serum Levels ◽

Right Heart Catheterization ◽

Heart Catheterization ◽

Preserved Ejection Fraction

Introduction: Serum natriuretic peptides (NP) are reduced in heart failure with preserved ejection fraction (HFpEF) compared to HFrEF; however, myocardial NP expression in HFpEF is unknown. We analyzed serum NTproBNP and myocardial RNAseq data to test the hypothesis that 1) lower myocardial NP expression in HFpEF drives the difference in serum levels, and 2) HFpEF with higher NP expression have transcriptomic signatures more similar to HFrEF. Methods: HFpEF patients (n=41) with clinical HF, LVEF≥50%, and meeting current consensus criteria for HFpEF underwent right heart catheterization and right ventricular (RV) endomyocardial biopsy. We performed differential gene expression analysis of RV septal tissue from HFpEF and compared to explanted HFrEF (n=30) and unused donor hearts (n=24, Control). Results: Myocardial NPPB expression was 5-fold higher in HFrEF vs Control (p<0.001) and unchanged in HFpEF vs Control, while NPPA expression was 9-fold higher in HFrEF and 5-fold higher in HFpEF vs Control (p<0.0001 for both comparisons). After adjustment for renal function and BMI, myocardial NPPB expression was significantly associated with serum NTproBNP in HFpEF (R 2 0.68; p<0.0001 for renal function, NPPB expression; p=0.03 for BMI). Pulmonary artery (PA) systolic pressure and PA wedge pressure correlated with myocardial NPPB expression (PASP R 2 0.45, p<0.0001; PAWP R 2 0.25, p=0.01), even after adjustment for comorbidities. HFpEF patients with high (≥ median NPPB expression in HFpEF) vs low NPPB expression had transcriptomic signatures more similar to HFrEF using ~13,000 genes in a Principal Component Analysis (Figure), quantified by vector distance from HFrEF (p=0.017). Conclusions: HFpEF patients have reduced serum NTproBNP due to lower myocardial NPPB gene expression. HFpEF patients with higher NPPB expression have transcriptomic signatures more similar to HFrEF, highlighting a HFpEF subgroup that may benefit from targeted therapies.

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Pulmonary Gas Transfer Dysfunction During Exercise Right Heart Catheterization in Heart Failure with Preserved Ejection Fraction: Do Lung Diffusion Limitations Contribute to the Pathogenesis of Exercise Intolerance?

10.1164/ajrccm-conference.2020.201.1_meetingabstracts.a2072 ◽

2020 ◽

Author(s):

G.M. Stewart ◽

C.C. Fermoyle ◽

B.A. Borlaug ◽

B.D. Johnson

Keyword(s):

Heart Failure ◽

Ejection Fraction ◽

Right Heart Catheterization ◽

Exercise Intolerance ◽

Heart Catheterization ◽

Gas Transfer ◽

Preserved Ejection Fraction ◽

Right Heart ◽

Lung Diffusion ◽

Diffusion Limitations

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Clinical characteristics and prognostic impact of pulmonary hypertension in heart failure with preserved ejection fraction: the PURSUIT HFpEF study

European Heart Journal ◽

10.1093/ehjci/ehaa946.2286 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

F Sera ◽

T Ohtani ◽

K Nakamoto ◽

T Yamada ◽

Y Yasumura ◽

...

Keyword(s):

Heart Failure ◽

Pulmonary Hypertension ◽

Ejection Fraction ◽

Right Atrial ◽

Rank Test ◽

Heart Catheterization ◽

Funding Source ◽

Prognostic Impact ◽

Preserved Ejection Fraction ◽

Private Company

Abstract Background Heart failure (HF) with preserved ejection fraction (HFpEF) can develop pulmonary hypertension (PH), which can result from pre-capillary PH as well as post-capillary PH. However, the prevalence and clinical significance of pre-capillary component of PH in HFpEF remain unknown. Purpose We aimed to investigate prevalence, clinical features, and prognostic impact of pre-capillary and/or post capillary PH associated with HFpEF. Methods From the PURSUIT-HFpEF (Prospective Multicenter Observational Study of Patients with Heart Failure with Preserved Ejection Fraction) registry, 204 patients (men: 46%, age: 79±9 years) who were hospitalized with HF and underwent right heart catheterization were divided into 4 groups according to the PH guidelines: non-PH, isolated post-capillary PH (Ipc-PH), pre-capillary PH, and combined pre- and post-capillary PH (Cpc-PH). Patients who had been diagnosed with idiopathic pulmonary arterial hypertension were excluded from the analysis. Results The prevalence of PH was 31% (Ipc-PH: 22%, pre-capillary PH: 3%, Cpc-PH: 6%). The prevalence of subcategories of PH was significantly different depending on mean right atrial pressure (RAP) (figure). Echocardiography at discharge showed no significant differences in RV diameter or TAPSE, but smaller LV diameter and higher E/e' in pre-capillary PH and Cpc-PH, which resulted in a higher operant diastolic elastance (Ed). Composite endpoint of all-cause mortality and HF hospitalization at 1 year occurred 13% in non-PH, 25% in Ipc-PH, 49% in pre-capillary PH, and 63% in Cpc-PH, respectively (p=0.001 by log-rank test). Conclusions Distinct prevalence of PH was observed in the groups with different RAP levels. Pre-capillary component of PH was associated with impaired LV diastolic function and worse outcomes in HFpEF. Figure 1 Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Roche Diagnostics K.K.; Fuji Film Toyama Chemical Co. Ltd

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The diagnostic value of passive leg raise during right heart catheterization in diagnosing heart failure with preserved ejection fraction

European Heart Journal ◽

10.1093/ehjci/ehaa946.0851 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

A.A Van De Bovenkamp ◽

N Wijkstra ◽

N.J Braams ◽

M.A Jansen ◽

F.P.T Oosterveer ◽

...

Keyword(s):

Heart Failure ◽

Ejection Fraction ◽

Gold Standard ◽

Diagnostic Value ◽

Right Heart Catheterization ◽

Heart Catheterization ◽

Preserved Ejection Fraction ◽

Right Heart ◽

Passive Leg Raise ◽

Invasive Measurement

Abstract Background Heart failure with preserved ejection fraction (HFpEF) is a frequent and disabling disease, but can be difficult to diagnose. Due to limited sensitivity of non-invasive evaluation of left ventricular (LV) diastolic dysfunction, invasive measurement may be warranted. The gold standard for diagnosing HFpEF is invasive measurement of LV end-diastolic pressure or its surrogate pulmonary capillary wedge pressure (PCWP). In case of normal LV filling pressures at rest (PCWP@rest <16 mmHg), patients should undergo stress testing to unmask occult HFpEF (early HFpEF if PCWP@exercise ≥25mmHg). Performing exercise during a right heart catheterization is time-consuming and logistically challenging. Passive leg raise increases venous return and can lead to an abnormal increase in LV filling pressures in case of diastolic dysfunction. Whether this leg raise maneuver (PCWP@legraise) can be used as an accurate method to diagnose or exclude HFpEF and what cut-off values should be used is unknown. Purpose To assess the diagnostic value of PCWP@legraise during right heart catheterization for HFpEF. Methods We reviewed all consecutive patients who received a diagnostic right heart catheterization with PCWP-measurements at rest, passive leg raise and during exercise (minimally >40% peak VO2) between 2017 and 2020 in a tertiary medical center (n=124). Zero reference point was defined mid-thorax. PCWP was measured end-expiratory mid A-wave. Patients with insufficient data (n=17), uninterpretable tracings (n=13) or PCWP@rest >16 mmHg were excluded (n=19). The diagnostic value of PCWP@legraise was compared to the gold standard for HFpEF (PCWP@exercise). Results We analyzed 75 patients, with a mean age of 58 (±16) years, female (60%), mean BMI 27.8 (±5.5). HFpEF was diagnosed in 47% of the cases, non-HFpEF existed of pulmonary arterial hypertension (23%), chronic thrombo-embolic disease (15%) or other (15%). Figure 1A shows PCWP@rest, PCWP@legraise, PCWP@exercise for HFpEF and non-HFpEF. The diagnostic performance of PCWP@legraise was higher than PCWP@rest (Figure 1B; AUC 0.83 vs 0.75). PCWP@legraise ≥22 mmHg had a specificity of 100% and a positive predictive value of 100% for diagnosing HFpEF and could be used as a cut-off for diagnosing HFpEF. PCWP@legraise of ≥13 mmHg had a sensitivity of 98% and a negative predictive value of 93%, and could be used as a cut-off for excluding HFpEF. If these cut-offs were used to refute or diagnose HFpEF, 17 patients (23%) could have been differed from exercise during right heart catheterization. The change in PCWP due to passive leg raise was of lower diagnostic value than the absolute value of PCWP@legraise. Conclusion In our cohort, the leg raise maneuver is of diagnostic value. With the proposed PCWP@legraise criteria for HFpEF - validated against the gold standard (PCWP@exercise) - the exercise could have been omitted in almost a quarter of the cases. More (external) validation is warranted. Figure 1 Funding Acknowledgement Type of funding source: None

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Echocardiographic and Hemodynamic Parameters Associated with Diminishing Renal Filtration among Patients with Heart Failure with Preserved Ejection Fraction

Cardiorenal Medicine ◽

10.1159/000494089 ◽

2018 ◽

Vol 9 (2) ◽

pp. 83-91 ◽

Cited By ~ 1

Author(s):

Kevin Bryan Lo ◽

Kene Mezue ◽

Pradhum Ram ◽

Abhinav Goyal ◽

Mahek Shah ◽

...

Keyword(s):

Heart Failure ◽

Ejection Fraction ◽

Renal Dysfunction ◽

Pressure Ratio ◽

Left Ventricular ◽

Right Atrial ◽

Heart Catheterization ◽

Preserved Ejection Fraction ◽

Patients With Heart Failure

Background: Renal dysfunction is an important predictor of poor outcomes in patients with heart failure with preserved ejection fraction (HFpEF). Right ventricular (RV) dysfunction is implicated as one of the explanations for worsening renal function in cardiorenal syndrome. Novel right heart catheterization (RHC) parameters such as pulmonary artery pulsatility index (PAPi) and right atrial to pulmonary capillary wedge pressure ratio (RA:PCWP) have been found as predictors of RV dysfunction. However, most studies investigating these parameters have been done in the setting of myocardial infarction or left ventricular assist device implantation, with limited data on these metrics in patients with HFpEF. Objective: The purpose of this study was to determine whether novel RHC parameters such as RA:PCWP and PAPi correlate with long-term renal outcomes among patients with HFpEF. Methods: A retrospective single-center study of adult patients with a documented diagnosis of heart failure who had RHC was performed between January 2006 and December 2010 at Einstein Med ical Center Philadelphia. Selected patients also had a serum B-type natriuretic peptide level ≥100 pg/mL and a PCWP ≥15 mm Hg. Patients with an ejection fraction < 50%, including those with recovered ejection fraction, and end-stage renal disease were excluded. Results: A total of 81 patients with a clinical diagnosis of HFpEF were identified who met the inclusion criteria. On multivariate analysis, after adjusting for age, sex, race, diabetes, hypertension, and cardiac index, PAPi was associated with long-term estimated glomerular filtration rate (eGFR) (β = 3.43, 95% CI = 0.635–6.23, p = 0.017), and RA:PCWP showed a trend towards significance (β = 14.81, 95% CI = –0.096–29.73, p = 0.051). The results were unchanged after further adjustment for eGFR at the time of RHC. Conclusion: Novel hemodynamic indices obtained by RHC may have predictive value for long-term renal dysfunction in patients with HFpEF.

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Diagnostic utility of sub-maximum cardiopulmonary exercise testing in the ambulatory setting for heart failure with preserved ejection fraction

Pulmonary Circulation ◽

10.1177/2045894020972273 ◽

2020 ◽

Vol 10 (4) ◽

pp. 204589402097227

Author(s):

Hannah T. Oakland ◽

Phillip Joseph ◽

Ahmed Elassal ◽

Marjorie Cullinan ◽

Paul M. Heerdt ◽

...

Keyword(s):

Heart Failure ◽

Pulmonary Hypertension ◽

Gas Exchange ◽

Ejection Fraction ◽

Exercise Test ◽

Cardiopulmonary Exercise Test ◽

Right Heart Catheterization ◽

Heart Catheterization ◽

Preserved Ejection Fraction ◽

Cardiopulmonary Exercise

Pulmonary hypertension is commonly associated with heart failure with preserved ejection fraction. In heart failure with preserved ejection fraction, the elevated left-sided filling pressures result in isolated post-capillary pulmonary hypertension or combined pre- and post-capillary pulmonary hypertension. Although right heart catheterization is the gold standard for diagnosis, it is an invasive test with associated risks. The ability of sub-maximum cardiopulmonary exercise test as an adjunct diagnostic tool in pulmonary hypertension-associated heart failure with preserved ejection fraction is not known. Forty-six patients with heart failure with preserved ejection fraction and pulmonary hypertension (27 patients with combined pre- and post-capillary pulmonary hypertension and 19 patients with isolated post-capillary pulmonary hypertension) underwent sub-maximum cardiopulmonary exercise test followed by right heart catheterization. The study also included 18 age- and gender-matched control subjects. Several sub-maximum gas exchange parameters were examined to determine the ability of sub-maximum cardiopulmonary exercise test to distinguish between isolated post-capillary pulmonary hypertension and combined pre- and post-capillary pulmonary hypertension. Conventional echocardiogram measures did not distinguish between isolated post-capillary pulmonary hypertension and combined pre- and post-capillary pulmonary hypertension. Compared to isolated post-capillary pulmonary hypertension, combined pre- and post-capillary pulmonary hypertension had greater ventilatory equivalent for carbon dioxide (VE/VCO2) slope, reduced delta end-tidal CO2 change during exercise, reduced oxygen uptake efficiency slope, and reduced gas exchange determined pulmonary vascular capacitance. The latter was significantly associated with right heart catheterization determined pulmonary artery compliance ( r = 0.5; p = 0.0004). On univariate analysis, sub-maximum VE/VCO2, delta end-tidal carbon dioxide, and gas exchange determined pulmonary vascular capacitance emerged as independent predictors of the extrapolated maximum oxygen uptake (%predicted) (β-coefficient values of –7.32, 95% CI: –13.3 – (–1.32), p = 0.01; 8.01, 95% CI: 1.96–14.05, p = 0.01; 8.78, 95% CI: 2.26–15.29, p = 0.01, respectively). Sub-maximum gas exchange parameters obtained during cardiopulmonary exercise test in an ambulatory setting allows for discrimination between isolated post-capillary pulmonary hypertension and combined pre- and post-capillary pulmonary hypertension. Additionally, sub-maximum cardiopulmonary exercise test derived VE/VCO2, delta end-tidal carbon dioxide, and gas exchange determined pulmonary vascular capacitance influences aerobic capacity in heart failure with preserved ejection fraction.

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Prognostic Importance of Pulmonary Arterial Capacitance in Acute Decompensated Heart Failure With Preserved Ejection Fraction

Journal of the American Heart Association ◽

10.1161/jaha.121.023043 ◽

2021 ◽

Author(s):

Akito Nakagawa ◽

Yoshio Yasumura ◽

Chikako Yoshida ◽

Takahiro Okumura ◽

Jun Tateishi ◽

...

Keyword(s):

Heart Failure ◽

Ejection Fraction ◽

Cox Regression ◽

Right Heart Catheterization ◽

Heart Catheterization ◽

Preserved Ejection Fraction ◽

Right Heart ◽

End Point ◽

Prognostic Importance ◽

Pulmonary Arterial

Background Although the prognostic importance of pulmonary arterial capacitance (PAC; stroke volume/pulmonary arterial pulse pressure) has been elucidated in heart failure with reduced ejection fraction, whether its significance in patients suffering from heart failure with preserved ejection fraction is not known. We aimed to examine the association of PAC with outcomes in inpatients with heart failure with preserved ejection fraction. Methods and Results We prospectively studied 705 patients (median age, 83 years; 55% women) registered in PURSUIT‐HFpEF (Prospective Multicenter Observational Study of Patients With Heart Failure With Preserved Ejection Fraction). We investigated the association of echocardiographic PAC at discharge with the primary end point of all‐cause death or heart failure rehospitalization with a mean follow‐up of 384 days. We further tested the acceptability of the prognostic significance of PAC in a subgroup of patients (167/705 patients; median age, 81 years; 53% women) in whom PAC was assessed by right heart catheterization. The median echocardiographic PAC was 2.52 mL/mm Hg, with a quartile range of 1.78 to 3.32 mL/mm Hg. Univariable and multivariable Cox regression testing revealed that echocardiographic PAC was associated with the primary end point (unadjusted hazard ratio, 0.82; 95% CI, 0.72–0.92; P =0.001; adjusted hazard ratio, 0.86; 95% CI, 0.74–0.99; P =0.035, respectively). Univariable Cox regression testing revealed that PAC assessed by right heart catheterization (median calculated PAC, 2.82 mL/mm Hg) was also associated with the primary end point (unadjusted HR, 0.70; 95% CI, 0.52–0.91; P =0.005). Conclusions A prospective cohort study revealed that impaired PAC diagnosed with both echocardiography and right heart catheterization was associated with adverse outcomes in inpatients with heart failure with preserved ejection fraction. Registration URL: https://upload.umin.ac.jp/cgi‐open‐bin/ctr_e/ctr_view.cgi?recptno=R000024414. Unique identifier: UMIN000021831.

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