scholarly journals The haemodynamic basis of lung congestion during exercise in heart failure with preserved ejection fraction

Author(s):  
Yogesh N V Reddy ◽  
Masaru Obokata ◽  
Brandon Wiley ◽  
Katlyn E Koepp ◽  
Caitlin C Jorgenson ◽  
...  

Abstract Aims Increases in extravascular lung water (EVLW) during exercise contribute to symptoms, morbidity, and mortality in patients with heart failure and preserved ejection fraction (HFpEF), but the mechanisms leading to pulmonary congestion during exercise are not well-understood. Methods and results Compensated, ambulatory patients with HFpEF (n = 61) underwent invasive haemodynamic exercise testing using high-fidelity micromanometers with simultaneous lung ultrasound, echocardiography, and expired gas analysis at rest and during submaximal exercise. The presence or absence of EVLW was determined by lung ultrasound to evaluate for sonographic B-line artefacts. An increase in EVLW during exercise was observed in 33 patients (HFpEFLW+, 54%), while 28 (46%) did not develop EVLW (HFpEFLW−). Resting left ventricular function was similar in the groups, but right ventricular (RV) dysfunction was two-fold more common in HFpEFLW+ (64 vs. 31%), with lower RV systolic velocity and RV fractional area change. As compared to HFpEFLW−, the HFpEFLW+ group displayed higher pulmonary capillary wedge pressure (PCWP), higher pulmonary artery (PA) pressures, worse RV-PA coupling, and higher right atrial (RA) pressures during exercise, with increased haemoconcentration indicating greater loss of water from the vascular space. The development of lung congestion during exercise was significantly associated with elevations in PCWP and RA pressure as well as impairments in RV-PA coupling (area under the curve values 0.76–0.84). Conclusion Over half of stable outpatients with HFpEF develop increases in interstitial lung water, even during submaximal exercise. The acute development of lung congestion is correlated with increases in pulmonary capillary hydrostatic pressure that favours fluid filtration, and systemic venous hypertension due to altered RV-PA coupling, which may interfere with fluid clearance. Clinical trial registration NCT02885636.

2016 ◽  
Vol 35 (4) ◽  
pp. 207-214 ◽  
Author(s):  
Ibadete Bytyçi ◽  
Edmond Haliti ◽  
Gëzim Berisha ◽  
Arbërie Tishukaj ◽  
Faik Shatri ◽  
...  

2018 ◽  
Vol 9 (2) ◽  
pp. 83-91 ◽  
Author(s):  
Kevin Bryan Lo ◽  
Kene Mezue ◽  
Pradhum Ram ◽  
Abhinav Goyal ◽  
Mahek Shah ◽  
...  

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.


2015 ◽  
Vol 309 (9) ◽  
pp. H1407-H1418 ◽  
Author(s):  
Michael Schwarzl ◽  
Nazha Hamdani ◽  
Sebastian Seiler ◽  
Alessio Alogna ◽  
Martin Manninger ◽  
...  

Heart failure with preserved ejection fraction (HFPEF) evolves with the accumulation of risk factors. Relevant animal models to identify potential therapeutic targets and to test novel therapies for HFPEF are missing. We induced hypertension and hyperlipidemia in landrace pigs ( n = 8) by deoxycorticosteroneacetate (DOCA, 100 mg/kg, 90-day-release subcutaneous depot) and a Western diet (WD) containing high amounts of salt, fat, cholesterol, and sugar for 12 wk. Compared with weight-matched controls ( n = 8), DOCA/WD-treated pigs showed left ventricular (LV) concentric hypertrophy and left atrial dilatation in the absence of significant changes in LV ejection fraction or symptoms of heart failure at rest. The LV end-diastolic pressure-volume relationship was markedly shifted leftward. During simultaneous right atrial pacing and dobutamine infusion, cardiac output reserve and LV peak inflow velocities were lower in DOCA/WD-treated pigs at higher LV end-diastolic pressures. In LV biopsies, we observed myocyte hypertrophy, a shift toward the stiffer titin isoform N2B, and reduced total titin phosphorylation. LV superoxide production was increased, in part attributable to nitric oxide synthase (NOS) uncoupling, whereas AKT and NOS isoform expression and phosphorylation were unchanged. In conclusion, we developed a large-animal model in which loss of LV capacitance was associated with a titin isoform shift and dysfunctional NOS, in the presence of preserved LV ejection fraction. Our findings identify potential targets for the treatment of HFPEF in a relevant large-animal model.


2021 ◽  
Vol 8 ◽  
Author(s):  
Simon Lebek ◽  
Philipp Hegner ◽  
Maria Tafelmeier ◽  
Leopold Rupprecht ◽  
Christof Schmid ◽  
...  

Objective: Sleep-disordered breathing (SDB) is a widespread disease that is often associated with heart failure (HF) with preserved ejection fraction (HFpEF). HFpEF is more frequent in women than in men, but detailed pathomechanisms remain unclear. We investigated HFpEF in women and men in a high-risk cohort with SDB monitoring.Methods and Results: Three hundred twenty-seven patients (84.4% men) undergoing elective coronary artery bypass grafting were prospectively subjected to SDB monitoring, and an apnea–hypopnea index (AHI) ≥15/h defined SDB. HF was classified according to current guidelines. HFpEF was significantly more frequent in SDB patients compared to those without SDB (28 vs. 17%, P = 0.016). This distribution was driven by an increased frequency of HFpEF in female SDB patients (48% vs. only 25% in male, P = 0.022). In accordance, female patients with SDB exhibited significantly more impaired diastolic left ventricular filling compared to men (echocardiographic E/e′). In contrast to men, in women, minimum oxygen saturation (O2min, measured by polygraphy, R2 = 0.470, P &lt; 0.001) and time of oxygen saturation &lt;90% (R2 = 0.165, P = 0.044) were significantly correlated with E/e′. Moreover, the correlation between O2min and E/e′ was significantly different in women compared to men (P &lt; 0.001). Intriguingly, this association remained independent of clinical covariates in women [age, body mass index, systolic contractile dysfunction, diabetes mellitus, and glomerular filtration rate (GFR), R2 = 0.534, P = 0.042, multivariate regression analysis]. Since angiotensin II signaling has been mechanistically linked to HF, we measured protein expression of its cleavage enzyme ACE2 in human right atrial appendage biopsies (Western blot). Intriguingly, we found a significantly decreased ACE2 expression preferentially in women with SDB (2.66 ± 0.42 vs. 4.01 ± 2.47 in men with SDB, P = 0.005). In accordance, left ventricular mass index was significantly increased in women with SDB compared to women without SDB.Conclusion: In patients with SDB, HFpEF and diastolic dysfunction were more frequent in women compared to men. In contrast to men, the severity of SDB was associated with the degree of diastolic dysfunction in women. These insights might help to find sex-specific therapies for patients with sleep-disordered breathing and heart failure.Clinical Trial Registration: Unique identifier: NCT02877745, URL: http://www.clinicaltrials.gov.


Author(s):  
David M. Kaye ◽  
Emil Wolsk ◽  
Shane Nanayakkara ◽  
Justin Mariani ◽  
Christian Hassager ◽  
...  

Background Although a rapid rise in left atrial pressure during exertion is considered pathognomonic of heart failure with preserved ejection fraction (HFpEF), the fundamental circulatory determinants of this response are not clear, impacting upon the development of more effective therapies. We aimed to comprehensively describe the circulatory mechanics of patients with HFpEF at rest and during exercise in comparison with controls. Methods and Results We performed simultaneous right‐heart catheterization and echocardiography at rest and during exercise in 22 healthy control volunteers and 60 patients with confirmed HFpEF. Using detailed individual patient‐level hemodynamic and left ventricular ejection fraction data we performed computer simulations to evaluate the circulatory parameters including the estimated stressed blood volumethat contribute to the resting and exercise pulmonary capillary pressure. At rest and during exercise, left ventricular stiffness (V 30 , the end‐diastolic pressure–volume relationship at a filling pressure of 30 mm Hg), left ventricular elastance, and arterial elastance were all significantly greater in HFpEF than in controls. Stressed blood volume was significantly greater in HFpEF (26.9±5.4 versus 20.2±4.7 mL/kg, P <0.001), becoming even more pronounced during exercise (40.9±3.7 versus 27.5±7.0 mL per 70 kg, P <0.001). During exercise, the magnitude of the change in stressed blood volume ( r =0.67, P <0.001) and left ventricular stiffness ( r =−0.44, P <0.001) were key determinants of the rise in pulmonary capillary wedge pressure. Further detailed modeling studies showed that the hemodynamic response to exercise results from a complex non‐linear interaction between circulatory parameters. Conclusions The circulatory determinants of HFpEF physiology are complex. We identified stressed blood volume at rest and during exercise is a novel, key factor, therebyrepresenting an important potential therapeutic target.


Cardiology ◽  
2021 ◽  
pp. 1-8
Author(s):  
Ravi Rasalingam ◽  
Rachel Parker ◽  
Katherine E. Kurgansky ◽  
Luc Djousse ◽  
David Gagnon ◽  
...  

<b><i>Introduction:</i></b> Worsening renal function (WRF) predicts poor prognosis in patients with left ventricular systolic dysfunction. The effect of WRF in heart failure with preserved ejection fraction (HFpEF) is unclear. <b><i>Objective:</i></b> The objective of this study was to determine whether WRF during index hospitalization for HFpEF is associated with increased death or readmission for heart failure. <b><i>Methods:</i></b> National Veterans Affairs electronic medical data recorded between January 1, 2002, and December 31, 2014, were screened to identify index hospitalizations for HFpEF using an iterative algorithm. Patients were divided into 3 groups based on changes in serum Cr (sCr) during this admission. WRF was defined as a rise in sCr ≥0.3 mg/dL. Group 1 had no evidence of WRF, group 2 had transient WRF, and group 3 had persistent WRF at the time of discharge. <b><i>Results:</i></b> A total of 10,902 patients with index hospitalizations for HFpEF were identified (mean age 72, 97% male). Twenty-nine percent had WRF during this hospital admission, with 48% showing recovery of sCr and 52% with no recovery at discharge. The mortality rate over a mean follow-up duration of 3.26 years was 72%. Compared to group 1, groups 2 and 3 showed no significant difference in risk of death from any cause (hazard ratio [HR] = 0.95 [95% confidence interval [CI]: 0.87, 1.03] and 1.02 [95% CI: 0.93, 1.11], respectively), days hospitalized for any cause (incidence density ratio [IDR] = 1.01 [95% CI: 0.92, 1.11] and 1.01 [95% CI: 0.93, 1.11], respectively), or days hospitalized for heart failure (IDR = 0.94 [95% CI: 0.80, 1.10] and 0.94 [95% CI: 0.81, 1.09], respectively) in analyses adjusted for covariates affecting renal function and outcomes. <b><i>Conclusions:</i></b> While there is a high incidence of WRF during index hospitalizations for HFpEF, WRF is not associated with an increased risk of death or hospitalization. This suggests that WRF alone should not influence decisions regarding heart failure management.


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