scholarly journals Congestive heart failure with preserved ejection fraction is associated with severely impaired dynamic Starling mechanism

2011 ◽  
Vol 110 (4) ◽  
pp. 964-971 ◽  
Author(s):  
Shigeki Shibata ◽  
Jeff L. Hastings ◽  
Anand Prasad ◽  
Qi Fu ◽  
Paul S. Bhella ◽  
...  
Keyword(s):  
Heart Failure ◽  
Congestive Heart Failure ◽  
Transfer Function ◽  
Arterial Stiffness ◽  
Ejection Fraction ◽  
Diastolic Pressure ◽  
Left Ventricular ◽  
Preserved Ejection Fraction ◽  
Transfer Function Analysis ◽  
And Control

Sedentary aging leads to increased cardiovascular stiffening, which can be ameliorated by sufficient amounts of lifelong exercise training. An even more extreme form of cardiovascular stiffening can be seen in heart failure with preserved ejection fraction (HFpEF), which comprises ∼40∼50% of elderly patients diagnosed with congestive heart failure. There are two major interrelated hypotheses proposed to explain heart failure in these patients: 1) increased left ventricular (LV) diastolic stiffness and 2) increased arterial stiffening. The beat-to-beat dynamic Starling mechanism, which is impaired with healthy human aging, reflects the interaction between ventricular and arterial stiffness and thus may provide a link between these two mechanisms underlying HFpEF. Spectral transfer function analysis was applied between beat-to-beat changes in LV end-diastolic pressure (LVEDP; estimated from pulmonary artery diastolic pressure with a right heart catheter) and stroke volume (SV) index. The dynamic Starling mechanism (transfer function gain between LVEDP and the SV index) was impaired in HFpEF patients ( n = 10) compared with healthy age-matched controls ( n = 12) (HFpEF: 0.23 ± 0.10 ml·m−2·mmHg−1 and control: 0.37 ± 0.11 ml·m−2·mmHg−1, means ± SD, P = 0.008). There was also a markedly increased (3-fold) fluctuation of LV filling pressures (power spectral density of LVEDP) in HFpEF patients, which may predispose to pulmonary edema due to intermittent exposure to higher pulmonary capillary pressure (HFpEF: 12.2 ± 10.4 mmHg2 and control: 3.8 ± 2.9 mmHg2, P = 0.014). An impaired dynamic Starling mechanism, even more extreme than that observed with healthy aging, is associated with marked breath-by-breath LVEDP variability and may reflect advanced ventricular and arterial stiffness in HFpEF, possibly contributing to reduced forward output and pulmonary congestion.

scholarly journals Spectral transfer function analysis of respiratory hemodynamic fluctuations predicts end-diastolic stiffness in preserved ejection fraction heart failure

2016 ◽  
Vol 310 (1) ◽  
pp. H4-H13 ◽  
Author(s):  
Mahmoud Abdellatif ◽  
Sara Leite ◽  
Mohamed Alaa ◽  
José Oliveira-Pinto ◽  
Marta Tavares-Silva ◽  
...  
Keyword(s):  
Heart Failure ◽  
Transfer Function ◽  
Ejection Fraction ◽  
Left Ventricular ◽  
Positive Pressure ◽  
Preserved Ejection Fraction ◽  
Operating Characteristics ◽  
Hemodynamic Evaluation ◽  
Transfer Function Analysis ◽  
Diastolic Stiffness

Preserved ejection fraction heart failure (HFpEF) diagnosis remains controversial, and invasive left ventricular (LV) hemodynamic evaluation and/or exercise testing is advocated by many. The stiffer HFpEF myocardium may show impaired stroke volume (SV) variation induced by fluctuating LV filling pressure during ventilation. Our aim was to investigate spectral transfer function (STF) gain from end-diastolic pressure (EDP) to indexed SV (SVi) in experimental HFpEF. Eighteen-week-old Wistar-Kyoto (WKY) and ZSF1 lean (ZSF1 Ln) and obese rats (ZSF1 Ob) randomly underwent LV open-chest (OC, n = 8 each group) or closed-chest hemodynamic evaluation (CC, n = 6 each group) under halogenate anesthesia and positive-pressure ventilation at constant inspiratory pressure. Beat-to-beat fluctuations in hemodynamic parameters during ventilation were assessed by STF. End-diastolic stiffness (βi) and end-systolic elastance (Eesi) for indexed volumes were obtained by inferior vena cava occlusion in OC (multibeat) or single-beat method estimates in CC. ZSF1 Ob showed higher EDP spectrum ( P < 0.001), higher STF gain between end-diastolic volume and EDP, and impaired STF gain between EDP and SVi compared with both hypertensive ZSF1 Ln and normotensive WKY controls ( P < 0.001). Likewise βi was only higher in ZSF1 Ob while Eesi was raised in both ZSF1 groups. On multivariate analysis βi and not Eesi correlated with impaired STF gain from EDP to SVi ( P < 0.001), and receiver-operating characteristics analysis showed an area under curve of 0.89 for higher βi prediction ( P < 0.001). Results support further clinical testing of STF analysis from right heart catheterization-derived EDP surrogates to noninvasively determined SV as screening/diagnostic tool to assess myocardial stiffness in HFpEF.

scholarly journals Preload-corrected dynamic Starling mechanism in patients with heart failure with preserved ejection fraction

2018 ◽  
Vol 124 (1) ◽  
pp. 76-82 ◽  
Author(s):  
Michinari Hieda ◽  
Erin Howden ◽  
Shigeki Shibata ◽  
Takashi Tarumi ◽  
Justin Lawley ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Diastolic Dysfunction ◽  
Diastolic Pressure ◽  
Left Ventricular Diastolic Dysfunction ◽  
Left Ventricular ◽  
Preserved Ejection Fraction ◽  
Dynamic Modulation ◽  
Power Spectral ◽  
Ventricular Diastolic Dysfunction

The beat-to-beat dynamic Starling mechanism (DSM), the dynamic modulation of stroke volume (SV) because of breath-by-breath changes in left-ventricular end-diastolic pressure (LVEDP), reflects ventricular-arterial coupling. The purpose of this study was to test whether the LVEDP-SV relationship remained impaired in heart failure with preserved ejection fraction (HFpEF) patients after normalization of LVEDP. Right heart catheterization and model-flow analysis of the arterial pressure waveform were performed while preload was manipulated using lower-body negative pressure to alter LVEDP. The DSM was compared at similar levels of LVEDP between HFpEF patients ( n = 10) and age-matched healthy controls ( n = 12) (HFpEF vs. controls: 10.9 ± 3.8 vs. 11.2 ± 1.3 mmHg, P = 1.00). Transfer function analysis between diastolic pulmonary artery pressure (PAD) representing dynamic changes in LVEDP vs. SV index was applied to obtain gain and coherence of the DSM. The DSM gain was significantly lower in HFpEF patients than in the controls, even at a similar level of LVEDP (0.46 ± 0.19 vs. 0.99 ± 0.39 ml·m−2·mmHg−1, P = 0.0018). Moreover, the power spectral density of PAD, the input variability, was greater in the HFpEF group than the controls (0.75 ± 0.38 vs. 0.28 ± 0.26 mmHg2, P = 0.01). Conversely, the power spectral density of SV index, the output variability, was not different between the groups ( P = 0.97). There was no difference in the coherence, which confirms the reliability of the linear transfer function between the two groups (0.71 ± 0.13 vs. 0.77 ± 0.19, P = 0.87). The DSM gain in HFpEF patients is impaired compared with age-matched controls even at a similar level of LVEDP, which may reflect intrinsic LV diastolic dysfunction and incompetence of ventricular-arterial coupling. NEW & NOTEWORTHY The beat-to-beat dynamic Starling mechanism (DSM), the dynamic modulation of stroke volume because of breath-by-breath changes in left-ventricular end-diastolic pressure (LVEDP), reflects ventricular-arterial coupling. Although the DSM gain is impaired in heart failure with preserved ejection fraction (HFpEF) patients, it is not clear whether this is because of higher LVEDP or left-ventricular diastolic dysfunction. The DSM gain in HFpEF patients is severely impaired, even at a similar level of LVEDP, which may reflect intrinsic left-ventricular diastolic dysfunction.

Abstract 15172: Murf1 Inhibitor Embl205 is a New Approach for Treatment of Heart Failure With Preserved Ejection Fraction in an Animal Model

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Anett Jannasch ◽  
Antje Schauer ◽  
Virginia Kirchhoff ◽  
Runa Draskowsi ◽  
Claudia Dittfeld ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Diastolic Pressure ◽  
Posterior Wall ◽  
Left Ventricular ◽  
Skeletal Muscle Atrophy ◽  
Lv Function ◽  
Preserved Ejection Fraction ◽  
The Impact ◽  
Peak Gradient

Background: The novel MuRF1 inhibitor EMBL205 attenuates effectively developing skeletal muscle atrophy and dysfunction in animals with heart failure with preserved ejection fraction (HFpEF, ZSF1 rat model). The impact of EMBL205 on myocardial function in the HFpEF setting is currently unknown and was evaluated in ZSF1 rats. Methods: 20 wks-old female obese ZSF1 rats received EMBL205 (12 wks, conc. of 0.1% in chow; HFpEF-EMBL205). Age-matched untreated lean (con) and obese (HFpEF) ZSF1 rats served as controls. At 32 wks of age left ventricular (LV)-, aortic valve (AV) function and LV end diastolic pressure (LVEDP) was determined by echocardiography and invasive hemodynamic measurements. LV expression of collagen 1A (Col1A) and 3A (Col3A) was assessed by qRT-PCR, MMP2 expression was obtained by zymography and perivascular fibrosis was quantified in histological sections. Results: Development of HFpEF in ZSF1 obese animals is associated with cardiac enlargement and hypertrophy, as evident by increased myocardial weight, an increase in end diastolic volume (EDV) and LV anterior and posterior wall diameters. Diastolic LV-function is disturbed with elevation of E/é, an increased LVEDP and a preserved LV ejection fraction. AV peak velocity and peak gradient are significantly increased and AV opening area (AVA) significantly decreased. Col1A and Col3A expression are increased in HFpEF animals. EMBL205 treatment results in a significant reduction of myocardial weight and a trend towards lower EDV compared to HFpEF group. EMBL205 attenuates the increase in E/é, LVEDP, AV peak gradient and the decrease of AVA. EMBL205 significantly reduces Col3A expression and a trend for Col1A expression is seen. Increased perivascular fibrosis and MMP2 expression in HFpEF is extenuated by EMBL205 treatment (table 1). Conclusions: Application of EMBL205 attenuated the development of pathological myocardial alterations associated with HFpEF in ZSF1rats due to antifibrotic effects.

Abstract 12325: Compensatory Increase of Left Atrial External Work to Left Ventricular Dysfunction During Afterload Increase: Insights Into the Mechanism of Decompensation in Heart Failure With Preserved Ejection Fraction

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Katsuji Inoue ◽  
Toshihiko Asanuma ◽  
Kasumi Masuda ◽  
Daisuke Sakurai ◽  
Masamichi Oka ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Diastolic Pressure ◽  
Systolic Pressure ◽  
Strain Curve ◽  
Left Ventricular ◽  
Preserved Ejection Fraction ◽  
External Work ◽  
Reservoir Function ◽  
Left Pulmonary Vein

Introduction: Afterload mismatch is considered as a cause of acute decompensation in patients with heart failure with preserved ejection fraction (HFPEF). However, behaviors of left atrium (LA) and ventricle (LV) to afterload increase have not been fully elucidated. We investigated how LA and LV acted to acute increase in afterload using speckle tracking echocardiography. Methods: Serial echocardiographic and hemodynamic data were acquired in 10 dogs during banding of the descending aorta (AoB). LA pressure was measured by a micromanometer via left pulmonary vein. As shown in Figure, peak negative strain during LA contraction and strain change during LA relaxation (early reservoir strain) and that during systole (late reservoir strain) were generated by simultaneous acquisition of LA longitudinal strain and volume. Pressure-strain curve showed 2 loops (A-loop, V-loop) and areas in A-loop and V-loop were computed as the work during active contraction and relaxation (A-work) and that during passive filling and emptying (V-work), respectively. Results: AoB increased LV systolic pressure by about 60 mmHg, mean LA pressure (3.8±1.3 vs. 7.1±2.0 mmHg) and LV end-diastolic pressure (4.5±1.7 vs. 10.7±4.0 mmHg, all p < 0.01). LV global circumferential strain decreased (-18.8±3.5 vs. -13.2±3.5%, p < 0.01) but LV stroke volume was maintained (8.4±2.3 vs. 9.6±3.6 ml). LA peak negative strain (-2.9±2.3 vs. -9.8±4.0%, p < 0.01) and early reservoir strain (3.4±1.1 vs. 7.8±2.6%, p < 0.01) increased substantially by AoB, but late reservoir function did not change (9.3±3.5 vs. 6.1±2.0%). A-work significantly increased (3.2±2.0 to 19.2±15.1 mmHg %, p < 0.01), while V-work did not change (13.3±7.1 vs. 13.6±8.0 mmHg %). Conclusions: During aortic banding, LA contraction, early reservoir function and thereby external work during the phase increased as a compensation to LV dysfunction. The failure of this mechanism may lead to decompensation in HFPEF.

Afterload-induced diastolic dysfunction contributes to high filling pressures in experimental heart failure with preserved ejection fraction

2015 ◽  
Vol 309 (10) ◽  
pp. H1648-H1654 ◽  
Author(s):  
Sara Leite ◽  
Sara Rodrigues ◽  
Marta Tavares-Silva ◽  
José Oliveira-Pinto ◽  
Mohamed Alaa ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Diastolic Pressure ◽  
Vena Cava ◽  
Left Ventricular ◽  
Preserved Ejection Fraction ◽  
Stiffness Constant ◽  
Complete Relaxation ◽  
Filling Time ◽  
Wistar Kyoto

Myocardial stiffness and upward-shifted end-diastolic pressure-volume (P-V) relationship (EDPVR) are the key to high filling pressures in heart failure with preserved ejection fraction (HFpEF). Nevertheless, many patients may remain asymptomatic unless hemodynamic stress is imposed on the myocardium. Whether delayed relaxation induced by pressure challenge may contribute to high end-diastolic pressure (EDP) remains unsettled. Our aim was to assess the effect of suddenly imposed isovolumic afterload on relaxation and EDP, exploiting a highly controlled P-V experimental evaluation setup in the ZSF1 obese rat (ZSF1 Ob) model of HFpEF. Twenty-week-old ZSF1 Ob ( n = 12), healthy Wistar-Kyoto rats (WKY, n = 11), and hypertensive ZSF1 lean control rats (ZSF1 Ln, n = 10) underwent open-thorax left ventricular (LV) P-V hemodynamic evaluation under anesthesia with sevoflurane. EDPVR was obtained by inferior vena cava occlusions to assess LV ED chamber stiffness constant β, and single-beat isovolumic afterload acquisitions were obtained by swift occlusions of the ascending aorta. ZSF1 Ob showed increased ED stiffness, delayed relaxation, as assessed by time constant of isovolumic relaxation (τ), and elevated EDP with normal ejection fraction. Isovolumic afterload increased EDP without concomitant changes in ED volume or heart rate. In isovolumic beats, relaxation was delayed to the extent that time for complete relaxation as predicted by 3.5 × monoexponentially derived τ (τexp) exceeded effective filling time. EDP elevation correlated with reduced time available to relax, which was the only independent predictor of EDP rise in multiple linear regression. Our results suggest that delayed relaxation during pressure challenge is an important contributor to lung congestion and effort intolerance in HFpEF.

Echocardiography and invasive hemodynamics during stress testing for diagnosis of heart failure with preserved ejection fraction: an experimental study

2015 ◽  
Vol 308 (12) ◽  
pp. H1556-H1563 ◽  
Author(s):  
Sara Leite ◽  
José Oliveira-Pinto ◽  
Marta Tavares-Silva ◽  
Mahmoud Abdellatif ◽  
Dulce Fontoura ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Diastolic Pressure ◽  
Characteristic Curve ◽  
Left Ventricular ◽  
Doppler Velocity ◽  
Preserved Ejection Fraction ◽  
Hemodynamic Stress ◽  
Effort Testing ◽  
Obese Rats

Inclusion of exercise testing in diagnostic guidelines for heart failure with preserved ejection fraction (HFpEF) has been advocated, but the target population, technical challenges, and underlying pathophysiological complexity raise difficulties to implementation. Hemodynamic stress tests may be feasible alternatives. Our aim was to test Trendelenburg positioning, phenylephrine, and dobutamine in the ZSF1 obese rat model to find echocardiographic surrogates for end-diastolic pressure (EDP) elevation and HFpEF. Seventeen-week-old Wistar-Kyoto, ZSF1 lean, and obese rats ( n = 7 each) randomly and sequentially underwent (crossover) Trendelenburg (30°), 5 μg·Kg−1·min−1 dobutamine, and 7.5 μg·Kg−1·min−1 phenylephrine with simultaneous left ventricular (LV) pressure-volume loop and echocardiography evaluation under halogenate anesthesia. Effort testing with maximum O2 consumption (V̇o2 max) determination was performed 1 wk later. Obese ZSF1 showed lower effort tolerance and V̇o2 max along with higher resting EDP. Both Trendelenburg and phenylephrine increased EDP, whereas dobutamine decreased it. Significant correlations were found between EDP and 1) peak early filling Doppler velocity of transmitral flow (E) to corresponding myocardial tissue Doppler velocity (E′) ratio, 2) E to E-wave deceleration time (E/DT) ratio, and 3) left atrial area (LAA). Diagnostic efficiency of E/DT*LAA by receiver-operating characteristic curve analysis for elevation of EDP above a cut-off of 13 mmHg during hemodynamic stress was high (area under curve, AUC = 0.95) but not higher than that of E/E′ (AUC = 0.77, P = 0.15). Results in ZSF1 obese rats suggest that noninvasive echocardiography after hemodynamic stress induced by phenylephrine or Trendelenburg can enhance diagnosis of stable HFpEF and constitute an alternative to effort testing.

scholarly journals Wedge Pressure Rather Than Left Ventricular End-Diastolic Pressure Predicts Outcome in Heart Failure With Preserved Ejection Fraction

2017 ◽  
Vol 5 (11) ◽  
pp. 795-801 ◽  
Author(s):  
Julia Mascherbauer ◽  
Caroline Zotter-Tufaro ◽  
Franz Duca ◽  
Christina Binder ◽  
Matthias Koschutnik ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Diastolic Pressure ◽  
Left Ventricular ◽  
Preserved Ejection Fraction ◽  
Wedge Pressure

scholarly journals A study of association between heart failure with preserved ejection fraction with hypertension and diabetes mellitus

2021 ◽  
Vol 12 (12) ◽  
pp. 58-61
Author(s):  
Swapan Sarkar ◽  
Joydeep Biswas ◽  
Suprotim Ghosh
Keyword(s):  
Diabetes Mellitus ◽  
Risk Factors ◽  
Heart Failure ◽  
Ejection Fraction ◽  
Diastolic Pressure ◽  
Strong Association ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Preserved Ejection Fraction ◽  
Ventricular Ejection Fraction

Background: Heart failure is a common clinical entity which we come across in our daily practice and accounts for significant mortality and morbidity. The basic pathophysiology lies in the inability of the heart to pump adequate blood (output) to meet the demands of circulation/tissue or can do so only at the expense of elevated left ventricular filling pressure. Among various types of heart failure, heart failure with preserved ejection fraction (HFpEF) is still a poorly understood entity and several comorbidities such as hypertension, diabetes, coronary artery disease, obesity, and CKD are common association of HFpEF. Diabetes causes heart failure by increasing the risk of CAD and by direct injury to myocardium (cardiomyopathy). Hence, in this cross-sectional observational study, we assess the cardiovascular risk factors such as hypertension and diabetes mellitus in association with HFpEF. Aims and Objectives: This study aims to establish the hypothesis that hypertension and diabetes mellitus are associated with a predictor of HFpEF. Materials and Methods: Ninety patients were selected. NTproBNP, HbA1C, FBS, PPBS level, and blood pressure was measured and echocardiogram was performed to assess ratio of transmitral flow velocity and annular velocity (E/E’); left ventricular end-diastolic pressure; and left ventricular ejection fraction (LVEF). Results: The mean age was 64±7. Forty-two (46.67%) were men and 48 (53.33%) were female. Hypertension was present in 73 (81.11%) and diabetes in 44 (48.89%). E/E´, a parameter of LV diastolic function, showed positive correlation to both risk factors in study (r=0.653, p<0.001). Linear regression indicated that E/E’ (β-coefficient=0.845, p<0.001) was significantly associated with the presence of risk factors. Conclusion: The data show that the prevalence of HTN and DM is significantly higher in patients with HFpEF and establishes a strong association between duration of HTN and DM with symptomatic HFpEF.

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