RVOT-VTI/PASP: A NOVEL NON-INVASIVE METRIC OF PULMONARY ARTERIAL COMPLIANCE AND DIASTOLIC PRESSURE GRADIENT STATUS IN HEART FAILURE WITH PRESERVED EJECTION FRACTION

Introduction: Diabetes is observed in about third of patients with heart failure with preserved ejection fraction (HFpEF), and it is not well elucidated how it would affect the clinical conditions of HFpEF. We investigated the physical and echocardiographic characteristics of diabetes patients in a large-scale, registration study of HFpEF. Methods: We analyzed clinical and echocardiography data obtained at admission and just before hospital discharge in the PURSUIT-HFpEF (Prospective, Multicenter, Observational Study of Patients with Heart Failure with Preserved Ejection Fraction), which is a multicenter registration study of patients who were hospitalized for HFpEF. Results: We enrolled 862 patients who were hospitalized for HFpEF between June, 2016 and December, 2019 (Age 81±9 years, male gender 44.5%) for the present study. Diabetes was observed in 287 patients (33.3%), and their age was higher (82±8 years vs. 80±9 years, p=0.003) and body mass index before discharge was larger (23.2±4.7 kg/m2 vs. 21.1±4.6 kg/m2, p<0.0001) than those without diabetes. Diabetic patients had higher body weight at admission (63.2±14.9 kg vs. 55.9±13.4 kg, p<0.0001) and before discharge (56.8±13.3 vs. 50.7±12.1 kg, p<0.0001) than non-diabetic patients. Reduction of body weight during hospital stay was higher in diabetic patients (6.4±4.5 kg) than in non-diabetic patients (5.2±4.0 kg) even after correction of body weight discharge or estimated GFR (p<0.001 by ANCOVA). Body weight reduction was significantly associated with HbA1c (p=0.01). There was no difference in use of intravenous diuretics (69.3% vs. 66.6%, p=0.44) and in hospital stay (21.4±15.3 days vs. 19.9±13.7 days, p=0.14) between diabetic- and non-diabetic patients. Whereas no differences were observed in echocardiographic parameters at admission and before discharge between two arms, the diabetic arm showed significantly higher reduction in septal E/e’ ratio during hospital stay (19.0±8.7 to 17.1±7.6) than non-diabetic arm (16.6±8.3 to 16.4±8.2)(p=0.01 by repeated measure ANOVA). Conclusions: The present study implied that diabetic patients with HFpEF have more fluid retention before hospitalization than non-diabetic ones, which could affect the changes in diastolic pressure.

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

Journal of Applied Physiology ◽

10.1152/japplphysiol.00718.2017 ◽

2018 ◽

Vol 124 (1) ◽

pp. 76-82 ◽

Cited By ~ 3

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.

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Abstract 19944: Targeted Therapy of Pulmonary Hypertension in Patients With Heart Failure and Preserved Ejection Fraction: Safety and Efficacy in Comparison to IPAH in Compera

Circulation ◽

10.1161/circ.132.suppl_3.19944 ◽

2015 ◽

Vol 132 (suppl_3) ◽

Author(s):

Stephan Rosenkranz ◽

Marius M Hoeper ◽

Doerte Huscher ◽

David Pittrow ◽

Christian F Opitz

Keyword(s):

Risk Factors ◽

Heart Failure ◽

Pulmonary Hypertension ◽

Ejection Fraction ◽

Preserved Ejection Fraction ◽

Evidence Based Treatment ◽

Patients With Heart Failure ◽

Venous Oxygen Saturation ◽

Initial Ph ◽

Pulmonary Arterial

Background: While targeted therapies are available for idiopathic pulmonary arterial hypertension (IPAH), evidence based treatment recommendations for pulmonary hypertension (PH) associated with heart failure and preserved ejection fraction (HFpEF) are lacking. Methods and Results: Out of 5,935 patients in the prospective COMPERA registry, we analyzed patients with “typical” IPAH (n=421, ≤2 of the following risk factors: BMI >30 kg/m2, hypertension, CAD, diabetes and atrial fibrillation at the time of diagnosis), “atypical” IPAH (n=139, >2 risk factors) or PH-HFpEF (n=226) who received targeted PH therapies. Patients with PH-HFpEF, when compared to “typical” and “atypical” IPAH were older (73±8 vs. 62±17 and 71±9 years), had a higher BMI (30 vs. 26 and 32 kg/m2), and more comorbidities (98% vs. 73% and 100%, all p<0.001), respectively. However, mean PAP (46±9 vs. 47±13 and 44±11 mmHg), cardiac index (2.2±0.7 vs. 2,3±0,8 and 2,2±0,8 l/min), and mixed venous oxygen saturation (62±7 vs. 62±10 and 63±9%, all ns) were almost identical. As compared to “typical” and “atypical” IPAH, PH-HFpEF patients had a higher PAWP (20±4 vs. 9±3 and 10±4 mmHg), resulting in a lower calculated PVR (559±270 vs. 861±477 and 784±844 dyn.s.cm-5). Survival at 1, 2 and 3 years post diagnosis was not different between groups. PDE-5 inhibitors were the most common form of initial PH treatment in PH-HFpEF (94%), and combination therapy was less common compared to “typical” or “atypical” IPAH at 1 year (7% vs. 44% and 26%). All 3 groups responded to targeted PH therapies at 12 months, while treatment effects were less pronounced in PH-HFpEF: Compared to baseline, the median increase of the 6MWD at 1 year was 29, 50, and 60 m, respectively. Treatment discontinuations occurred more frequently in patients with PH-HFpEF than in IPAH, either because of side effects or lack of improvement. Conclusions: Despite almost identical alterations of pulmonary artery pressure and cardiac output, patients with PH-HFpEF differed with respect to age, comorbidities and certain hemodynamic features when compared to “typical” or “atypical” IPAH. All groups responded to targeted PH therapy, however tolerability and efficacy of PH drugs were reduced in patients with PH-HFpEF while survival was not different.

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Abstract 420: Characterization of Dahl Salt-Sensitive Rat Model for Heart Failure with Preserved Ejection Fraction Research: Defining Diagnostic Criteria

Hypertension ◽

10.1161/hyp.64.suppl_1.420 ◽

2014 ◽

Vol 64 (suppl_1) ◽

Author(s):

Natale Rolim ◽

Jose B Moreira ◽

Alessandra Medeiros ◽

Marcia Alves ◽

Xiaojuan Yang ◽

...

Keyword(s):

Heart Failure ◽

Ejection Fraction ◽

Diagnostic Criteria ◽

Diastolic Pressure ◽

Control Group ◽

Chronic Hypertension ◽

Preserved Ejection Fraction ◽

Cross Sectional ◽

Criteria For Diagnosis ◽

Novel Therapeutic Strategies

Heart failure with preserved ejection fraction (HFpEF) is a condition that accounts for approximately 50 % of heart failure cases with the prevalence increased with advancing age. As of now, no effective treatment is available for HFpEF, which calls for continued efforts towards novel therapies. Dahl salt-sensitive (Dahl SS) rats have recently been reported as an experimental model of HFpEF, although a specific diagnostic criteria for HFpEF is still unclear in rodents. We aimed to provide clear criteria to identify HFpEF in Dahl SS rats. After a follow-up of 28 weeks, adult female Dahl SS rats receiving high salt (HS, 8 % NaCl) diet developed chronic hypertension (209 ± 80 vs. 147 ± 55 mm Hg; P <0.05 vs. low salt-fed control group (LS, 0.3 % NaCl) with consistent left ventricle (LV) remodeling compared to LS rats (LV hypertrophy index: 2.62 ± 0.07 vs. 1.79 ± 0.03 mg/mm, and cardiomyocyte cross-sectional area: 497 ± 38.9 vs. 290 ± 8.15 μm 2 , respectively; P < 0.05) and EF > 50 % (67.7 ± 1.5 %). Evidence that HS rats have developed HFpEF was observed only in rats with left atrial dimension (LAD)/body weight (BW), E/A, and E/E’ ratios above the 75 th percentile of the LS group (17.50 mm/kg, 1.53, and 14.25, respectively). In addition, HS rats diagnosed with HFpEF had increased LV end-diastolic pressure and plasma NT-proBNP compared to LS rats (12.8 ± 3.4 vs. 5.8 ± 0.8 mm Hg, and 78.7 ± 18.0 vs. 17.7 ± 3.5 pg/mL, respectively; P < 0.05), while no significant changes in LAD/BW, E/A, E/E’, and plasma NT-proBNP were demonstrated in HS rats not matching the suggested criteria for HFpEF. Distance run was not different between HS and LS groups. Survival rate was 39.9 % in HS compared to 94.7 % in LS rats ( P = 0.0001), with stroke as the main cause of death (69.6 % incidence in HS rats). These results provide the first clear criteria for diagnosis of HFpEF in Dahl SS rats. Our findings have important implications for future preclinical studies aiming to develop novel therapeutic strategies targeting diastolic dysfunction in HFpEF.

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

Circulation ◽

10.1161/circ.142.suppl_3.15172 ◽

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.

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H2FPEF score predicts 1-year rehospitalisation of patients with heart failure with preserved ejection fraction

Postgraduate Medical Journal ◽

10.1136/postgradmedj-2019-137434 ◽

2020 ◽

pp. postgradmedj-2019-137434

Author(s):

Yifei Tao ◽

Wenjing Wang ◽

Jing Zhu ◽

Tao You ◽

Yi Li ◽

...

Keyword(s):

Heart Failure ◽

Regression Analysis ◽

Ejection Fraction ◽

Cox Regression ◽

Area Under The Curve ◽

Support Vector ◽

Preserved Ejection Fraction ◽

Cox Regression Analysis ◽

Non Invasive ◽

Patients With Heart Failure

BackgroundHeart failure with preserved ejection fraction (HFpEF) has received widespread attention in recent years. There is currently a lack of valuable predictors for the prognosis of this disease. Here, we aimed to identify a non-invasive scoring system that can effectively predict 1-year rehospitalisation for patients with HFpEF.MethodsWe included 151 consecutive patients with HFpEF in a prospective cohort study and investigated the association between H2FPEF score and 1-year readmission for heart failure using multivariate Cox regression analysis.ResultsOur findings indicated that obesity, age >70 years, treatment with ≥2 antihypertensives, echocardiographic E/e’ ratio >9 and pulmonary artery pressure >35 mm Hg were independent predictors of 1-year readmission. Three models (support vector machine, decision tree in R and Cox regression analysis) proved that H2FPEF score could effectively predict 1-year readmission for patients with HFpEF (area under the curve, 0.910, 0.899 and 0.771, respectively; p<0.001).ConclusionOur study demonstrates that the H2FPEF score has excellent predictive value for 1-year rehospitalisation of patients with HFpEF.

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