scholarly journals Poorer Exercise Accommodation of Regional Systolic Myocardial Motion after Spironolactone Treatment in Heart Failure Patients with Preserved Ejection Fraction and Ventricular Dyssynchrony

2021 ◽  
Vol 10 (17) ◽  
pp. 3827
Author(s):  
Chih-Chieh Yu ◽  
Fu-Chun Chiu ◽  
Chia-Ti Tsai ◽  
Yi-Chih Wang ◽  
Ling-Ping Lai ◽  
...  

Patients with heart failure and preserved ejection fraction (HFpEF) are known to have reduced systolic myocardial velocity (Sm) with impaired accommodation to exercise. We tested the impact of an aldosterone antagonist on Sm at rest and post-exercise. Forty-nine HFpEF patients (65 ± 11 years, 24 male) with HF signs/symptoms, mitral E/Ea (annular early diastolic velocity) > 8, and left ventricular (LV) EF > 50% were randomized to spironolactone (25 mg/day, 25 patients) or the Control. At baseline and 6 months, we analyzed Sm of basal LV segments at rest and after a 6 min treadmill exercise. At 6 months, post-exercise mean Sm in the spironolactone group became greater than that in the Control (9.2 ± 1.6 vs. 8.3 ± 1.0 cm/s, p = 0.021), mainly due to the increment of post-exercise % increase of lateral Sm (44 ± 30 vs. 30 ± 19% at baseline, p = 0.045). Further analyses showed the presence of systolic dyssynchrony (standard deviation of electromechanical delay of 6-basal LV segments > 35 ms) was independently associated with a poorer response to spironolactone, defined as a post-exercise % increase of lateral Sm < 50% (OR = 2.7, 95% CI = 1.8–4.2) and the increment of Ea < 1.5 cm/s (OR = 1.5, 95% CI = 1.1–2.3). Spironolactone could improve exercise accommodation of regional systolic myocardial velocity for HFpEF patients. However, its benefits could be decreased in those with ventricular dyssynchrony. This suggested possible therapeutic impacts from underlying heterogeneity within HFpEF patients.

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Anett Jannasch ◽  
Antje Schauer ◽  
Virginia Kirchhoff ◽  
Runa Draskowsi ◽  
Claudia Dittfeld ◽  
...  

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.


2013 ◽  
Vol 35 (1) ◽  
pp. 42-47 ◽  
Author(s):  
A. B. S. Santos ◽  
E. Kraigher-Krainer ◽  
N. Bello ◽  
B. Claggett ◽  
M. R. Zile ◽  
...  

2020 ◽  
Vol 21 (Supplement_1) ◽  
Author(s):  
M Przewlocka-Kosmala ◽  
E Jasic-Szpak ◽  
E A Jankowska ◽  
P Ponikowski ◽  
W Kosmala

Abstract The intracellular iron depletion has been recognized to contribute to the dysregulation of cell energetics. The soluble transferrin receptor (sTfR) is regarded as a marker of cellular iron balance, and its elevated level reflects an insufficient iron delivery to target tissues. Despite the strong pathophysiological link, there is a scarcity of data on the impact of intracellular iron status on myocardial performance. Aim To investigate the association between the intracellular iron status, as assessed by sTfR, and left ventricular (LV) function in a well-characterized population with heart failure and preserved ejection fraction (HFpEF). Methods A complete echocardiogram including evaluation of LV global longitudinal deformation by speckle tracking (GLS) was performed at rest and immediately post-exercise in 83 pts (age 66 ± 8 yrs) with symptomatic HFpEF. Results Pts with the highest sTfR concentrations (from the 3rd sTfR tertile) demonstrated significantly lower exertional GLS than their peers from the other 2 tertiles and lower resting GLS vs. the 2nd tertile (Table). Exercise GLS was inversely correlated with sTfR (r=-0.27, p = 0.01), and this association remained significant after adjustment for age, sex, BMI, LV mass, exercise blood pressure, hemoglobin and serum galectin-3 – a marker of fibrosis (beta=-0.24, p = 0.04). Conclusions In HFpEF, higher sTfR reflecting a decreased global intracellular iron content is independently associated with reduced LV longitudinal contractility response to exertion. This might represent another mechanism of exercise intolerance and should be considered in management strategies in this condition. Abstract P935 Figure.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
F.H Verbrugge ◽  
Y.N.V Reddy ◽  
S Kapa ◽  
B.A Borlaug

Abstract Background Diastolic reserve decreases with aging. A recently developed artificial intelligence (AI) algorithm can predict age based on 12-lead electrocardiogram (ECG) analysis. Purpose This study aims to use a validated AI algorithm to assess cardiac senescence and investigate the impact of obesity on cardiac aging in heart failure with preserved ejection fraction (HFpEF). Methods This retrospective cohort study includes 403 patients with HFpEF, admitted for treatment with intravenous diuretics. ECG age was assessed by a convolutional neural network as previously validated. Patients were stratified according to the presence of obesity (body mass index &gt;30 kg/m2) and ECG age was compared between groups. The relationship between ECG versus calendar age and structural/functional alterations on echocardiography, as well as the risk of atrial fibrillation (AF) development, was evaluated. Results In 253 (63%) obese patients with HFpEF, calendar age was 8 years younger compared with their non-obese counterparts, but ECG age was only 3 years younger. ECG minus calendar age was higher in obese patients (P-value &lt;0.001; figure) and correlated moderately strong with weight, fat free, and fat mass (r=0.35–0.41; P-value &lt;0.001). Older ECG age was correlated with worse diastolic function, but not with left ventricular afterload (table). Calendar age correlated less strongly with diastolic dysfunction (table). ECG age did predict AF development, independently of calendar age, gender, and presence of obesity [HR (95% CI) = 1.31 (1.06–1.63) per 5-year; P-value=0.015]. Conclusions Obesity accelerates cardiac senescence in HFpEF as reflected by more pronounced diastolic dysfunction and a higher AF risk, which was identified from ECG analysis by a validated AI algorithm. Figure 1 Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): Belgian American Educational Foundation (B.A.E.F.); Special Research Fund (BOF) of Hasselt University (Hasselt, Belgium).


2020 ◽  
Vol 34 (2) ◽  
pp. 250-256 ◽  
Author(s):  
Midoriko Higashi ◽  
Kenji Shigematsu ◽  
Kenji Tominaga ◽  
Kazuya Murayama ◽  
Daisuke Seo ◽  
...  

Abstract Purpose Left ventricular diastolic dysfunction is an independent risk factor for adverse cardiovascular morbidities and mortalities in cardiovascular and high-risk surgical patients. However, there were only a few investigations among intermediate-risk surgical patients. This study aimed to investigate postoperative heart failure (HF) in intermediate-risk surgical patients who had preoperative diastolic dysfunction with preserved ejection fraction (EF). Methods Consecutive patients underwent intermediate-risk surgery between January 2016 and December 2018 were retrospectively evaluated. Patients with preserved EF were divided into three groups using one of the parameters of diastolic function: the ratio of early diastolic filling velocity to the peak diastolic velocity of mitral medial annulus (E/e’) ≥ 15, E/e’ between 8 and 15, and E/e’ < 8. Postoperative HF was defined as clinical symptoms and radiological evidence and low SpO2 less than 93%. The primary outcome was the incidence of postoperative HF and its relation to preoperative E/e’. Chi-squared test, unpaired t test with Welch’s correction, and multivariate logistic regression were used for analysis. Results In total, 965 patients were included in the final analysis. Postoperative HF developed in 36/965 (3.7%) patients with preserved EF. The incidence of postoperative HF was stratified according to the E/e’, and the rates of HF occurrence in patients with E/e’ < 8, 8–15, and ≥ 15 were 1.8%, 2.7%, and 15%, respectively (P < 0.01). Conclusion Preoperative elevated E/e’ (≥ 15) was associated with the development of postoperative HF in intermediate-risk surgical patients with preserved EF.


Circulation ◽  
2018 ◽  
Vol 138 (Suppl_1) ◽  
Author(s):  
Keishi Moriwaki ◽  
Naoki Fujimoto ◽  
So Miyahara ◽  
Shusuke Fukuoka ◽  
Masaki Ishiyama ◽  
...  

Introduction: Isometric handgrip (IHG) training at 30% maximal voluntary contraction (MVC) lowers blood pressure (BP) in patients with hypertension and healthy individuals. However, impacts of IHG and post-exercise circulatory arrest (PECA), which isolates the metaboreflex control, on left ventricular (LV) function and hemodynamics have been unclear in patients with heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF). Methods: Sixteen patients with HF (age 63±13 years, 5M:11F, 10HFpEF:6HFrEF) underwent invasive LV pressure-volume assessments using conductance catheter with microtip-manometer during 3min of IHG exercise at 30% MVC, followed by 3 min of PECA. Impacts of IHG and PECA on LV function and hemodynamics were evaluated and compared between HFpEF and HFrEF. Results: During 3 min of IHG at 30% MCV, heart rate increased by 10±8 bpm in HFpEF and by 14±6 bpm in HFrEF. IHG elevated LV end-systolic BP in both HFpEF (134±21 vs. 158±30 mmHg, p<0.01) and HFrEF (119±30 vs. 142±31 mmHg, p<0.01) with no change in stroke volume. There was a trend towards an increase in LV end-diastolic pressure in both groups (HFpEF:14±5 vs. 19±10 mmHg, HFrEF: 15±12 vs. 23±11 mmHg). Time constant of LV relaxation was unchanged by 3 min of IHG in HFpEF (52±14 vs. 54±15 ms), while it was prolonged in HFrEF (48±7 vs. 60±9 ms, p<0.01, groupхtime interaction effect p=0.08). During PECA, LV end-systolic BP decreased in both groups and was maintained higher than baseline throughout PECA only in HFpEF. Conclusions: Although IHG exercise at 30% MVC for 3 min would elevate LV end-systolic and end-diastolic pressures, this IHG exercise has no detrimental effect on LV systolic and diastolic function, especially in HFpEF patients. Chronic effect of IHG training on BP and hemodynamics will need to be evaluated in HFpEF patients who often suffer from arterial hypertension.


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