scholarly journals Matrix Metalloproteinases and Tissue Inhibitors of Metalloproteinases in Extracellular Matrix Remodeling during Left Ventricular Diastolic Dysfunction and Heart Failure with Preserved Ejection Fraction: A Systematic Review and Meta-Analysis

2020 ◽  
Vol 21 (18) ◽  
pp. 6742 ◽  
Author(s):  
Merle M. Krebber ◽  
Christian G. M. van Dijk ◽  
Robin W. M. Vernooij ◽  
Maarten M. Brandt ◽  
Craig A. Emter ◽  
...  
Keyword(s):  
Heart Failure ◽  
Systematic Review ◽  
Extracellular Matrix ◽  
Ejection Fraction ◽  
Meta Analysis ◽  
Left Ventricular Diastolic Dysfunction ◽  
Left Ventricular ◽  
Tissue Inhibitors Of Metalloproteinases ◽  
Preserved Ejection Fraction ◽  
Ventricular Diastolic Dysfunction

Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) are pivotal regulators of extracellular matrix (ECM) composition and could, due to their dynamic activity, function as prognostic tools for fibrosis and cardiac function in left ventricular diastolic dysfunction (LVDD) and heart failure with preserved ejection fraction (HFpEF). We conducted a systematic review on experimental animal models of LVDD and HFpEF published in MEDLINE or Embase. Twenty-three studies were included with a total of 36 comparisons that reported established LVDD, quantification of cardiac fibrosis and cardiac MMP or TIMP expression or activity. LVDD/HFpEF models were divided based on underlying pathology: hemodynamic overload (17 comparisons), metabolic alteration (16 comparisons) or ageing (3 comparisons). Meta-analysis showed that echocardiographic parameters were not consistently altered in LVDD/HFpEF with invasive hemodynamic measurements better representing LVDD. Increased myocardial fibrotic area indicated comparable characteristics between hemodynamic and metabolic models. Regarding MMPs and TIMPs; MMP2 and MMP9 activity and protein and TIMP1 protein levels were mainly enhanced in hemodynamic models. In most cases only mRNA was assessed and there were no correlations between cardiac tissue and plasma levels. Female gender, a known risk factor for LVDD and HFpEF, was underrepresented. Novel studies should detail relevant model characteristics and focus on MMP and TIMP protein expression and activity to identify predictive circulating markers in cardiac ECM remodeling.

scholarly journals Effects of Exercise Training on Cardiac Function in Heart Failure with Preserved Ejection Fraction

2020 ◽  
Vol 6 ◽  
Author(s):  
Hidekatsu Fukuta
Keyword(s):  
Heart Failure ◽  
Exercise Training ◽  
Ejection Fraction ◽  
Meta Analysis ◽  
Left Ventricular Diastolic Function ◽  
Left Ventricular Diastolic Dysfunction ◽  
Left Ventricular ◽  
Exercise Intolerance ◽  
Preserved Ejection Fraction ◽  
Ventricular Diastolic Dysfunction

Nearly half of patients with heart failure in the community have heart failure with preserved ejection fraction (HFpEF). Patients with HFpEF are often elderly and their primary chronic symptom is severe exercise intolerance. Left ventricular diastolic dysfunction is associated with the pathophysiology of HFpEF and is an important contributor to exercise intolerance in HFpEF patients. The effects of exercise training on left ventricular diastolic function in HFpEF patients have been examined in several randomised clinical trials. Meta-analysis of the trials indicates that exercise training can provide clinically relevant improvements in exercise capacity without significant change in left ventricular structure or function in HFpEF patients. Further studies are necessary to elucidate the exact mechanisms of exercise intolerance in HFpEF patients and to develop recommendations regarding the most effective type, intensity, frequency, and duration of training in this group.

scholarly journals Opportunistic screening models for high-risk men and women to detect diastolic dysfunction and heart failure with preserved ejection fraction in the community

2018 ◽  
Vol 26 (6) ◽  
pp. 613-623 ◽  
Author(s):  
Aisha Gohar ◽  
Rogier F Kievit ◽  
Gideon B Valstar ◽  
Arno W Hoes ◽  
Evelien E Van Riet ◽  
...  
Keyword(s):  
Heart Failure ◽  
High Risk ◽  
Ejection Fraction ◽  
Diastolic Dysfunction ◽  
Left Ventricular Diastolic Dysfunction ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Preserved Ejection Fraction ◽  
Men And Women ◽  
Ventricular Diastolic Dysfunction

Background The prevalence of undetected left ventricular diastolic dysfunction is high, especially in the elderly with comorbidities. Left ventricular diastolic dysfunction is a prognostic indicator of heart failure, in particularly of heart failure with preserved ejection fraction and of future cardiovascular and all-cause mortality. Therefore we aimed to develop sex-specific diagnostic models to enable the early identification of men and women at high-risk of left ventricular diastolic dysfunction with or without symptoms of heart failure who require more aggressive preventative strategies. Design Individual patient data from four primary care heart failure-screening studies were analysed (1371 participants, excluding patients classified as heart failure and left ventricular ejection fraction <50%). Methods Eleven candidate predictors were entered into logistic regression models to be associated with the presence of left ventricular diastolic dysfunction/heart failure with preserved ejection fraction in men and women separately. Internal-external cross-validation was performed to develop and validate the models. Results Increased age and β-blocker therapy remained as predictors in both the models for men and women. The model for men additionally consisted of increased body mass index, moderate to severe shortness of breath, increased pulse pressure and history of ischaemic heart disease. The models performed moderately and similarly well in men (c-statistics range 0.60–0.75) and women (c-statistics range 0.51–0.76) and the performance improved significantly following the addition of N-terminal pro b-type natriuretic peptide (c-statistics range 0.61–0.80 in women and 0.68–0.80 in men). Conclusions We provide an easy-to-use screening tool for use in the community, which can improve the early detection of left ventricular diastolic dysfunction/heart failure with preserved ejection fraction in high-risk men and women and optimise tailoring of preventive interventions.

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.

scholarly journals UCP3 (Uncoupling Protein 3) Insufficiency Exacerbates Left Ventricular Diastolic Dysfunction During Angiotensin II‐Induced Hypertension

2021 ◽  
Vol 10 (18) ◽  
Author(s):  
Xu Chen ◽  
Sadia Ashraf ◽  
Nadia Ashraf ◽  
Romain Harmancey
Keyword(s):  
Heart Failure ◽  
Angiotensin Ii ◽  
Ejection Fraction ◽  
Diastolic Dysfunction ◽  
Uncoupling Protein ◽  
Left Ventricular Diastolic Dysfunction ◽  
Left Ventricular ◽  
Preserved Ejection Fraction ◽  
Uncoupling Protein 3 ◽  
Ventricular Diastolic Dysfunction

Background Left ventricular diastolic dysfunction, an early stage in the pathogenesis of heart failure with preserved ejection fraction, is exacerbated by joint exposure to hypertension and obesity; however, the molecular mechanisms involved remain uncertain. The mitochondrial UCP3 (uncoupling protein 3) is downregulated in the heart with obesity. Here, we used a rat model of UCP3 haploinsufficiency (ucp3 +/‐ ) to test the hypothesis that decreased UCP3 promotes left ventricular diastolic dysfunction during hypertension. Methods and Results Ucp3 +/‐ rats and ucp3 +/+ littermates fed a high‐salt diet (HS; 2% NaCl) and treated with angiotensin II (190 ng/kg per min for 28 days) experienced a similar rise in blood pressure (158±4 versus 155±7 mm Hg). However, UCP3 insufficiency worsened diastolic dysfunction according to echocardiographic assessment of left ventricular filling pressures (E/e’; 18.8±1.0 versus 14.9±0.6; P <0.05) and the isovolumic relaxation time (24.7±0.6 versus 21.3±0.5 ms; P <0.05), as well as invasive monitoring of the diastolic time constant (Tau; 15.5±0.8 versus 12.7±0.2 ms; P <0.05). Exercise tolerance on a treadmill also decreased for HS/angiotensin II‐treated ucp3 +/‐ rats. Histological and molecular analyses further revealed that UCP3 insufficiency accelerated left ventricular concentric remodeling, detrimental interstitial matrix remodeling, and fetal gene reprogramming during hypertension. Moreover, UCP3 insufficiency increased oxidative stress and led to greater impairment of protein kinase G signaling. Conclusions Our findings identified UCP3 insufficiency as a cause for increased incidence of left ventricular diastolic dysfunction during hypertension. The results add further support to the use of antioxidants targeting mitochondrial reactive oxygen species as an adjuvant therapy for preventing heart failure with preserved ejection fraction in individuals with obesity.

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