scholarly journals Myofilament Phosphorylation in Stem Cell Treated Diastolic Heart Failure

2021 ◽  
Author(s):  
Daniel Soetkamp ◽  
Romain Gallet ◽  
Sarah J Parker ◽  
Ronald Holewinski ◽  
Vidya Venkatraman ◽  
...  
Keyword(s):  
Heart Failure ◽  
Diastolic Dysfunction ◽  
Diastolic Heart Failure ◽  
Medical Intervention ◽  
Left Ventricular ◽  
High Salt Diet ◽  
Salt Diet ◽  
Protein Residues ◽  
Ventricular Tissue ◽  
Pkc Isoforms

Rationale: Phosphorylation of sarcomeric proteins has been implicated in heart failure with preserved ejection fraction (HFpEF); such changes may contribute to diastolic dysfunction by altering contractility, cardiac stiffness, Ca 2+ -sensitivity and mechanosensing. Treatment with cardiosphere-derived cells (CDCs) restores normal diastolic function, attenuates fibrosis and inflammation, and improves survival in a rat HFpEF model. Objective: Phosphorylation changes that underlie HFpEF and those reversed by CDC therapy, with a focus on the sarcomeric subproteome were analyzed. Methods and Results: Dahl salt-sensitive rats fed a high-salt diet, with echocardiographically-verified diastolic dysfunction, were randomly assigned to either intracoronary CDCs or placebo. Dahl salt-sensitive rats receiving low salt diet served as controls. Protein, and phosphorylated Ser, Thr and Tyr residues from left ventricular tissue, were quantified by mass spectrometry. HFpEF hearts exhibited extensive hyperphosphorylation with 98% of the 529 significantly changed phospho-sites increased compared to control. Of those 39% were located within the sarcomeric subproteome, with a large group of proteins located or associated with the Z-disk. CDC treatment partially reverted the hyperphosphorylation, with 85% of the significantly altered 76 residues hypophosphorylated. Bioinformatic upstream analysis of the differentially phosphorylated protein residues revealed PKC as the dominant putative regulatory kinase. PKC isoform analysis indicated increases in PKC α, β and δ concentration, whereas CDC treatment led to a reversion of PKCβ. Use of PKC isoform specific inhibition and overexpression of various PKC isoforms strongly suggests PKCβ is the dominant kinase involved in hyperphosphorylation in HFpEF and is altered with CDC treatment. Conclusions: Increased protein phosphorylation at the Z-disk is associated with diastolic dysfunction, with PKC isoforms driving most quantified phosphorylation changes. Because CDCs reverse the key abnormalities in HFpEF and selectively reverse PKCβ upregulation, PKCβ merits being classified as a potential therapeutic target in HFpEF, a disease notoriously refractory to medical intervention,

Investigation of the Relationship Between Color M-Mode Early Diastolic Propagation Velocity and Left Ventricular Adverse Pressure Gradients

2010 ◽  
Author(s):  
Kelley C. Stewart ◽  
Rahul Kumar ◽  
John J. Charonko ◽  
Pavlos P. Vlachos ◽  
William C. Little
Keyword(s):  
Heart Failure ◽  
Diastolic Dysfunction ◽  
Diastolic Heart Failure ◽  
Diagnostic Techniques ◽  
Left Ventricular Diastolic Dysfunction ◽  
Left Ventricular ◽  
Pressure Gradients ◽  
Compensatory Mechanisms ◽  
Ventricular Diastolic Dysfunction ◽  
The Relationship

Left ventricular diastolic dysfunction (LVDD) and diastolic heart failure are conditions that affect the filling dynamics of the heart and affect 36% of patients diagnosed with congestive heart failure [1]. Although this condition is very prevalent, it currently remains difficult to diagnose due to inherent atrio-ventricular compensatory mechanisms including increased heart rate, increased left ventricular (LV) contractility, and increased left atrial pressure (LA). A greater comprehension of the governing flow physics in the left ventricle throughout the introduction of the heart’s compensatory mechanisms has great potential to substantially increase the understanding of the progression of diastolic dysfunction and in turn advance the diagnostic techniques.

Role of Diastole in Left Ventricular Function, II: Diagnosis and Treatment

2004 ◽  
Vol 13 (6) ◽  
pp. 453-466 ◽  
Author(s):  
Shannan K. Hamlin ◽  
Penelope S. Villars ◽  
Joseph T. Kanusky ◽  
Andrew D. Shaw
Keyword(s):  
Heart Failure ◽  
Diastolic Dysfunction ◽  
Left Atrial ◽  
Diastolic Heart Failure ◽  
Systolic Heart Failure ◽  
Clinical Signs ◽  
Left Ventricular ◽  
Exercise Intolerance ◽  
Radiographic Findings ◽  
Ventricular Compliance

Left ventricular diastolic dysfunction plays an important role in congestive heart failure. Although once thought to be lower, the mortality of diastolic heart failure may be as high as that of systolic heart failure. Diastolic heart failure is a clinical syndrome characterized by signs and symptoms of heart failure with preserved ejection fraction (0.50) and abnormal diastolic function. One of the earliest indications of diastolic heart failure is exercise intolerance followed by fatigue and, possibly, chest pain. Other clinical signs may include distended neck veins, atrial arrhythmias, and the presence of third and fourth heart sounds. Diastolic dysfunction is difficult to differentiate from systolic dysfunction on the basis of history, physical examination, and electrocardiographic and chest radiographic findings. Therefore, objective diagnostic testing with cardiac catheterization, Doppler echocardiography, and possibly measurement of serum levels of B-type natriuretic peptide is often required. Three stages of diastolic dysfunction are recognized. Stage I is characterized by reduced left ventricular filling in early diastole with normal left ventricular and left atrial pressures and normal compliance. Stage II or pseudonormalization is characterized by a normal Doppler echocardiographic transmitral flow pattern because of an opposing increase in left atrial pressures. This normalization pattern is a concern because marked diastolic dysfunction can easily be missed. Stage III, the final, most severe stage, is characterized by severe restrictive diastolic filling with a marked decrease in left ventricular compliance. Pharmacological therapy is tailored to the cause and type of diastolic dysfunction.

Link between diabetes and diastolic dysfunction and the diagnostic role of echocardiography

2009 ◽  
Vol 150 (45) ◽  
pp. 2060-2067 ◽  
Author(s):  
András Nagy ◽  
Zsuzsanna Cserép
Keyword(s):  
Heart Failure ◽  
Diastolic Dysfunction ◽  
Systolic Function ◽  
Diastolic Heart Failure ◽  
Systolic Dysfunction ◽  
Mitral Annulus ◽  
Left Ventricular ◽  
Diabetic Patients ◽  
Doppler Study

Diabetes mellitus, a disease that has been reaching epidemic proportions, is an important risk factor to the development of cardiovascular complication. The left ventricular diastolic dysfunction represents the earliest pre-clinical manifestation of diabetic cardiomyopathy, preceding systolic dysfunction and being able to evolve to symptomatic heart failure. In early stages, these changes appear reversible with tight metabolic control, but as pathologic processes become organized, the changes are irreversible and contribute to an excess risk of heart failure among diabetic patients. Doppler echocardiography provides reliable data in the stages of diastolic function, as well as for systolic function. Combination of pulsed tissue Doppler study of mitral annulus with transmitral inflow may be clinically valuable for obtaining information about left ventricular filling pressure and unmasking Doppler inflow pseudonormal pattern, a hinge point for the progression toward advanced heart failure. Subsequently we give an overview about diabetes and its complications, their clinical relevance and the role of echocardiography in detection of diastolic heart failure in diabetes.

Abstract P490: Vascular Rarefaction And Decreased Angiogenic Potential In The Development Of Left Ventricular Diastolic Dysfunction In Heart Failure With Preserved Ejection Fraction

2021 ◽  
Vol 129 (Suppl_1) ◽  
Author(s):  
Katie Anne Fopiano ◽  
Yanna Tian ◽  
Vadym Buncha ◽  
Liwei Lang ◽  
Zsolt Bagi
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Diastolic Dysfunction ◽  
Rat Model ◽  
Ex Vivo ◽  
Diastolic Heart Failure ◽  
Left Ventricular ◽  
Coronary Microvascular Dysfunction ◽  
Preserved Ejection Fraction ◽  
Angiogenic Potential

Coronary microvascular dysfunction (CMD) develops in patients with heart failure with preserved ejection fraction (HFpEF, also known as diastolic heart failure), but the nature of the underlying pathomechanisms behind this prevalent disease remain poorly understood. The hypothesis tested was that coronary microvascular rarefaction contributes to left ventricle (LV) diastolic function in HFpEF. The obese ZSF1 rat model of human HFpEF was employed and using transthoracic echocardiography it was found that 18-week-old male obese ZSF1 rats exhibited a significantly reduced E/A ratio (E=early, A=late mitral inflow peak velocities) and increased DT (E wave deceleration time) with no change in ejection fraction, indicating diastolic dysfunction. Coronary arteriolar and capillary trees were labeled using Tomato Lectin (Lycopersicon esculentum) DyLight®594 and were imaged by fluorescent confocal microscopy to generate image stacks for 3D reconstruction. Unbiased automated tracing of the microvasculature was done using VesselLucida360 software (MBF) followed by a morphometric analysis (VesselLucida Explorer). It was found that total vessel length and the number of vessel’s branching nodes were reduced in the obese ZSF1 rats, whereas the total vessel’s volumes remained consistent, when compared to the lean ZSF1 controls. These changes in the microvasculature were accompanied by decreased angiogenesis in the coronary arteries in the obese ZSF1 rats when compared to the lean ZSF1 rats using an ex vivo endothelial sprouting assay. From these results, it was concluded that vascular rarefaction and decreased angiogenesis both play a role in the development of LV diastolic dysfunction in the obese ZSF1 rat model of human HFpEF.

Evaluation of Diastolic Dysfunction Using Cardiac Magnetic Resonance Imaging

2010 ◽  
Vol 6 (1) ◽  
pp. 21 ◽  
Author(s):  
Tarun Pandey ◽  
Kedar Jambhekar ◽  
◽  
Keyword(s):  
Heart Failure ◽  
Cardiac Magnetic Resonance ◽  
Magnetic Resonance ◽  
Diastolic Dysfunction ◽  
Systolic Function ◽  
Diastolic Heart Failure ◽  
Pulmonary Veins ◽  
Left Ventricular ◽  
Function Evaluation ◽  
Lv Function

Left ventricular (LV) diastolic dysfunction and diastolic heart failure (DHF) account for approximately 40–50% of all patients with congestive heart failure (CHF). Diastolic dysfunction can be evaluated directly by invasive cardiac catheterisation techniques or non-invasively by transthoracic echocardiography (TTE) or cardiac magnetic resonance (CMR) imaging. Due to its high spatial and temporal resolution, CMR is the accepted gold standard for evaluating ventricular systolic function. Using the cine-phase contrast technique, CMR can interrogate inflow through the mitral valve and pulmonary veins towards evaluation of diastolic dysfunction and has shown good correlation with TTE. Additionally, CMR can evaluate direct myocardial diastolic parameters that have no echo correlate, such as diastolic torsion rate. As CMR has the ability to characterise a range of diastolic impairments, it will likely become an important diagnostic test in the future, capable of comprehensive LV function evaluation. In this article, we focus on LV diastology, and review CMR methodology and parameters for the diagnosis of diastolic dysfunction.

Heart failure with preserved ejection fraction (diastolic heart failure)

2012 ◽  
Vol 153 (51) ◽  
pp. 2030-2040 ◽  
Author(s):  
István Czuriga ◽  
Attila Borbély ◽  
Dániel Czuriga ◽  
Zoltán Papp ◽  
István Édes
Keyword(s):  
Heart Failure ◽  
Heart Rate ◽  
Ejection Fraction ◽  
Diastolic Dysfunction ◽  
Diastolic Heart Failure ◽  
Left Ventricular ◽  
Preserved Ejection Fraction ◽  
Normal Left Ventricular ◽  
Left Ventricular Dimensions ◽  
Ventricular Dimensions

Diastolic heart failure, which is also called as heart failure with preserved ejection fraction, is a clinical syndrome in which patients have signs and symptoms of heart failure, normal or near normal left ventricular ejection fraction (≥50%) and evidence of diastolic dysfunction. Recent epidemiological studies have demonstrated that more than half of all heart failure patients have diastolic heart failure. The syndrome is more common in women than in men and the prevalence increases with age. Patients with diastolic heart failure form a fairly heterogeneous group with complex pathophysiologic mechanisms. The disease is often in association with other comorbidities, such as hypertension, diabetes mellitus or obesity. The diagnosis of diastolic heart failure is best achieved by two-dimensional and Doppler echocardiography, which can detect abnormal myocardial relaxation, decreased compliance and increased filling pressure in the setting of normal left ventricular dimensions and preserved ejection fraction. Unlike heart failure with reduced ejection fraction, there is no such an evidence-based treatment for heart failure with preserved ejection fraction, which would improve clinical outcomes. Thus, pharmacological therapy of diastolic heart failure is based mainly on empiric data, and aims to the normalization of blood pressure, reduction of left ventricular dimensions and increased heart rate, maintenance of normal atrial contraction and treatment of symptoms caused by congestion. Beneficial effects of angiotensin-converting enzyme inhibitors and angiotensin-receptor blockers may be utilized in patients with diastolic dysfunction, especially in those with hypertension. Beta-blockers appear to be useful in lowering heart rate and thereby prolonging left ventricular diastolic filling time, while diuretic therapy is the mainstay of treatment for preventing pulmonary congestion. Nonetheless, treatment of the underlying disease is also an important therapeutic approach. This review summarizes the state of current knowledge with regard to diastolic heart failure. Orv. Hetil., 2012, 153, 2030–2040.

scholarly journals Predictive Modeling of Secondary Pulmonary Hypertension in Left Ventricular Diastolic Dysfunction

2021 ◽  
Vol 12 ◽  
Author(s):  
Karlyn K. Harrod ◽  
Jeffrey L. Rogers ◽  
Jeffrey A. Feinstein ◽  
Alison L. Marsden ◽  
Daniele E. Schiavazzi
Keyword(s):  
Heart Failure ◽  
Pulmonary Hypertension ◽  
Right Ventricular ◽  
Diastolic Dysfunction ◽  
Diastolic Heart Failure ◽  
Circulation Model ◽  
Left Ventricular ◽  
Data Availability ◽  
Model Parameters ◽  
Ventricular Afterload

Diastolic dysfunction is a common pathology occurring in about one third of patients affected by heart failure. This condition may not be associated with a marked decrease in cardiac output or systemic pressure and therefore is more difficult to diagnose than its systolic counterpart. Compromised relaxation or increased stiffness of the left ventricle induces an increase in the upstream pulmonary pressures, and is classified as secondary or group II pulmonary hypertension (2018 Nice classification). This may result in an increase in the right ventricular afterload leading to right ventricular failure. Elevated pulmonary pressures are therefore an important clinical indicator of diastolic heart failure (sometimes referred to as heart failure with preserved ejection fraction, HFpEF), showing significant correlation with associated mortality. However, accurate measurements of this quantity are typically obtained through invasive catheterization and after the onset of symptoms. In this study, we use the hemodynamic consistency of a differential-algebraic circulation model to predict pulmonary pressures in adult patients from other, possibly non-invasive, clinical data. We investigate several aspects of the problem, including the ability of model outputs to represent a sufficiently wide pathologic spectrum, the identifiability of the model's parameters, and the accuracy of the predicted pulmonary pressures. We also find that a classifier using the assimilated model parameters as features is free from the problem of missing data and is able to detect pulmonary hypertension with sufficiently high accuracy. For a cohort of 82 patients suffering from various degrees of heart failure severity, we show that systolic, diastolic, and wedge pulmonary pressures can be estimated on average within 8, 6, and 6 mmHg, respectively. We also show that, in general, increased data availability leads to improved predictions.

scholarly journals Predictive modeling of secondary pulmonary hypertension in left ventricular diastolic dysfunction

2020 ◽  
Author(s):  
K. K. Harrod ◽  
J. L. Rogers ◽  
J. A. Feinstein ◽  
A. L. Marsden ◽  
D. E. Schiavazzi
Keyword(s):  
Heart Failure ◽  
Pulmonary Hypertension ◽  
Right Ventricular ◽  
Diastolic Dysfunction ◽  
Diastolic Heart Failure ◽  
Circulation Model ◽  
Left Ventricular ◽  
Data Availability ◽  
Model Parameters ◽  
Ventricular Afterload

AbstractDiastolic dysfunction is a common pathology occurring in about one third of patients affected by heart failure. This condition is not associated with a marked decrease in cardiac output or systemic pressure and therefore is more difficult to diagnose then its systolic counterpart. Compromised relaxation or increased stiffness of the left ventricle with or without mitral valve stenosis induces an increase in the upstream pulmonary pressures, and classified as secondary or group II (2018 Nice classification) pulmonary hypertension. This may result in an increase in the right ventricular afterload leading to right ventricular failure. Elevated pulmonary pressures are therefore an important clinical indicator of diastolic heart failure (sometimes referred to as heart failure with preserved ejection fraction), showing significant correlation with associated mortality. Accurate measurements of this quantity, however, are typically obtained through invasive catheterization, and after the onset of symptoms. In this study, we use the hemodynamic consistency of a differential-algebraic circulation model to predict pulmonary pressures in adult patients from other, possibly non-invasive, clinical data. We investigate several aspects of the problem, including the well posedness of a modeling approach for this type of disease, identifiability of its parameters, to the accuracy of the predicted pulmonary pressures. We also find that a classifier using the assimilated model parameters as features is free from the problem of missing data and is able to detect pulmonary hypertension with sufficiently high accuracy. For a cohort of 82 patients suffering from various degrees of heart failure severity we show that systolic, diastolic and wedge pulmonary pressures can be estimated on average within 8, 6 and 6 mmHg, respectively. We also show that, in general, increased data availability leads to improved predictions.

scholarly journals Heart failure with Preserved EF: A Bird Eye View

2013 ◽  
Vol 52 (190) ◽  
Author(s):  
Fahad Aziz ◽  
Luqman-Arfath Thazhatauveetil-Kunhahamed ◽  
Chijioke Enweluzo ◽  
Misbah Zaeem
Keyword(s):  
Heart Failure ◽  
Diastolic Dysfunction ◽  
Early Recognition ◽  
Systolic Function ◽  
Diastolic Heart Failure ◽  
Systolic Dysfunction ◽  
Hypertensive Heart Disease ◽  
Left Ventricular ◽  
Morbidity Rate ◽  
Annual Mortality

The concept of ‘‘diastolic’’ heart failure grew out of the observation that many patients who have the symptoms and signs of heart failure had an apparently normal left ventricular (LV) ejection fraction. Thus it was assumed that since systolic function was ‘‘pre- served’’ the problem must lie in diastole, although it is not clear by whom or when this assumption was made. Diastolic heart failure is associated with a lower annual mortality rate of approximately 8% as compared to annual mortality of 19% in heart failure with systolic dysfunction, however, morbidity rate can be substantial. Thus, diastolic heart failure is an important clinical disorder mainly seen in the elderly patients with hypertensive heart disease. Early recognition and appropriate therapy of diastolic dysfunction is advisable to prevent further progression to diastolic heart failure and death. There is no specific therapy to improve LV diastolic function directly. Medical therapy of diastolic dysfunction is often empirical and lacks clear-cut pathophysiologic concepts. Nevertheless, there is growing evidence that calcium channel blockers, beta-blockers, ACE-inhibitors and ARB as well as nitric oxide donors can be beneficial. Treatment of the underlying disease is currently the most important therapeutic approach.Keywords: diastolic heart failure; doppler echocardiography; treatment.

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