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Special Issue "Heart Failure: From Molecular Basis to Therapy"

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: 30 November 2019.

Special Issue Editors

Prof. Dr. Francesco Fedele
E-Mail Website
Guest Editor
Department of Cardiovascular, Respiratory, Nephrology, Anesthesiology and Geriatric Sciences, Sapienza University of Rome, 00161 Rome, Italy
Interests: heart failure; ischemic heart-disease; coronary microcirculation; pulmonary hypertension; cardiac magnetic-resonance
Special Issues and Collections in MDPI journals
Prof. Dr. Paul J. Mather
E-Mail Website
Guest Editor
Heart Failure—Transplant Program, Perelman School of Medicine, University of Pennsylvania, 2 East Perelman Center for Advanced Medicine, 3400 Civic Center Blvd, Philadelphia, PA 19104, USA
Interests: heart failure; ventricular assistance device; cardiac transplant

Special Issue Information

Dear Colleagues,

As is well known, globally, heart failure represents the epidemic of the third millennium in terms of prevalence, costs, and mortality. Despite prevention, efficient screening, and early-treatment programs, heart failure is still a great problem for both physicians and healthcare systems. The Special Issue “Heart Failure: From Molecular Basis to Therapy” aims to stimulate comprehensive research for a holistic approach. This Special Issue will accept articles on the pathophysiology of heart failure and its etiologies, molecular basis, multimodality imaging, echocardiography, magnetic resonance imaging, therapy including pharmacological and non-pharmacological treatment as implantable defibrillators, resynchronization therapy, ventricular assistance devices, and transplantation.

This Special Issue wants to focus on both basic science and translational researches as well as clinical evidences in order to have a more complete comprehension of the pathophysiology of heart failure, considering all the aspects of this complex puzzle.

Prof. Dr. Francesco Fedele
Prof. Dr. Paul J. Mather
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • heart failure
  • ischemic heart-disease
  • cardiomyopathy
  • pulmonary hypertension
  • pulmonary heart-disease
  • valve heart-disease
  • rhythm disorders
  • risk factors, ion channels
  • energy metabolism
  • inotropism
  • echocardiography
  • magnetic-resonance imaging
  • remodeling
  • ventricular assistant device
  • transplantation

Published Papers (7 papers)

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Research

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Open AccessArticle
Inducible Cardiac-Specific Deletion of Sirt1 in Male Mice Reveals Progressive Cardiac Dysfunction and Sensitization of the Heart to Pressure Overload
Int. J. Mol. Sci. 2019, 20(20), 5005; https://doi.org/10.3390/ijms20205005 - 10 Oct 2019
Abstract
Heart failure is associated with profound alterations of energy metabolism thought to play a major role in the progression of this syndrome. SIRT1 is a metabolic sensor of cellular energy and exerts essential functions on energy metabolism, oxidative stress response, apoptosis, or aging. [...] Read more.
Heart failure is associated with profound alterations of energy metabolism thought to play a major role in the progression of this syndrome. SIRT1 is a metabolic sensor of cellular energy and exerts essential functions on energy metabolism, oxidative stress response, apoptosis, or aging. Importantly, SIRT1 deacetylates the peroxisome proliferator-activated receptor gamma co-activator 1α (PGC-1α), the master regulator of energy metabolism involved in mitochondrial biogenesis and fatty acid utilization. However, the exact role of SIRT1 in controlling cardiac energy metabolism is still incompletely understood and conflicting results have been obtained. We generated a cardio-specific inducible model of Sirt1 gene deletion in mice (Sirt1ciKO) to decipher the role of SIRT1 in control conditions and following cardiac stress induced by pressure overload. SIRT1 deficiency induced a progressive cardiac dysfunction, without overt alteration in mitochondrial content or properties. Sixteen weeks after Sirt1 deletion an increase in mitochondrial reactive oxygen species (ROS) production and a higher rate of oxidative damage were observed, suggesting disruption of the ROS production/detoxification balance. Following pressure overload, cardiac dysfunction and alteration in mitochondrial properties were exacerbated in Sirt1ciKO mice. Overall the results demonstrate that SIRT1 plays a cardioprotective role on cardiac energy metabolism and thereby on cardiac function. Full article
(This article belongs to the Special Issue Heart Failure: From Molecular Basis to Therapy)
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Open AccessArticle
Normalizing Plasma Renin Activity in Experimental Dilated Cardiomyopathy: Effects on Edema, Cachexia, and Survival
Int. J. Mol. Sci. 2019, 20(16), 3886; https://doi.org/10.3390/ijms20163886 - 09 Aug 2019
Abstract
Heart failure (HF) patients frequently have elevated plasma renin activity. We examined the significance of elevated plasma renin activity in a translationally-relevant model of dilated cardiomyopathy (DCM), which replicates the progressive stages (A–D) of human HF. Female mice with DCM and elevated plasma [...] Read more.
Heart failure (HF) patients frequently have elevated plasma renin activity. We examined the significance of elevated plasma renin activity in a translationally-relevant model of dilated cardiomyopathy (DCM), which replicates the progressive stages (A–D) of human HF. Female mice with DCM and elevated plasma renin activity concentrations were treated with a direct renin inhibitor (aliskiren) in a randomized, blinded fashion beginning at Stage B HF. By comparison to controls, aliskiren treatment normalized pathologically elevated plasma renin activity (p < 0.001) and neprilysin levels (p < 0.001), but did not significantly alter pathological changes in plasma aldosterone, angiotensin II, atrial natriuretic peptide, or corin levels. Aliskiren improved cardiac systolic function (ejection fraction, p < 0.05; cardiac output, p < 0.01) and significantly reduced the longitudinal development of edema (extracellular water, p < 0.0001), retarding the transition from Stage B to Stage C HF. The normalization of elevated plasma renin activity reduced the loss of body fat and lean mass (cachexia/sarcopenia), p < 0.001) and prolonged survival (p < 0.05). In summary, the normalization of plasma renin activity retards the progression of experimental HF by improving cardiac systolic function, reducing the development of systemic edema, cachexia/sarcopenia, and mortality. These data suggest that targeting pathologically elevated plasma renin activity may be beneficial in appropriately selected HF patients. Full article
(This article belongs to the Special Issue Heart Failure: From Molecular Basis to Therapy)
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Review

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Open AccessReview
Heart Failure Differentially Modulates Natural (Sinoatrial Node) and Ectopic (Pulmonary Veins) Pacemakers: Mechanism and Therapeutic Implication for Atrial Fibrillation
Int. J. Mol. Sci. 2019, 20(13), 3224; https://doi.org/10.3390/ijms20133224 - 30 Jun 2019
Abstract
Heart failure (HF) frequently coexists with atrial fibrillation (AF) and dysfunction of the sinoatrial node (SAN), the natural pacemaker. HF is associated with chronic adrenergic stimulation, neurohormonal activation, abnormal intracellular calcium handling, elevated cardiac filling pressure and atrial stretch, and fibrosis. Pulmonary veins [...] Read more.
Heart failure (HF) frequently coexists with atrial fibrillation (AF) and dysfunction of the sinoatrial node (SAN), the natural pacemaker. HF is associated with chronic adrenergic stimulation, neurohormonal activation, abnormal intracellular calcium handling, elevated cardiac filling pressure and atrial stretch, and fibrosis. Pulmonary veins (PVs), which are the points of onset of ectopic electrical activity, are the most crucial AF triggers. A crosstalk between the SAN and PVs determines PV arrhythmogenesis. HF has different effects on SAN and PV electrophysiological characteristics, which critically modulate the development of AF and sick sinus syndrome. This review provides updates to improve our current understanding of the effects of HF in the electrical activity of the SAN and PVs as well as therapeutic implications for AF. Full article
(This article belongs to the Special Issue Heart Failure: From Molecular Basis to Therapy)
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Open AccessReview
Endothelial Dysfunction in Chronic Heart Failure: Assessment, Findings, Significance, and Potential Therapeutic Targets
Int. J. Mol. Sci. 2019, 20(13), 3198; https://doi.org/10.3390/ijms20133198 - 29 Jun 2019
Abstract
Chronic heart failure (CHF) is a complex syndrome that results from structural and functional disturbances that affect the ability of the heart to supply oxygen to tissues. It largely affects and reduces the patient’s quality of life, socio-economic status, and imposes great costs [...] Read more.
Chronic heart failure (CHF) is a complex syndrome that results from structural and functional disturbances that affect the ability of the heart to supply oxygen to tissues. It largely affects and reduces the patient’s quality of life, socio-economic status, and imposes great costs on health care systems worldwide. Endothelial dysfunction (ED) is a newly discovered phenomenon that contributes greatly to the pathophysiology of numerous cardiovascular conditions and commonly co-exists with chronic heart failure. However, the literature lacks clarity as to which heart failure patients might be affected, its significance in CHF patients, and its reversibility with pharmacological and non-pharmacological means. This review will emphasize all these points and summarize them for future researchers interested in vascular pathophysiology in this particular patient population. It will help to direct future studies for better characterization of these two phenomena for the potential discovery of therapeutic targets that might reduce future morbidity and mortality in this “at risk” population. Full article
(This article belongs to the Special Issue Heart Failure: From Molecular Basis to Therapy)
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Open AccessReview
Renin Activity in Heart Failure with Reduced Systolic Function—New Insights
Int. J. Mol. Sci. 2019, 20(13), 3182; https://doi.org/10.3390/ijms20133182 - 28 Jun 2019
Cited by 1
Abstract
Regardless of the cause, symptomatic heart failure (HF) with reduced ejection fraction (rEF) is characterized by pathological activation of the renin–angiotensin–aldosterone system (RAAS) with sodium retention and extracellular fluid expansion (edema). Here, we review the role of active renin, a crucial, upstream enzymatic [...] Read more.
Regardless of the cause, symptomatic heart failure (HF) with reduced ejection fraction (rEF) is characterized by pathological activation of the renin–angiotensin–aldosterone system (RAAS) with sodium retention and extracellular fluid expansion (edema). Here, we review the role of active renin, a crucial, upstream enzymatic regulator of the RAAS, as a prognostic and diagnostic plasma biomarker of heart failure with reduced ejection fraction (HFrEF) progression; we also discuss its potential as a pharmacological bio-target in HF therapy. Clinical and experimental studies indicate that plasma renin activity is elevated with symptomatic HFrEF with edema in patients, as well as in companion animals and experimental models of HF. Plasma renin activity levels are also reported to be elevated in patients and animals with rEF before the development of symptomatic HF. Modulation of renin activity in experimental HF significantly reduces edema formation and the progression of systolic dysfunction and improves survival. Thus, specific assessment and targeting of elevated renin activity may enhance diagnostic and therapeutic precision to improve outcomes in appropriate patients with HFrEF. Full article
(This article belongs to the Special Issue Heart Failure: From Molecular Basis to Therapy)
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Open AccessReview
Diagnostic and Treatment Approaches Involving Transthyretin in Amyloidogenic Diseases
Int. J. Mol. Sci. 2019, 20(12), 2982; https://doi.org/10.3390/ijms20122982 - 18 Jun 2019
Abstract
Transthyretin (TTR) is a thyroid hormone-binding protein which transports thyroxine from the bloodstream to the brain. The structural stability of TTR in tetrameric form is crucial for maintaining its original functions in blood or cerebrospinal fluid (CSF). The altered structure of TTR due [...] Read more.
Transthyretin (TTR) is a thyroid hormone-binding protein which transports thyroxine from the bloodstream to the brain. The structural stability of TTR in tetrameric form is crucial for maintaining its original functions in blood or cerebrospinal fluid (CSF). The altered structure of TTR due to genetic mutations or its deposits due to aggregation could cause several deadly diseases such as cardiomyopathy and neuropathy in autonomic, motor, and sensory systems. The early diagnoses for hereditary amyloid TTR with cardiomyopathy (ATTR-CM) and wild-type amyloid TTR (ATTRwt) amyloidosis, which result from amyloid TTR (ATTR) deposition, are difficult to distinguish due to the close similarities of symptoms. Thus, many researchers investigated the role of ATTR as a biomarker, especially its potential for differential diagnosis due to its varying pathogenic involvement in hereditary ATTR-CM and ATTRwt amyloidosis. As a result, the detection of ATTR became valuable in the diagnosis and determination of the best course of treatment for ATTR amyloidoses. Assessing the extent of ATTR deposition and genetic analysis could help in determining disease progression, and thus survival rate could be improved following the determination of the appropriate course of treatment for the patient. Here, the perspectives of ATTR in various diseases were presented. Full article
(This article belongs to the Special Issue Heart Failure: From Molecular Basis to Therapy)
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Open AccessReview
Inflammatory and Molecular Pathways in Heart Failure—Ischemia, HFpEF and Transthyretin Cardiac Amyloidosis
Int. J. Mol. Sci. 2019, 20(9), 2322; https://doi.org/10.3390/ijms20092322 - 10 May 2019
Cited by 1
Abstract
Elevated pro-inflammatory biomarkers and cytokines are associated with morbidity and mortality in heart failure (HF). Preclinical and clinical studies have shown multiple inflammatory mechanisms causing cardiac remodeling, dysfunction and chronic failure. Therapeutics in trials targeting the immune response in heart failure and its [...] Read more.
Elevated pro-inflammatory biomarkers and cytokines are associated with morbidity and mortality in heart failure (HF). Preclinical and clinical studies have shown multiple inflammatory mechanisms causing cardiac remodeling, dysfunction and chronic failure. Therapeutics in trials targeting the immune response in heart failure and its effects did not result in evident benefits regarding clinical endpoints and mortality. This review elaborates pathways of immune cytokines in pathogenesis and worsening of heart failure in clinical and cellular settings. Besides the well-known mechanisms of immune activation and inflammation in atherosclerosis causing ischemic cardiomyopathy or myocarditis, attention is focused on other mechanisms leading to heart failure such as transthyretin (TTR) amyloidosis or heart failure with preserved ejection fraction. The knowledge of the pathogenesis in heart failure and amyloidosis on a molecular and cellular level might help to highlight new disease defining biomarkers and to lead the way to new therapeutic targets. Full article
(This article belongs to the Special Issue Heart Failure: From Molecular Basis to Therapy)
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