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Nature Reviews. Cardiology Jul 2018Cardiomyocytes exit the cell cycle and become terminally differentiated soon after birth. Therefore, in the adult heart, instead of an increase in cardiomyocyte number,... (Review)
Review
Cardiomyocytes exit the cell cycle and become terminally differentiated soon after birth. Therefore, in the adult heart, instead of an increase in cardiomyocyte number, individual cardiomyocytes increase in size, and the heart develops hypertrophy to reduce ventricular wall stress and maintain function and efficiency in response to an increased workload. There are two types of hypertrophy: physiological and pathological. Hypertrophy initially develops as an adaptive response to physiological and pathological stimuli, but pathological hypertrophy generally progresses to heart failure. Each form of hypertrophy is regulated by distinct cellular signalling pathways. In the past decade, a growing number of studies have suggested that previously unrecognized mechanisms, including cellular metabolism, proliferation, non-coding RNAs, immune responses, translational regulation, and epigenetic modifications, positively or negatively regulate cardiac hypertrophy. In this Review, we summarize the underlying molecular mechanisms of physiological and pathological hypertrophy, with a particular emphasis on the role of metabolic remodelling in both forms of cardiac hypertrophy, and we discuss how the current knowledge on cardiac hypertrophy can be applied to develop novel therapeutic strategies to prevent or reverse pathological hypertrophy.
Topics: Adaptation, Physiological; Animals; Cardiomegaly; Cardiomegaly, Exercise-Induced; Energy Metabolism; Heart Ventricles; Humans; Mitochondria, Heart; Myocardium; Regeneration; Signal Transduction; Ventricular Remodeling
PubMed: 29674714
DOI: 10.1038/s41569-018-0007-y -
Archives of Toxicology Sep 2015The onset of heart failure is typically preceded by cardiac hypertrophy, a response of the heart to increased workload, a cardiac insult such as a heart attack or... (Review)
Review
The onset of heart failure is typically preceded by cardiac hypertrophy, a response of the heart to increased workload, a cardiac insult such as a heart attack or genetic mutation. Cardiac hypertrophy is usually characterized by an increase in cardiomyocyte size and thickening of ventricular walls. Initially, such growth is an adaptive response to maintain cardiac function; however, in settings of sustained stress and as time progresses, these changes become maladaptive and the heart ultimately fails. In this review, we discuss the key features of pathological cardiac hypertrophy and the numerous mediators that have been found to be involved in the pathogenesis of cardiac hypertrophy affecting gene transcription, calcium handling, protein synthesis, metabolism, autophagy, oxidative stress and inflammation. We also discuss new mediators including signaling proteins, microRNAs, long noncoding RNAs and new findings related to the role of calcineurin and calcium-/calmodulin-dependent protein kinases. We also highlight mediators and processes which contribute to the transition from adaptive cardiac remodeling to maladaptive remodeling and heart failure. Treatment strategies for heart failure commonly include diuretics, angiotensin converting enzyme inhibitors, angiotensin II receptor blockers and β-blockers; however, mortality rates remain high. Here, we discuss new therapeutic approaches (e.g., RNA-based therapies, dietary supplementation, small molecules) either entering clinical trials or in preclinical development. Finally, we address the challenges that remain in translating these discoveries to new and approved therapies for heart failure.
Topics: Animals; Cardiomegaly; Heart Failure; Heart Ventricles; Humans; Myocytes, Cardiac; Signal Transduction
PubMed: 25708889
DOI: 10.1007/s00204-015-1477-x -
Current Hypertension Reports Feb 2020Given that the life expectancy and the burden of hypertension are projected to increase over the next decade, hypertensive heart disease (HHD) may be expected to play an... (Review)
Review
PURPOSE OF REVIEW
Given that the life expectancy and the burden of hypertension are projected to increase over the next decade, hypertensive heart disease (HHD) may be expected to play an even more central role in the pathophysiology of cardiovascular disease (CVD). A broader understanding of the features and underlying mechanisms that constitute HHD therefore is of paramount importance.
RECENT FINDINGS
HHD is a condition that arises as a result of elevated blood pressure and constitutes a key underlying mechanism for cardiovascular morbidity and mortality. Historically, studies investigating HHD have primarily focused on left ventricular (LV) hypertrophy (LVH), but it is increasingly apparent that HHD encompasses a range of target-organ damage beyond LVH, including other cardiovascular structural and functional adaptations that may occur separately or concomitantly. HHD is characterized by micro- and macroscopic myocardial alterations, structural phenotypic adaptations, and functional changes that include cardiac fibrosis, and the remodeling of the atria and ventricles and the arterial system. In this review, we summarize the structural and functional alterations in the cardiac and vascular system that constitute HHD and underscore their underlying pathophysiology.
Topics: Heart Diseases; Heart Ventricles; Humans; Hypertension; Hypertrophy, Left Ventricular; Myocardium
PubMed: 32016791
DOI: 10.1007/s11906-020-1017-9 -
Journal of the American College of... Nov 2020
Topics: Cholesterol; Heart Ventricles; Humans; Hypertrophy; Lipids; Mendelian Randomization Analysis
PubMed: 33213728
DOI: 10.1016/j.jacc.2020.10.004 -
Journal of Human Hypertension Jan 2015Left ventricular (LV) hypertrophy and remodeling are frequently seen in hypertensive subjects and result from a complex interaction of several hemodynamic and... (Review)
Review
Left ventricular (LV) hypertrophy and remodeling are frequently seen in hypertensive subjects and result from a complex interaction of several hemodynamic and non-hemodynamic variables. Although increased blood pressure is considered the major determinant of LV structural alterations, ethnicity, gender, environmental factors, such as salt intake, obesity and diabetes mellitus, as well as neurohumoral and genetic factors might influence LV mass and geometry. The conventional concept of hypertensive LV remodeling has been that hypertension leads to concentric hypertrophy, as an adaptive response to normalize wall stress, which is then followed by chamber dilation and heart failure. However, several lines of evidence have challenged this dogma. Concentric hypertrophy is not the most frequent geometric pattern and is less usually seen than eccentric hypertrophy in hypertensive subjects. In addition, data from recent studies suggested that transition from LV concentric hypertrophy to dilation and systolic dysfunction is not a common finding, especially in the absence of coronary heart disease. LV hypertrophy is also consistently associated with increased cardiovascular morbidity and mortality, raising doubts whether this phenotype is an adaptive response. Experimental evidence exists that a blunting of load-induced cardiomyocyte hypertrophy does not necessarily result in LV dysfunction or failure. Furthermore, the hypertrophic myocardium shows fibrosis, alterations in the coronary circulation and cardiomyocyte apoptosis, which may result in heart failure, myocardial ischemia and arrhythmias. Overall, this body of evidence suggests that LV hypertrophy is a complex phenotype that predicts adverse cardiovascular outcomes and may not be necessarily considered as an adaptive response to systemic hypertension.
Topics: Animals; Blood Pressure; Fibrosis; Heart Ventricles; Humans; Hypertension; Hypertrophy, Left Ventricular; Prognosis; Risk Assessment; Risk Factors; Ventricular Function, Left; Ventricular Remodeling
PubMed: 24804791
DOI: 10.1038/jhh.2014.36 -
Circulation Jan 2019The role of right ventricular (RV) fibrosis in pulmonary hypertension (PH) remains a subject of ongoing discussion. Alterations of the collagen network of the...
The role of right ventricular (RV) fibrosis in pulmonary hypertension (PH) remains a subject of ongoing discussion. Alterations of the collagen network of the extracellular matrix may help prevent ventricular dilatation in the pressure-overloaded RV. At the same time, fibrosis impairs cardiac function, and a growing body of experimental data suggests that fibrosis plays a crucial role in the development of RV failure. In idiopathic pulmonary arterial hypertension and chronic thromboembolic PH, the RV is exposed to a ≈5 times increased afterload, which makes these conditions excellent models for studying the impact of pressure overload on RV structure. With this review, we present clinical evidence of RV fibrosis in idiopathic pulmonary arterial hypertension and chronic thromboembolic PH, explore the correlation between fibrosis and RV function, and discuss the clinical relevance of RV fibrosis in patients with PH. We postulate that RV fibrosis has a dual role in patients with pressure-overloaded RVs of idiopathic pulmonary arterial hypertension and chronic thromboembolic PH: as part of an adaptive response to prevent cardiomyocyte overstretch and to maintain RV shape for optimal function, and as part of a maladaptive response that increases diastolic stiffness, perturbs cardiomyocyte excitation-contraction coupling, and disrupts the coordination of myocardial contraction. Finally, we discuss potential novel therapeutic strategies and describe more sensitive techniques to quantify RV fibrosis, which may be used to clarify the causal relation between RV fibrosis and RV function in future research.
Topics: Adaptation, Physiological; Animals; Arterial Pressure; Extracellular Matrix; Fibrosis; Heart Failure; Heart Ventricles; Humans; Hypertension, Pulmonary; Hypertrophy, Right Ventricular; Myocardium; Prognosis; Pulmonary Artery; Ventricular Dysfunction, Right; Ventricular Function, Right; Ventricular Remodeling
PubMed: 30615500
DOI: 10.1161/CIRCULATIONAHA.118.035326 -
High Blood Pressure & Cardiovascular... Mar 2015Obesity can be regarded as an energy balance disorder in which inappropriate expansion and dys-function of adipose tissue lead to unfavorable outcomes. Even in the... (Review)
Review
Obesity can be regarded as an energy balance disorder in which inappropriate expansion and dys-function of adipose tissue lead to unfavorable outcomes. Even in the absence of hypertension, adiposity induces structural and functional changes in the heart through hemodynamic and non hemodynamic factors. In the "obese" heart, besides the growth of cardiomyocytes, interstitial fat infiltration and triglyceride accumulation in the contractile elements importantly contribute to left-ventricular mass (LVM) accrual, hypertrophy (LVH) and geometric pattern. In harmony with this, the likelihood of LVH is greater in either obese normotensive or hypertensive individuals than in their non-obese counterparts. Interestingly, recent observations highlight the increasing prevalence of the "concentric" (ie, combined remodeling and hypertrophy), rather than "eccentric" pattern of LV geometry in obesity. Nonetheless, obesity is linked with lack of decrease, or even increase, of LVM over time, independently of blood pressure control and hypertensive treatment. Although obesity-related LV changes result in progressive systolic and diastolic heart failure, the assessment of LVM and LVH in obese individuals still remains a difficult task. In this scenario, it is tempting to speculate that therapeutic interventions for reversal of LVH in obesity should either overcome the "non-hemodynamic" factors or reduce the hemodynamic load. Indeed, weight loss, either achieved by lifestyle changes or bariatric procedures, decreases LVM and improves LV function regardless of blood pressure status. These and other mechanistic insights are discussed in this review, which focuses on "adipose dysfunction" as potential instigator of, and putative therapeutic target for, LVH regression in the setting of obesity.
Topics: Adipose Tissue; Adiposity; Animals; Energy Metabolism; Heart Ventricles; Humans; Hypertrophy, Left Ventricular; Obesity; Prognosis; Risk Factors; Ventricular Function, Left; Ventricular Remodeling
PubMed: 25117210
DOI: 10.1007/s40292-014-0068-x -
Heart Failure Clinics Apr 2019Several left ventricular geometric patterns have been described both in healthy and pathologic hearts. Left ventricular mass, wall thickness, and the ratio of wall... (Review)
Review
Several left ventricular geometric patterns have been described both in healthy and pathologic hearts. Left ventricular mass, wall thickness, and the ratio of wall thickness to radius are important measures to characterize the spectrum of left ventricular geometry. For clinicians, an increase in left ventricular mass is the hallmark of left ventricular hypertrophy. Although pathologic hypertrophy initially can be compensatory, eventually it may become maladaptive and evolve toward progressive left ventricular dysfunction and heart failure. In particular, patients who show left ventricular dilation and hypertrophy in association with a low relative wall thickness are likely to carry the highest risk.
Topics: Echocardiography; Heart Failure; Heart Ventricles; Humans; Hypertrophy, Left Ventricular; Ventricular Dysfunction, Left
PubMed: 30832808
DOI: 10.1016/j.hfc.2018.12.013 -
Journal of Medical Ultrasonics (2001) Apr 2024The initial means of detecting right ventricular (RV) dilatation is often transthoracic echocardiography (TTE), and once the presence of RV dilatation is suspected,... (Review)
Review
The initial means of detecting right ventricular (RV) dilatation is often transthoracic echocardiography (TTE), and once the presence of RV dilatation is suspected, there is the possibility of RV volume overload, RV pressure overload, RV myocardial disease, and even nonpathological RV dilatation. With respect to congenital heart disease with RV volume overload, defects or valvular abnormalities can be easily detected with TTE, with the exception of some diseases. Volumetric assessment using three-dimensional echocardiography may be useful in determining the intervention timing in these diseases. When the disease progresses in patients with pulmonary hypertension as a result of RV pressure overload, RV dilatation becomes more prominent than hypertrophy, and RV functional parameters predict the prognosis at this stage of maladaptive remodeling. The differential diagnosis of cardiomyopathy or comparison with nonpathological RV dilatation may be difficult in the setting of RV myocardial disease. The characteristics of RV functional parameters such as two-dimensional speckle tracking may help differentiate RV cardiomyopathy from other conditions. We review the diseases presenting with RV dilatation, their characteristics, and echocardiographic findings and parameters that are significant in assessing their status or intervention timing.
Topics: Humans; Diagnosis, Differential; Echocardiography; Heart Ventricles; Ventricular Dysfunction, Right; Hypertrophy, Right Ventricular; Echocardiography, Three-Dimensional; Dilatation, Pathologic; Hypertension, Pulmonary
PubMed: 38228943
DOI: 10.1007/s10396-023-01399-4 -
JACC. Cardiovascular Imaging Aug 2019Aortic stenosis (AS) causes left ventricular remodeling (hypertrophy, remodeling, fibrosis) and other cardiac changes (left atrial dilatation, pulmonary artery and... (Review)
Review
Aortic stenosis (AS) causes left ventricular remodeling (hypertrophy, remodeling, fibrosis) and other cardiac changes (left atrial dilatation, pulmonary artery and right ventricular changes). These changes, and whether they are reversible (reverse remodeling), are major determinants of timing and outcome from transcatheter or surgical aortic valve replacement. Cardiac changes in response to AS afterload can either be adaptive and reversible, or maladaptive and irreversible, when they may convey residual risk after intervention. Structural and hemodynamic assessment of AS therefore needs to evaluate more than the valve, and, in particular, the myocardial remodeling response. Imaging plays a key role in this. This review assesses how multimodality imaging evaluates AS myocardial hypertrophy and its components (cellular hypertrophy, fibrosis, microvascular changes, and additional features such as cardiac amyloid) both before and after intervention, and seeks to highlight how care and outcomes in AS could be improved.
Topics: Aortic Valve Stenosis; Echocardiography; Fibrosis; Heart Valve Prosthesis Implantation; Heart Ventricles; Humans; Hypertrophy, Left Ventricular; Magnetic Resonance Imaging; Multimodal Imaging; Predictive Value of Tests; Prognosis; Tomography, X-Ray Computed; Ventricular Function, Left; Ventricular Remodeling
PubMed: 31395243
DOI: 10.1016/j.jcmg.2019.02.034