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Cardiology Clinics May 2020Right-sided heart failure (RHF) occurs from impaired contractility of the right ventricle caused by pressure, volume overload, or intrinsic myocardial contractile... (Review)
Review
Right-sided heart failure (RHF) occurs from impaired contractility of the right ventricle caused by pressure, volume overload, or intrinsic myocardial contractile dysfunction. The development of subclinical right ventricle (RV) dysfunction or overt RHF is a negative prognostic indicator. Recent attention has focused on RV-specific inflammatory growth factors and mediators of myocardial fibrosis to elucidate the mechanisms leading to RHF and potentially guide the development of novel therapeutics. This article focuses on the distinct changes in RV structure, mechanics, and function, as well as molecular and inflammatory mediators involved in the pathophysiology of acute and chronic RHF.
Topics: Acute Disease; Disease Progression; Heart Failure; Heart Ventricles; Humans; Myocardial Contraction; Ventricular Dysfunction, Right; Ventricular Function, Right
PubMed: 32284093
DOI: 10.1016/j.ccl.2020.01.009 -
American Journal of Respiratory and... Sep 2022Pulmonary arterial hypertension (PAH) often results in death from right ventricular failure (RVF). NLRP3 (nucleotide-binding domain, leucine-rich-containing family,...
Pulmonary arterial hypertension (PAH) often results in death from right ventricular failure (RVF). NLRP3 (nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3)-macrophage activation may promote RVF in PAH. Evaluating the contribution of the NLRP3 inflammasome in RV macrophages to PAH RVF. Rats with decompensated RV hypertrophy (monocrotaline [MCT] and Sugen-5416 hypoxia [SuHx]) were compared with compensated RV hypertrophy rats (pulmonary artery banding). Echocardiography and right heart catheterization were performed. Macrophages, atrial natriuretic peptides, and fibrosis were evaluated by microscopy or flow cytometry. NLRP3 inflammasome activation and cardiotoxicity were confirmed by immunoblot and strategies. MCT rats were treated with SC-144 (a GP130 antagonist) or MCC950 (an NLRP3 inhibitor). Macrophage-NLRP3 activity was evaluated in patients with PAH RVF. Macrophages, fibrosis, and atrial natriuretic peptides were increased in MCT and SuHx RVs but not in left ventricles or pulmonary artery banding rats. Although MCT RV macrophages were inflammatory, lung macrophages were antiinflammatory. CCR2 macrophages (monocyte-derived) were increased in MCT and SuHx RVs and highly expressed NLRP3. The macrophage-NLRP3 pathway was upregulated in patients with PAH with decompensated RVs. Cultured MCT monocytes showed NLRP3 activation, and in coculture experiments resulted in cardiomyocyte mitochondrial damage, which MCC950 prevented. , MCC950 reduced NLRP3 activation and regressed pulmonary vascular disease and RVF. SC-144 reduced RV macrophages and NLRP3 content, prevented STAT3 (signal transducer and activator of transcription 3) activation, and improved RV function without regressing pulmonary vascular disease. NLRP3-macrophage activation occurs in the decompensated RV in preclinical PAH models and patients with PAH. Inhibiting GP130 or NLRP3 signaling improves RV function. The concept that PAH RVF results from RV inflammation rather than solely from elevated RV afterload suggests a new therapeutic paradigm.
Topics: Animals; Atrial Natriuretic Factor; Cytokine Receptor gp130; Disease Models, Animal; Familial Primary Pulmonary Hypertension; Fibrosis; Heart Failure; Heart Ventricles; Hypertension, Pulmonary; Hypertrophy, Right Ventricular; Inflammasomes; Macrophage Activation; Macrophages; Monocrotaline; NLR Family, Pyrin Domain-Containing 3 Protein; Pulmonary Arterial Hypertension; Rats; Ventricular Dysfunction, Right
PubMed: 35699679
DOI: 10.1164/rccm.202110-2274OC -
Canadian Journal of Physiology and... Feb 2020The heart is capable of responding to stressful situations by increasing muscle mass, which is broadly defined as cardiac hypertrophy. This phenomenon minimizes... (Review)
Review
The heart is capable of responding to stressful situations by increasing muscle mass, which is broadly defined as cardiac hypertrophy. This phenomenon minimizes ventricular wall stress for the heart undergoing a greater than normal workload. At initial stages, cardiac hypertrophy is associated with normal or enhanced cardiac function and is considered to be adaptive or physiological; however, at later stages, if the stimulus is not removed, it is associated with contractile dysfunction and is termed as pathological cardiac hypertrophy. It is during physiological cardiac hypertrophy where the function of subcellular organelles, including the sarcolemma, sarcoplasmic reticulum, mitochondria, and myofibrils, may be upregulated, while pathological cardiac hypertrophy is associated with downregulation of these subcellular activities. The transition of physiological cardiac hypertrophy to pathological cardiac hypertrophy may be due to the reduction in blood supply to hypertrophied myocardium as a consequence of reduced capillary density. Oxidative stress, inflammatory processes, Ca-handling abnormalities, and apoptosis in cardiomyocytes are suggested to play a critical role in the depression of contractile function during the development of pathological hypertrophy.
Topics: Animals; Apoptosis; Calcium; Cardiomegaly; Cytokines; Humans; Intracellular Space
PubMed: 31815523
DOI: 10.1139/cjpp-2019-0566 -
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 -
Nature Cell Biology Nov 2020PIWI-interacting RNAs (piRNAs) are abundantly expressed during cardiac hypertrophy. However, their functions and molecular mechanisms remain unknown. Here, we identified...
PIWI-interacting RNAs (piRNAs) are abundantly expressed during cardiac hypertrophy. However, their functions and molecular mechanisms remain unknown. Here, we identified a cardiac-hypertrophy-associated piRNA (CHAPIR) that promotes pathological hypertrophy and cardiac remodelling by targeting METTL3-mediated N-methyladenosine (mA) methylation of Parp10 mRNA transcripts. CHAPIR deletion markedly attenuates cardiac hypertrophy and restores heart function, while administration of a CHAPIR mimic enhances the pathological hypertrophic response in pressure-overloaded mice. Mechanistically, CHAPIR-PIWIL4 complexes directly interact with METTL3 and block the mA methylation of Parp10 mRNA transcripts, which upregulates PARP10 expression. The CHAPIR-dependent increase in PARP10 promotes the mono-ADP-ribosylation of GSK3β and inhibits its kinase activity, which results in the accumulation of nuclear NFATC4 and the progression of pathological hypertrophy. Hence, our findings reveal that a piRNA-mediated RNA epigenetic mechanism is involved in the regulation of cardiac hypertrophy and that the CHAPIR-METTL3-PARP10-NFATC4 signalling axis could be therapeutically targeted for treating pathological hypertrophy and maladaptive cardiac remodelling.
Topics: Adenosine; Animals; Cells, Cultured; Disease Models, Animal; Gene Expression Regulation, Enzymologic; Glycogen Synthase Kinase 3 beta; Heart Ventricles; Hypertrophy, Left Ventricular; Male; Methylation; Methyltransferases; Mice, Inbred C57BL; Mice, Knockout; Myocytes, Cardiac; NFATC Transcription Factors; Poly(ADP-ribose) Polymerases; Proto-Oncogene Proteins; RNA Stability; RNA, Messenger; RNA, Small Interfering; Signal Transduction; Ventricular Function, Left; Ventricular Remodeling
PubMed: 33020597
DOI: 10.1038/s41556-020-0576-y -
Journal of the American College of... Aug 2023Ventricular mass responds to changes in physical activity and loading, with cardiac hypertrophy after exercise training, and cardiac atrophy after sustained inactivity....
BACKGROUND
Ventricular mass responds to changes in physical activity and loading, with cardiac hypertrophy after exercise training, and cardiac atrophy after sustained inactivity. Ventricular wall stress (ie, loading) decreases during microgravity. Cardiac atrophy does not plateau during 12 weeks of simulated microgravity but is mitigated by concurrent exercise training.
OBJECTIVES
The goal of this study was to determine whether the current exercise countermeasures on the International Space Station (ISS) offset cardiac atrophy during prolonged space flight.
METHODS
We measured left ventricular (LV) and right ventricular (RV) mass and volumes (via magnetic resonance imaging) in 13 astronauts (4 females; age 49 ± 4 years), between 75 and 60 days before and 3 days after 155 ± 31 days aboard the ISS. Furthermore, we assessed total cardiac work between 21 and 7 days before space flight and 15 days before the end of the mission. Data were compared via paired-samples t-tests.
RESULTS
Total cardiac work was lower during space flight (P = 0.008); however, we observed no meaningful difference in LV mass postflight (pre: 115 ± 30 g vs post: 118 ± 29 g; P = 0.053), with marginally higher LV stroke volume (P = 0.074) and ejection fraction postflight (P = 0.075). RV mass (P = 0.999), RV ejection fraction (P = 0.147), and ventricular end-diastolic (P = 0.934) and end-systolic volumes (P = 0.145) were not different postflight. There were strong positive correlations between the relative change in LV mass with the relative changes in total cardiac output (r = 0.73; P = 0.015) and total cardiac work (r = 0.53; P = 0.112).
CONCLUSIONS
The current exercise countermeasures used on the ISS appear effective in offsetting reductions in cardiac mass and volume, despite overall reductions in total cardiac work, during prolonged space flight.
Topics: Female; Humans; Middle Aged; Heart; Space Flight; Heart Ventricles; Atrophy; Cardiac Output
PubMed: 37587578
DOI: 10.1016/j.jacc.2023.05.058 -
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 the American Society of... Jun 2024Hypertrophic cardiomyopathy (HCM), the most common inherited cardiomyopathy, exhibits left ventricular hypertrophy not secondary to other causes, with varied phenotypic... (Review)
Review
Hypertrophic cardiomyopathy (HCM), the most common inherited cardiomyopathy, exhibits left ventricular hypertrophy not secondary to other causes, with varied phenotypic expression. Enhanced actin-myosin interaction underlies excessive myocardial contraction, frequently resulting in dynamic obstruction within the left ventricle. Left ventricular outflow tract obstruction, occurring at rest or with provocation in 75% of HCM patients, portends adverse prognosis, contributes to symptoms, and is frequently a therapeutic target. Transthoracic echocardiography plays a crucial role in the screening, initial diagnosis, management, and risk stratification of HCM. Herein, we explore echocardiographic evaluation of HCM, emphasizing Doppler assessment for obstruction. Echocardiography informs management strategies through noninvasive hemodynamic assessment, which is frequently obtained with various provocative maneuvers. Recognition of obstructive HCM phenotypes and associated anatomical abnormalities guides therapeutic decision-making. Doppler echocardiography allows monitoring of therapeutic responses, whether it be medical therapies (including cardiac myosin inhibitor therapy) or septal reduction therapies, including surgical myectomy and alcohol septal ablation. This article discusses the hemodynamics of obstruction and practical application of Doppler assessment in HCM. In addition, it provides a visual atlas of obstruction in HCM, including high-quality figures and complementary videos that illustrate the many facets of dynamic obstruction.
Topics: Humans; Cardiomyopathy, Hypertrophic; Ventricular Outflow Obstruction; Echocardiography, Doppler; Echocardiography; Heart Ventricles
PubMed: 38428652
DOI: 10.1016/j.echo.2024.02.010 -
Hypertension Research : Official... Jan 2023The aim of the study was to evaluate hypertension treatment effects on mechanical efficiency of the cardiovascular system and cardiac reverse remodeling in hypertensive... (Observational Study)
Observational Study
The aim of the study was to evaluate hypertension treatment effects on mechanical efficiency of the cardiovascular system and cardiac reverse remodeling in hypertensive patients. This is an observational prospective study, consecutive hypertension patients. Left ventricle mass index measured by Devereux 2D method and diastolic function following the Guidelines from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. Left ventricular end systolic elastance (Ees) was measured by Guarracino calculator, the effective arterial elastance (Ea) and ventricular-arterial coupling (VAC) measured by Sunagawa et al. single beat method adapted by Chen et al. in human ventricles. The sample was analyzed in quartiles (Q) according to VAC. Follow-up 2 years. In total, 288 patients, mean age 56.3 ± 12.5 years and 168 patients (58.3%) males. VAC increased from 0.303 ± 0.07 to 0.54 ± 0.25 (p < 0.005) in Q1 mainly due to a reduction in Ees from 5.25 ± 2.3 to 3.68 ± 0.25 mmHg/ml (p < 0.01), while Ea increased from 1.5 ± 0.53 to 1.64 ± 0.56 mmHg/ml (p = NS). The frequency of LVH was reduced from 31.9 to 10.8% in Q1 (p < 0.025). The frequency of normal diastolic function increased from 75 to 94.6% (p < 0.01) in Q1, from 78.7 to 100% in Q2 (p < 0.005), from 87.1 to 100% (p < 0.025) in Q3 and from 88.7 to 100% (0,025) in Q4. Patients with the worst ventricular-arterial uncoupling were the most benefited from hypertension treatment. Regression of left ventricular hypertrophy was observed only in the group of patients with the worst ventricular-arterial uncoupling, while improvement in diastolic function was demonstrated in all quartiles of patients.
Topics: Male; Humans; Adult; Middle Aged; Aged; Female; Heart Ventricles; Prospective Studies; Hypertension; Hypertrophy, Left Ventricular; Echocardiography; Ventricular Function, Left
PubMed: 36229532
DOI: 10.1038/s41440-022-01063-3 -
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