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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 -
Circulation Journal : Official Journal... 2013
Topics: Hair; Heart Ventricles; Humans; Hypertrophy, Left Ventricular; Magnesium; Male; Renal Dialysis
PubMed: 24200847
DOI: 10.1253/circj.cj-13-1294 -
Circulation Research Jul 2009Most sarcomere gene mutations that cause hypertrophic cardiomyopathy are missense alleles that encode dominant negative proteins. The potential exceptions are mutations...
RATIONALE
Most sarcomere gene mutations that cause hypertrophic cardiomyopathy are missense alleles that encode dominant negative proteins. The potential exceptions are mutations in the MYBPC3 gene (encoding cardiac myosin-binding protein-C [MyBP-C]), which frequently encode truncated proteins.
OBJECTIVE
We sought to determine whether there was evidence of haploinsufficiency in hypertrophic cardiomyopathy caused by MYBPC3 mutations by comparing left ventricular muscle from patients undergoing surgical myectomy with samples from donor hearts.
METHODS AND RESULTS
MyBP-C protein and mRNA levels were quantitated using immunoblotting and RT-PCR. Nine of 37 myectomy samples had mutations in MYBPC3: 2 missense alleles (Glu258Lys, Arg502Trp) and 7 premature terminations. No specific truncated MyBP-C peptides were detected in whole muscle homogenates of hypertrophic cardiomyopathy tissue. However, the overall level of MyBP-C in myofibrils was significantly reduced (P<0.0005) in tissue containing either a truncation or missense MYBPC3 mutation: 0.76+/-0.03 compared with 1.00+/-0.05 in donor and 1.01+/-0.06 in non-MYBPC3 mutant myectomies.
CONCLUSIONS
The absence of any detectable truncated MyBP-C argues against its incorporation in the myofiber and any dominant negative effect. In contrast, the lowered relative level of full length protein in both truncation and missense MYBPC3 mutations argues strongly that haploinsufficiency is sufficient to cause the disease.
Topics: Alleles; Carrier Proteins; Case-Control Studies; Genotype; Haploidy; Heart Ventricles; Humans; Hypertrophy, Left Ventricular; Mutation, Missense; Myocardium; RNA, Messenger
PubMed: 19574547
DOI: 10.1161/CIRCRESAHA.109.202440 -
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 -
Current Hypertension Reports Jun 2009The renin-angiotensin system (RAS), an important control system for blood pressure and intravascular volume, also causes left ventricular hypertrophy (LVH) and fibrosis.... (Review)
Review
The renin-angiotensin system (RAS), an important control system for blood pressure and intravascular volume, also causes left ventricular hypertrophy (LVH) and fibrosis. The main causal mechanism is the increase in blood pressure, which leads to increased left ventricular wall stress; however, aldosterone release from the adrenals and (more controversially) the direct action of angiotensin II on the cardiomyocytes also play a role. Large clinical trials evaluating the blockade of the RAS with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers have demonstrated an ability to prevent progression and induce regression of left ventricular mass, thereby reducing the significant and independent cardiovascular risk conferred by LVH. Regression of left ventricular mass is also achieved by other medication classes, but the RAS blockers have an additional beneficial effect for the same blood pressure reduction, for which the mechanism is not entirely clear. Studies comparing the efficacy of angiotensin-converting enzyme inhibitors versus angiotensin receptor blockers to achieve LVH regression have not demonstrated any clear benefit of one class over the other.
Topics: Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Animals; Heart Ventricles; Humans; Hypertrophy, Left Ventricular; Renin-Angiotensin System; Treatment Outcome
PubMed: 19442324
DOI: 10.1007/s11906-009-0030-9 -
BMC Cardiovascular Disorders Dec 2022Left ventricular (LV) geometry is closely associated with cardiovascular disease; however, few studies have evaluated the relationship between basal septal hypertrophy...
BACKGROUND
Left ventricular (LV) geometry is closely associated with cardiovascular disease; however, few studies have evaluated the relationship between basal septal hypertrophy (BSH) and LV geometry. In this study, we examined the relationship between BSH and LV geometry in a Beijing community population.
METHODS
The clinical and echocardiographic data of 1032 participants from a community in Beijing were analyzed. BSH was defined as a basal interventricular septal thickness ≥ 14 mm and a basal septal thickness/mid-septal thickness ≥ 1.3. On the basis of their echocardiographic characteristics, patients were described as having a normal geometry, concentric remodeling, concentric hypertrophy, or eccentric hypertrophy. Multivariable logistic regression was used to analyze the relationship between BSH, LV mass index (LVMI), and relative wall thickness (RWT).
RESULTS
The prevalence of BSH was 7.4% (95% confidence interval [CI] 5.8-9.0%). Basal and middle interventricular septal thickness, LV posterior wall thickness, and RWT were greater, while LVMI and LV end-diastolic dimension were lower in the BSH group than in the non-BSH group (p < 0.05). The BSH group accounted for the highest proportion of patients with concentric remodeling. A multivariable regression analysis showed that BSH increased by 3.99-times (odds ratio [OR] 3.99, 95% CI 2.05-7.78, p < 0.01) when RWT was > 0.42, but not when LVMI increased (OR 0.16, 95% CI 0.02-1.19, p = 0.07). There were no interactions between BSH and age, body mass index, sex, diabetes mellitus, coronary heart disease, stroke, and smoking in relation to an RWT > 0.42.
CONCLUSION
BSH was independently associated with an RWT > 0.42.
Topics: Humans; Hypertrophy, Left Ventricular; Echocardiography; Cardiovascular Diseases; Diabetes Mellitus; Heart Ventricles; Ventricular Remodeling
PubMed: 36587201
DOI: 10.1186/s12872-022-03004-x -
Scientific Reports Jun 2021Childhood obesity continues to escalate worldwide and may affect left ventricular (LV) geometry and function. The aim of this study was to investigate the impact of...
Childhood obesity continues to escalate worldwide and may affect left ventricular (LV) geometry and function. The aim of this study was to investigate the impact of obesity on prevalence of left ventricular hypertrophy (LVH) and diastolic dysfunction in children. In this analysis of prospectively collected cross-sectional data of children between 5 and 16 years of age from randomly selected schools in Peru, parameters of LV geometry and function were compared according to presence or absence of obesity (body mass index z-score > 2). LVH was based on left ventricular mass index (LVMI) adjusted for age and sex and defined by a z-score of > 2. LV diastolic function was assessed using mitral inflow early-to-late diastolic flow (E/A) ratio, peak early diastolic tissue velocities of the lateral mitral annulus (E'), early diastolic transmitral flow velocity to tissue Doppler mitral annular early diastolic velocity (E/E') ratio, and left atrial volume index (LAVI). Among 1023 children, 681 children (mean age 12.2 ± 3.1 years, 341 male (50.1%)) were available for the present analysis, of which 150 (22.0%) were obese. LVH was found in 21 (14.0%) obese and in 19 (3.6%) non-obese children (p < 0.001). LVMI was greater in obese than that in non-obese children (36.1 ± 8.6 versus 28.7 ± 6.9 g/m, p < 0.001). The mean mitral E/E' ratio and LAVI were significantly higher in obese than those in non-obese individuals (E/E': 5.2 ± 1.1 versus 4.9 ± 0.8, p = 0.043; LAVI 11.0 ± 3.2 versus 9.6 ± 2.9, p = 0.001), whereas E' and E/A ratio were comparable. Childhood obesity was associated with left ventricular hypertrophy and determinants of diastolic dysfunction.ClinicalTrials.gov Identifier: NCT02353663.
Topics: Adolescent; Body Mass Index; Child; Diastole; Female; Heart Ventricles; Humans; Hypertrophy, Left Ventricular; Male; Myocardium; Obesity; Organ Size
PubMed: 34158575
DOI: 10.1038/s41598-021-92463-x -
ESC Heart Failure Feb 2020In this study, we investigated the prognostic interplay of left ventricular hypertrophy and mechanical dyssynchrony (LVMD), both of which can be measured...
AIMS
In this study, we investigated the prognostic interplay of left ventricular hypertrophy and mechanical dyssynchrony (LVMD), both of which can be measured three-dimensionally by gated myocardial perfusion imaging (MPI), in patients with chronic systolic heart failure (HF).
METHODS AND RESULTS
In 829 consecutive HF patients with reduced left ventricular ejection fraction less than 50%, LVMD was evaluated as a standard deviation (phase SD) of regional onset of mechanical contraction phase angles. A phase histogram was created by Fourier phase analysis applied to regional time-activity curves obtained by gated MPI. Left ventricular mass index (LVMI) was measured by Corridor 4DM version 6.0. Patients were followed up with a primary endpoint of lethal cardiac events (CE) for a mean interval of 34 months. CE were documented in 223 (27%) of the HF patients. The CE group had a greater phase SD and a greater LVMI than those in the non-CE group. Patients in the CE group had a more advanced age, greater New York Heart Association (NYHA) functional class, left ventricular cavity size, and left atrial diameter or septal E/e' and lower kidney or cardiac function than did patients in the non-CE group. Phase SD > 37 and LVMI > 122.7 g/m were identified as optimal cut-off values by receiver operating characteristic analyses for discrimination of the most increased risk HF subgroup from others (P < 0.0001). When classified into four patient subgroups using both cut-off values, HF patients with phase SD > 37 (LVMD) and LVMI > 122.7g/m had the highest CE rate among the subgroups (P < 0.0001). Univariate analysis and subsequent multivariate analysis with a Cox proportional hazards model showed that phase SD and LVMI were significant independent predictors of CE with hazard ratios of 1.038 (confidence interval [CI], 1.024-1.051, P < 0.0001) and 1.005 (CI, 1.001-1.008, P = 0.0073), respectively, as well as conventional clinical parameters such as age, NYHA class, estimated glomerular filtration rate (eGFR), and BNP concentration. Patients with increased phase SD and LVMI had incrementally improved prognostic values of clinical parameters including age, NYHA functional class, eGFR, and BNP with increases in the global χ value: 5.9 for age; 139.5 for age and NYHA; 157.9 for age, NYHA, and eGFR; 163.9 for age, NYHA, eGFR, and BNP; 183.4 for age, NYHA, eGFR, BNP, and phase SD; and 192.5 for age, NYHA, eGFR, BNP, phase SD, and LVMI.
CONCLUSIONS
Three-dimensionally assessed LVMD has independent prognostic values and can improve the risk stratification of chronic HF patients synergistically in combination with conventional clinical parameters.
Topics: Aged; Female; Follow-Up Studies; Heart Failure, Systolic; Heart Ventricles; Humans; Hypertrophy, Left Ventricular; Imaging, Three-Dimensional; Male; Myocardial Perfusion Imaging; Prognosis; Retrospective Studies; Time Factors; Ventricular Function, Left
PubMed: 31965750
DOI: 10.1002/ehf2.12578 -
Clinics in Chest Medicine Mar 2021The right ventricle is coupled to the low-pressure pulmonary circulation. In pulmonary vascular diseases, right ventricular (RV) adaptation is key to maintain... (Review)
Review
The right ventricle is coupled to the low-pressure pulmonary circulation. In pulmonary vascular diseases, right ventricular (RV) adaptation is key to maintain ventriculoarterial coupling. RV hypertrophy is the first adaptation to diminish RV wall tension, increase contractility, and protect cardiac output. Unfortunately, RV hypertrophy cannot be sustained and progresses toward a maladaptive phenotype, characterized by dilation and ventriculoarterial uncoupling. The mechanisms behind the transition from RV adaptation to RV maladaptation and right heart failure are unraveled. Therefore, in this article, we explain the main traits of each phenotype, and how some early beneficial adaptations become prejudicial in the long-term.
Topics: Animals; Heart Ventricles; Humans; Hypertrophy, Right Ventricular; Mice; Rats; Ventricular Dysfunction, Right
PubMed: 33541611
DOI: 10.1016/j.ccm.2020.11.010 -
Archives of Cardiovascular Diseases Jan 2020Pulmonary arterial hypertension is a progressive and lethal cardiopulmonary disease. The rise in right ventricular afterload leads to right ventricular hypertrophy and... (Review)
Review
Pulmonary arterial hypertension is a progressive and lethal cardiopulmonary disease. The rise in right ventricular afterload leads to right ventricular hypertrophy and failure. Right ventricular failure is the most important prognostic factor for morbidity and mortality in pulmonary arterial hypertension or pulmonary hypertension caused by left heart diseases. Surprisingly, the right ventricle is not targeted by pulmonary arterial hypertension-specific therapies. The current profound lack of basic understanding of pulmonary arterial hypertension-related right ventricular remodelling can explain, at least in part, this paradox. The physiology and haemodynamic function of the right ventricle in the normal state differ considerably from those of the left ventricle, and the known mechanisms of left ventricular dysfunction cannot be generalized to right ventricular dysfunction. Ion channel activities and calcium homeostasis tightly regulate cardiac function, and their dysfunction contributes to the pathogenesis of cardiac diseases. This review focuses on the ion channels (potassium, calcium) and intracellular calcium handling remodelling involved in right ventricular hypertrophy and dysfunction caused by pulmonary arterial hypertension.
Topics: Action Potentials; Animals; Arterial Pressure; Calcium; Disease Models, Animal; Excitation Contraction Coupling; Heart Failure; Heart Rate; Heart Ventricles; Humans; Hypertrophy, Right Ventricular; Myocardial Contraction; Potassium; Prognosis; Pulmonary Arterial Hypertension; Pulmonary Artery; Risk Factors; Translational Research, Biomedical; Ventricular Dysfunction, Right; Ventricular Function, Right; Ventricular Remodeling
PubMed: 31924541
DOI: 10.1016/j.acvd.2019.10.009