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Life Sciences Jan 2024Cardiac hypertrophy and fibrosis are associated with cardiac remodeling and heart failure. We have previously shown that miRNA-217, embedded within the third intron of...
AIM
Cardiac hypertrophy and fibrosis are associated with cardiac remodeling and heart failure. We have previously shown that miRNA-217, embedded within the third intron of MIR217HG, aggravates pressure overload-induced cardiac hypertrophy by targeting phosphatase and tensin homolog. However, whether the MIR217HG transcript itself plays a role in cardiac remodeling remains unknown.
METHODS
Real-time PCR assays and RNA in situ hybridization were performed to detect MIR217HG expression. Lentiviruses and adeno-associated viruses with a cardiac-specific promoter (cTnT) were used to control MIR217HG expression in vitro and in vivo. Transverse aortic constriction (TAC) surgery was performed to develop cardiac remodeling models. Cardiac structure and function were analyzed using echocardiography and invasive pressure-volume analysis.
KEY FINDINGS
MIR217HG expression was increased in patients with heart failure. MIR217HG overexpression aggravated pressure-overload-induced myocyte hypertrophy and fibrosis both in vivo and in vitro, whereas MIR217HG knockdown reversed these phenotypes. Mechanistically, MIR217HG increased THBS1 expression by sponging miR-138. MiR-138 recognized the 3'UTR of THBS1 and repressed THBS1 expression in the absence of MIR217HG. Silencing THBS1 expression reversed MIR217HG-induced cardiac hypertrophy and remodeling.
CONCLUSION
MIR217HG acts as a potent inducer of cardiac remodeling that may contribute to heart failure by activating the miR-138/THBS1 pathway.
Topics: Humans; Animals; Mice; RNA, Long Noncoding; Ventricular Remodeling; Cardiomegaly; Heart Failure; MicroRNAs; Fibrosis; Myocytes, Cardiac; Mice, Inbred C57BL
PubMed: 38013141
DOI: 10.1016/j.lfs.2023.122290 -
Journal of Clinical Medicine Jul 2023Wild-type transthyretin amyloid cardiomyopathy (wtATTR-CM) is characterized by heart failure, conduction abnormalities and arrhythmias. The incidence of ventricular...
BACKGROUND
Wild-type transthyretin amyloid cardiomyopathy (wtATTR-CM) is characterized by heart failure, conduction abnormalities and arrhythmias. The incidence of ventricular arrhythmias, particularly ventricular tachycardias (VTs), in wtATTR-CM is unclear. With the development of targeted therapies and improved overall prognosis, there is an unmet need to identify patients at high risk for VTs who might benefit from ICD therapy.
METHODS
Between 2017 and 2022, 72 patients diagnosed with wtATTR-CM were prospectively evaluated for the presence of ventricular arrhythmias using a Holter ECG. VTs were defined as >3 consecutive beats with a heart rate > 100 beats per minute originating from a ventricle.
RESULTS
The incidence of VTs was 44% (n = 32/72) in unselected wtATTR-CM patients. Patients with VT showed significantly more severe left ventricular (LV) hypertrophy (septum diameter 21 ± 2.6 vs. 19 ± 3.0 mm, = 0.006), reduced LV ejection fraction (47 ± 8 vs. 52 ± 8%, = 0.014) and larger left atria (32 ± 7 vs. 28 ± 6 mm, = 0.020), but no differences in cardiac markers such as NTproBNP and troponin. In a multivariable model, LV hypertrophy (LV mass indexed, OR = 1.02 [1.00-1.03], = 0.031), LV end-diastolic diameter (OR = 0.85 [0.74-0.98], = 0.021) and LV end-systolic diameter (OR = 1.19 [1.03-1.349], = 0.092) were predictive for VT occurrence with an area under the receiver operating characteristic of 0.76 [0.65-0.87].
CONCLUSIONS
The incidence of ventricular arrhythmia in wtATTR-CM is high and is associated with an advanced stage of left ventricular disease. Further studies are needed evaluating the role of VTs in predicting sudden cardiac death and the benefit of ICD therapy in wtATTR-CM.
PubMed: 37510739
DOI: 10.3390/jcm12144624 -
Medicina (Kaunas, Lithuania) Aug 2023Hypertrophic cardiomyopathy (HCM) is the most prevalent heritable cardiomyopathy. HCM is considered to be caused by mutations in cardiac sarcomeric protein genes. Recent... (Review)
Review
Hypertrophic cardiomyopathy (HCM) is the most prevalent heritable cardiomyopathy. HCM is considered to be caused by mutations in cardiac sarcomeric protein genes. Recent research suggests that the genetic foundation of HCM is much more complex than originally postulated. The clinical presentations of HCM are very variable. Some mutation carriers remain asymptomatic, while others develop severe HCM, terminal heart failure, or sudden cardiac death. Heterogeneity regarding both genetic mutations and the clinical course of HCM hinders the establishment of universal genotype-phenotype correlations. However, some trends have been identified. The presence of a mutation in some genes encoding sarcomeric proteins is associated with earlier HCM onset, more severe left ventricular hypertrophy, and worse clinical outcomes. There is a diversity in the mechanisms implicated in the pathogenesis of HCM. They may be classified into groups, but they are interrelated. The lack of known supplementary elements that control the progression of HCM indicates that molecular mechanisms that exist between genotype and clinical presentations may be crucial. Secondary molecular changes in pathways implicated in HCM pathogenesis, post-translational protein modifications, and epigenetic factors affect HCM phenotypes. Cardiac loading conditions, exercise, hypertension, diet, alcohol consumption, microbial infection, obstructive sleep apnea, obesity, and environmental factors are non-molecular aspects that change the HCM phenotype. Many mechanisms are implicated in the course of HCM. They are mostly interconnected and contribute to some extent to final outcomes.
Topics: Humans; Cardiomyopathy, Hypertrophic; Heart; Heart Diseases; Hypertrophy, Left Ventricular; Alcohol Drinking
PubMed: 37629714
DOI: 10.3390/medicina59081424 -
Kidney360 Aug 2023Higher plasma and urine kidney injury molecule-1, urine monocyte chemoattractant protein-1, and lower urine alpha-1-microglobulin were associated with left ventricular...
KEY POINTS
Higher plasma and urine kidney injury molecule-1, urine monocyte chemoattractant protein-1, and lower urine alpha-1-microglobulin were associated with left ventricular hypertrophy, even after adjustment for confounders. Biomarkers of tubular injury, dysfunction, and inflammation may indicate the severity of kidney pathology and are associated with left ventricular hypertrophy.
BACKGROUND
Left ventricular hypertrophy (LVH) is common in children with CKD and is associated with an increased risk of cardiovascular disease and mortality. We have shown that several plasma and urine biomarkers are associated with increased risk of CKD progression. As CKD is associated with LVH, we sought to investigate the association between the biomarkers and LVH.
METHODS
In the CKD in Children Cohort Study, children aged 6 months to 16 years with an eGFR of 30–90 ml/min per 1.73 m were enrolled at 54 centers in the United States and Canada. We measured plasma biomarkers kidney injury molecule-1 (KIM-1), tumor necrosis factor receptor-1, tumor necrosis factor receptor-2, soluble urokinase-type plasminogen activator receptor and urine KIM-1, monocyte chemoattractant protein-1 (MCP-1), YKL-40, alpha-1-microglobulin (alpha-1m), and epidermal growth factor in stored plasma and urine collected 5 months after enrollment. Echocardiograms were performed 1 year after enrollment. We assessed the cross-sectional association between the log biomarker levels and LVH (left ventricular mass index greater than or equal to the 95th percentile) using a Poisson regression model, adjusted for age, sex, race, body mass index, hypertension, glomerular diagnosis, urine protein-to-creatinine ratio, and eGFR at study entry.
RESULTS
Among the 504 children, LVH prevalence was 12% (=59) 1 year after enrollment. In a multivariable-adjusted model, higher plasma and urine KIM-1 and urine MCP-1 concentrations were associated with a higher prevalence of LVH (plasma KIM-1 prevalence ratio [PR] per log: 1.27, 95% confidence interval [CI], 1.02 to 1.58; urine KIM-1 PR: 1.21, 95% CI, 1.11 to 1.48; and urine MCP-1 PR: 1.18, 95% CI, 1.04 to 1.34). After multivariable adjustment for covariates, lower urine alpha-1m was also associated with a higher prevalence of LVH (PR: 0.90, 95% CI, 0.82 to 0.99).
CONCLUSIONS
Higher plasma and urine KIM-1, urine MCP-1, and lower urine alpha-1m were each associated with LVH prevalence in children with CKD. These biomarkers may better inform risk and help elucidate the pathophysiology of LVH in pediatric CKD.
Topics: Humans; Child; Hypertrophy, Left Ventricular; Inflammation; Renal Insufficiency, Chronic; Kidney Tubules; Biomarkers
PubMed: 37303083
DOI: 10.34067/KID.0000000000000183 -
JACC. Asia Oct 2023
PubMed: 38094993
DOI: 10.1016/j.jacasi.2023.07.001 -
European Heart Journal. Cardiovascular... Sep 2023To describe hypertension-related cardiovascular magnetic resonance (CMR) phenotypes in the UK Biobank considering variations across patient populations.
AIMS
To describe hypertension-related cardiovascular magnetic resonance (CMR) phenotypes in the UK Biobank considering variations across patient populations.
METHODS AND RESULTS
We studied 39 095 (51.5% women, mean age: 63.9 ± 7.7 years, 38.6% hypertensive) participants with CMR data available. Hypertension status was ascertained through health record linkage. Associations between hypertension and CMR metrics were estimated using multivariable linear regression adjusting for major vascular risk factors. Stratified analyses were performed by sex, ethnicity, time since hypertension diagnosis, and blood pressure (BP) control. Results are standardized beta coefficients, 95% confidence intervals, and P-values corrected for multiple testing. Hypertension was associated with concentric left ventricular (LV) hypertrophy (increased LV mass, wall thickness, concentricity index), poorer LV function (lower global function index, worse global longitudinal strain), larger left atrial (LA) volumes, lower LA ejection fraction, and lower aortic distensibility. Hypertension was linked to significantly lower myocardial native T1 and increased LV ejection fraction. Women had greater hypertension-related reduction in aortic compliance than men. The degree of hypertension-related LV hypertrophy was greatest in Black ethnicities. Increasing time since diagnosis of hypertension was linked to adverse remodelling. Hypertension-related remodelling was substantially attenuated in hypertensives with good BP control.
CONCLUSION
Hypertension was associated with concentric LV hypertrophy, reduced LV function, dilated poorer functioning LA, and reduced aortic compliance. Whilst the overall pattern of remodelling was consistent across populations, women had greater hypertension-related reduction in aortic compliance and Black ethnicities showed the greatest LV mass increase. Importantly, adverse cardiovascular remodelling was markedly attenuated in hypertensives with good BP control.
Topics: Male; Humans; Female; Middle Aged; Aged; Biological Specimen Banks; Hypertension; Hypertrophy, Left Ventricular; Ventricular Function, Left; Heart Atria; Phenotype; United Kingdom
PubMed: 37309807
DOI: 10.1093/ehjci/jead123 -
Stromal Cell-SLIT3/Cardiomyocyte-ROBO1 Axis Regulates Pressure Overload-Induced Cardiac Hypertrophy.Circulation Research Mar 2024Recently shown to regulate cardiac development, the secreted axon guidance molecule SLIT3 maintains its expression in the postnatal heart. Despite its known expression...
BACKGROUND
Recently shown to regulate cardiac development, the secreted axon guidance molecule SLIT3 maintains its expression in the postnatal heart. Despite its known expression in the cardiovascular system after birth, SLIT3's relevance to cardiovascular function in the postnatal state remains unknown. As such, the objectives of this study were to determine the postnatal myocardial sources of SLIT3 and to evaluate its functional role in regulating the cardiac response to pressure overload stress.
METHODS
We performed in vitro studies on cardiomyocytes and myocardial tissue samples from patients and performed in vivo investigation with SLIT3 and ROBO1 (roundabout homolog 1) mutant mice undergoing transverse aortic constriction to establish the role of SLIT3-ROBO1 in adverse cardiac remodeling.
RESULTS
We first found that transcription was increased in myocardial tissue obtained from patients with congenital heart defects that caused ventricular pressure overload. Immunostaining of hearts from WT (wild-type) and reporter mice revealed that SLIT3 is secreted by cardiac stromal cells, namely fibroblasts and vascular mural cells, within the heart. Conditioned media from cardiac fibroblasts and vascular mural cells both stimulated cardiomyocyte hypertrophy in vitro, an effect that was partially inhibited by an anti-SLIT3 antibody. Also, the N-terminal, but not the C-terminal, fragment of SLIT3 and the forced overexpression of stimulated cardiomyocyte hypertrophy and the transcription of hypertrophy-related genes. We next determined that ROBO1 was the most highly expressed roundabout receptor in cardiomyocytes and that ROBO1 mediated SLIT3's hypertrophic effects in vitro. In vivo, Tcf21+ fibroblast and Tbx18+ vascular mural cell-specific knockout of SLIT3 in mice resulted in decreased left ventricular hypertrophy and cardiac fibrosis after transverse aortic constriction. Furthermore, α-MHC+ cardiomyocyte-specific deletion of ROBO1 also preserved left ventricular function and abrogated hypertrophy, but not fibrosis, after transverse aortic constriction.
CONCLUSIONS
Collectively, these results indicate a novel role for the SLIT3-ROBO1-signaling axis in regulating postnatal cardiomyocyte hypertrophy induced by pressure overload.
Topics: Animals; Humans; Mice; Cardiomegaly; Cells, Cultured; Disease Models, Animal; Fibrosis; Hypertrophy, Left Ventricular; Membrane Proteins; Mice, Inbred C57BL; Mice, Knockout; Myocytes, Cardiac; Nerve Tissue Proteins; Receptors, Immunologic; Ventricular Remodeling
PubMed: 38414132
DOI: 10.1161/CIRCRESAHA.122.321292 -
Maedica Dec 2023Severe aortic stenosis is often associated with left ventricular hypertrophy (LVH). Elevated left ventricular mass (LVM) is linked to higher cardiovascular morbidity...
Comparative Analysis of Left Ventricular Mass Regression Following Transcatheter Aortic Valve Implantation and Surgical Aortic Valve Replacement - a Single Center Experience from Romania.
Severe aortic stenosis is often associated with left ventricular hypertrophy (LVH). Elevated left ventricular mass (LVM) is linked to higher cardiovascular morbidity and mortality. Traditionally, surgical aortic valve replacement (SAVR) has been the standard treatment, but transcatheter aortic valve implantation (TAVI) offers an alternative for high-risk surgical patients. Understanding how these interventions affect left ventricular mass regression is crucial. This retrospective study analyzed 315 patients treated between December 2014 and December 2022, categorizing them into surgical and transcatheter treatment groups. Clinical and echocardiographic data were collected at baseline and six-month follow-up. Statistical analysis assessed differences between groups and predictors of LV mass reduction. The overall dataset indicated an average percentage reduction in LVM of 10.86%±29.41%. Segmenting the data, the TAVI subgroup exhibited a reduction of 4.28%±30.31%, while the SAVR subgroup highlighted a pronounced decline of 17.92%±26.76%. Preoperative LVMi and mean pressure gradient positively correlated with LVM reduction, while TAVI negatively impacted it. Both TAVI and SAVR interventions yield benefits in reducing left ventricular mass, with SAVR showing a superior outcome. Recognizing predictors of LV mass regression is crucial for optimizing treatment strategies, and early valve replacement should be considered to prevent irreversible LV hypertrophy.
PubMed: 38348071
DOI: 10.26574/maedica.2023.18.4.555 -
Journal of Clinical Medicine Aug 2023This review aims to serve as a guide for clinical practice and to appraise the current knowledge on exercise stress echocardiography in the evaluation of... (Review)
Review
This review aims to serve as a guide for clinical practice and to appraise the current knowledge on exercise stress echocardiography in the evaluation of intraventricular obstruction in HCM, in patients with cardiac syndrome X, in athletes with symptoms related to exercise, and in patients with normal left ventricular systolic function and exercise-related unexplained tiredness. The appearance of intraventricular obstruction while exercising is considered rare, and it usually occurs in patients with hypertrophy of the left ventricle. The occurrence of intraventricular obstruction when exercising has been evidenced in patients with hypertrophic cardiomyopathy, athletes, patients with cardiac syndrome X, patients with syncope or dizziness related to exercise, and patients with dyspnea and preserved ejection fraction. The clinical significance of this observation and the exercise modality that is most likely to trigger intraventricular obstruction remains unknown. Supine exercise and lying supine after exercise are less technically demanding, but they are also less physiologically demanding than upright exercise. Importantly, in everyday life, human beings generally do not become supine after exercise, as takes place in post-exercise treadmill stress echocardiograms in most echocardiography labs. The presence of induced intraventricular obstruction might be considered when patients have exercise-related symptoms that are not understood, and to assess prognosis in hypertrophic cardiomyopathy.
PubMed: 37629333
DOI: 10.3390/jcm12165292 -
CJC Open Dec 2023Electrocardiographic (ECG) criteria to detect left ventricular hypertrophy (LVH) in patients with left bundle branch block (LBBB) remain under debate. We conducted a... (Review)
Review
BACKGROUND
Electrocardiographic (ECG) criteria to detect left ventricular hypertrophy (LVH) in patients with left bundle branch block (LBBB) remain under debate. We conducted a systematic review and meta-analysis to evaluate the diagnostic accuracy of different ECG criteria for diagnosing LVH in patients with LBBB.
METHODS
We searched PubMed, Embase, Cochrane, and LILACS for articles evaluating the diagnostic accuracy of ECG criteria for LVH in patients with LBBB published between 1984 and 2023. Echocardiogram, magnetic resonance imaging, or autopsy were used as the reference standard for diagnosis of LVH. Risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. The co-primary outcomes were sensitivity, specificity, the diagnostic odds ratio, and likelihood ratios, estimated using a bivariate generalized linear mixed model for each ECG criterion. The prespecified protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO).
RESULTS
We included 12 studies with a total of 1023 patients. We analyzed 10 criteria for LVH on ECG, including the Sokolow-Lyon criterion, the Cornell criterion, the RaVL (R wave in aVL) criterion, the Gubner-Ungerleider criterion, and the Dálfo criterion, among others. The Dalfó criterion was used for 487 patients and had the highest pooled sensitivity of 86% (95% confidence interval [CI] 57%-97%). All the other criteria had poor sensitivities. The Gubner-Ungerleider criterion and the RV5 or RV6 > 25 mm criterion had the highest specificities, with the former being used for 805 patients, obtaining a specificity of 99% (95% CI 80%-100%) and the latter being used for 355 patients, obtaining a specificity of 99% (95% CI 94%-100%).
CONCLUSIONS
In patients with LBBB, the use of ECG criteria had poor performance for ruling out LVH, mostly due to low sensitivities. None of the criteria analyzed demonstrated a balanced tradeoff between sensitivity and specificity, suggesting that ECG should not be used routinely to screen for LVH.
PubMed: 38204852
DOI: 10.1016/j.cjco.2023.08.010