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Journal of Cardiovascular Pharmacology May 2024This review summarizes the multiple roles of miRNAs in the prediction and treatment of heart failure (HF), including the molecular mechanisms regulating cell apoptosis,...
This review summarizes the multiple roles of miRNAs in the prediction and treatment of heart failure (HF), including the molecular mechanisms regulating cell apoptosis, myocardial fibrosis, cardiac hypertrophy and ventricular remodelling, and highlights the importance of miRNAs in the prognosis of HF. In addition, the strategies for alleviating HF with miRNA intervention are discussed. On the basis of the challenges and emerging directions in the research and clinical practice of HF miRNAs, it is proposed that miRNA-based therapy could be a new approach for prevention and treatment of HF.
PubMed: 38922572
DOI: 10.1097/FJC.0000000000001588 -
Arquivos Brasileiros de Cardiologia 2024Cardiomyopathy associated with partial lipodystrophy (PL) has not been well described yet.
BACKGROUND
Cardiomyopathy associated with partial lipodystrophy (PL) has not been well described yet.
OBJECTIVE
To characterize cardiac morphology and function in PL.
METHODS
Patients with familial PL and controls were prospectively assessed by transthoracic echocardiography and with speckle-tracking echocardiography (global longitudinal strain, GLS). The relationship between echocardiographic variables and PL diagnosis was tested with regression models, considering the effect of systolic blood pressure (SBP). Significance level of 5% was adopted.
RESULTS
Twenty-nine patients with PL were compared to 17 controls. They did not differ in age (p=0.94), gender or body mass index (p= 0.05). Patients with PL had statistically higher SBP (p=0.02) than controls. Also, PL patients had higher left atrial dimension (37.3 ± 4.4 vs. 32.1 ± 4.3 mm, p= 0.001) and left atrial (30.2 ± 7.2 vs. 24.9 ± 9.0 mL/m2,p=0.02), left ventricular (LV) mass (79.3 ± 17.4 vs. 67.1 ± 19.4, p=0.02), and reduced diastolic LV parameters (E' lateral, p= 0.001) (E' septal, p= 0.001), (E/E' ratio, p= 0.02). LV ejection fraction (64.7 ± 4.6 vs. 62.2 ± 4.4 %, p= 0.08) and GLS were not statistically different between groups (-17.1 ± 2.7 vs. -18.0 ± 2.0 %, p= 0.25). There was a positive relationship of left atrium (β 5.6, p<0.001), posterior wall thickness, (β 1.3, p=0.011), E' lateral (β -3.5, p=0.002) and E' septal (β -3.2, p<0.001) with PL diagnosis, even after adjusted for SBP.
CONCLUSION
LP patients have LV hypertrophy, left atrial enlargement, and LV diastolic dysfunction although preserved LVEF and GLS. Echocardiographic parameters are related to PL diagnosis independent of SBP.
Topics: Humans; Female; Male; Adult; Echocardiography; Case-Control Studies; Lipodystrophy, Familial Partial; Middle Aged; Prospective Studies; Blood Pressure; Heart Atria; Cardiomyopathies; Reference Values; Stroke Volume
PubMed: 38922260
DOI: 10.36660/abc.20230442 -
Frontiers in Cardiovascular Medicine 2024High blood pressure is a major risk factor for cardiac remodeling and left ventricular hypertrophy, increasing cardiovascular risk and leading to heart failure with...
BACKGROUND
High blood pressure is a major risk factor for cardiac remodeling and left ventricular hypertrophy, increasing cardiovascular risk and leading to heart failure with preserved ejection fraction (HFpEF). Since renal sympathetic denervation (RDN) reduces blood pressure in the long term, we aimed to investigate the long-term effect of RDN in patients with HFpEF in the present analysis.
METHODS
Patients previously enrolled in a local RDN registry who underwent high-frequency RDN with the use of the Symplicity Flex® renal denervation system between 2011 and 2014 were followed up. The patients were assessed by 24-h ambulatory blood pressure measurement, transthoracic echocardiography, and laboratory tests. We used the echocardiographic and biomarker criteria of the Heart Failure Association (HFA)-PEFF (Pre-test assessment, Echocardiography and Natriuretic Peptide Score, Funkctional testing, and Final aetiology) score to identify patients with HFpEF.
RESULTS
Echocardiographic assessment was available for 70 patients at a 9-year long-term follow-up. Of these patients, 21 had HFpEF according to the HFA-PEFF score. We found a significant reduction of the HFA-PEFF score from 5.48 ± 0.51 points at baseline to 4.33 ± 1.53 points at the 9-year follow-up ( < 0.01). This decrease was due to a greater reduction in morphological and biomarker subcategories [from 1.95 ± 0.22 to 1.43 ± 0.51 points ( < 0.01) and from 1.52 ± 0.52 to 0.90 ± 0.63 points ( < 0.01), respectively] than in the functional one. Morphologically, there was a reduction in left ventricular hypertrophy and left atrial dilation.
CONCLUSIONS
The present analysis suggests that RDN may lead to a regression of the extent of HFpEF beyond a reduction in blood pressure and thus possibly contribute to an improvement in prognosis. More detailed information will be provided by ongoing randomized sham-controlled trials.
PubMed: 38919545
DOI: 10.3389/fcvm.2024.1408547 -
BioRxiv : the Preprint Server For... Jun 2024Variability in physical resilience to aging prompts a comprehensive examination of underlying mechanisms across organs and individuals. We conducted a detailed...
Variability in physical resilience to aging prompts a comprehensive examination of underlying mechanisms across organs and individuals. We conducted a detailed exploration of behavioral and physiological differences between C57BL/6 and CB6F1 mice across various age groups. In behavioral assays, B6 mice displayed superior performance in rotarod tasks but higher anxiety while CB6F1 mice exhibited a decline in short-term memory with age. Grip strength, long-term memory, and voluntary wheel running declined similarly with age in both strains. Examining physiological phenotypes, B6 mice exhibited lower body fat percentages across ages compared to CB6F1 mice, though cataract severity worsened with age in both strains. Analysis of cardiac functions revealed differences between strains, with worsening left ventricular hypertrophy and structural heart abnormalities with age in CB6F1 mice along with higher blood pressure than B6. Lesion scores showed an age-related increase in heart, kidney, and liver lesions in both strains, while lung lesions worsened with age only in CB6F1 mice. This study underscores the validity of behavioral assays and geropathology assessment in reflecting age-related decline and emphasizes the importance of considering strain specificity when using mouse models to study human aging.
PubMed: 38915625
DOI: 10.1101/2024.06.14.599036 -
Respiratory Medicine Jun 2024Pulmonary hypertension (PH) is the abnormal elevation of pressure in the pulmonary vascular system, with various underlying causes. A specific type of PH is pulmonary...
BACKGROUND
Pulmonary hypertension (PH) is the abnormal elevation of pressure in the pulmonary vascular system, with various underlying causes. A specific type of PH is pulmonary arterial hypertension (PAH), a severe condition characterized by high pulmonary arterial pressure resulting from structural changes in distal pulmonary vessels, altered arterial tone, and inflammation. This leads to right ventricular hypertrophy and heart failure. The molecular mechanisms behind PAH are not well understood. This manuscript aims to elucidate these mechanisms using the genetic tool, aiding in diagnosis and treatment selection.
METHOD
In our present study, we have obtained blood samples from both patients with pulmonary arterial hypertension (PAH) and healthy individuals. We conducted a comparative transcriptome analysis to identify genes that are either upregulated or downregulated in PAH patients when compared to the control group. Subsequently, we carried out a validation study focusing on the log2-fold downregulated genes in PAH, employing Quantitative Real-Time PCR for confirmation. Additionally, we quantified the proteins encoded by the validated genes using the ELISA technique.
RESULTS
The results of the transcriptome analysis revealed that 97 genes were significantly upregulated, and 6 genes were significantly downregulated. Among these, we chose to focus on and validate only four of the downregulated genes, as they were directly or indirectly associated with the hypertension pathway. We also conducted validation studies for the proteins encoded by these genes, and the results were consistent with those obtained in the transcriptome analysis.
CONCLUSION
In conclusion, the findings of this study indicate that the four validated genes identified in the context of PAH can be further explored as potential targets for both diagnostic and therapeutic applications.
PubMed: 38914209
DOI: 10.1016/j.rmed.2024.107716 -
European Heart Journal. Cardiovascular... Jun 2024To evaluate different cardiovascular magnetic resonance (CMR) parameters for the differentiation of light chain amyloidosis (AL) and transthyretin-related amyloidosis...
AIMS
To evaluate different cardiovascular magnetic resonance (CMR) parameters for the differentiation of light chain amyloidosis (AL) and transthyretin-related amyloidosis (ATTR).
METHODS AND RESULTS
In total, 75 patients, 53 with cardiac amyloidosis (20 patients with AL (66±12 years, 14 males [70%]) and 33 patients with ATTR (78±5 years, 28 males [88%])) were retrospectively analyzed regarding CMR parameters such as T1 and T2 mapping, extracellular volume (ECV), and late gadolinium enhancement (LGE) distribution patterns, and myocardial strain, and compared to a control cohort with other causes of left ventricular hypertrophy (LVH; 22 patients (53±16 years, 17 males [85%])). One way-ANOVA and receiver operating characteristic analysis were used for statistical analysis. ECV was the single best parameter to differentiate between cardiac amyloidosis and controls (area under the curve [AUC]: 0.97, 95% confidence intervals [CI]: 0.89-0.99, p<.0001, cutoff: >30%). T2 mapping was the best single parameter to differentiate between AL and ATTR amyloidosis (AL: 63±4 ms, ATTR: 58±2 ms, p<.001, AUC: 0.86, 95% CI: 0.74-0.94, cutoff: >61 ms). Subendocardial LGE was predominantly observed in AL patients (10/20 [50%] vs. 5/33 [15%]; p=.002). Transmural LGE was predominantly observed in ATTR patients (23/33 [70%] vs. 2/20 [10%]; p<.001). The diagnostic performance of T2 mapping to differentiate between AL and ATTR amyloidosis was further increased with the inclusion of LGE patterns (AUC: 0.96, 95% CI: 0.86-0.99]; p=.05).
CONCLUSION
ECV differentiates cardiac amyloidosis from other causes of LVH. T2 mapping combined with LGE differentiates AL from ATTR amyloidosis with high accuracy on a patient level.
PubMed: 38912832
DOI: 10.1093/ehjci/jeae154 -
Molecular Genetics and Metabolism... Sep 2024The detailed clinical phenotype of patients carrying the α-galactosidase gene () / () variant in Fabry disease (FD) has not been thoroughly documented in the...
BACKGROUND
The detailed clinical phenotype of patients carrying the α-galactosidase gene () / () variant in Fabry disease (FD) has not been thoroughly documented in the existing literature.
METHODS
This paper offers a meticulous overview of the clinical phenotype and relevant auxiliary examination results of nine confirmed FD patients with the gene variant from two families. Pedigree analysis was conducted on two male patients with the gene variant, followed by biochemical and genetic screening of all high-risk relatives. Subsequently, evaluation of multiple organ systems and comprehensive instrument assessment were performed on heterozygotes of the gene variant.
RESULTS
The study revealed that all patients exhibited varying degrees of cardiac involvement, with two demonstrating left ventricular wall thickness exceeding 15 mm on echocardiography, and the remaining six exceeding 11 mm. Impaired renal function was evident in all six patients with available blood test data, two of whom underwent kidney transplantation. Eight cases reported neuropathic pain, and five experienced varying degrees of stroke or transient ischemic attack (TIA).
CONCLUSION
This study indicates that the gene variant can induce premature organ damage, particularly affecting the heart, kidneys, and nervous system.
PubMed: 38911695
DOI: 10.1016/j.ymgmr.2024.101102 -
Frontiers in Cardiovascular Medicine 2024Little is known about left ventricular (LV) sequences of contraction and electrical activation in hypertrophic cardiomyopathy (HCM). A better understanding of the...
BACKGROUND
Little is known about left ventricular (LV) sequences of contraction and electrical activation in hypertrophic cardiomyopathy (HCM). A better understanding of the underlying relation between mechanical and electrical activation may allow the identification of predictive response criteria to right ventricular DDD pacing in obstructive patients.
OBJECTIVE
To describe LV mechanical and electrical activation sequences in HCM patients compared to controls.
MATERIALS AND METHODS
We prospectively studied, in 40 HCM patients (20 obstructive and 20 non-obstructive) and 20 healthy controls: (1) mechanical activation using echocardiography at rest and cardiac magnetic resonance imaging, (2) electrical activation using 3-dimensional electrocardiographic mapping (ECM).
RESULTS
In echocardiography, healthy controls had a physiological apex-to-base delay (ABD) during contraction (23.8 ± 16.2 ms). Among the 40 HCM patients, 18 HCM patients presented a loss of this ABD (<10 ms, defining hypersynchrony) more frequently than controls (45% vs. 5%, = 0.017). These patients had a lower LV end-diastolic volume (71.4 ± 9.7 ml/m vs. 82.4 ± 14.8 ml/m, = 0.01), lower native T1 values (988 ± 32 ms vs. 1,028 ± 39 ms, = 0.001) and tended to have lower LV mass (80.7 ± 23.7 g/m vs. 94.5 ± 25.3 g/m, = 0.08) compared with HCM patients that had a physiological contraction sequence. There was no significant relation between ABD and LV outflow tract obstruction. While HCM patients with a physiological contraction sequence presented an ECM close to those encountered in controls, patients with a loss of ABD presented a particular pattern of ECM with the first potential more frequently occurring in the postero-basal region.
CONCLUSION
The LV contraction sequence can be modified in HCM patients, with a loss of the physiological ABD, and is associated with smaller LV dimensions and a particular pattern of ECM. Further research is needed to determine whether this pattern is related to an electrical substrate or is the consequence of the hypertrophied heart's specific geometry.
CLINICAL TRIAL REGISTRATION
ClinicalTrial.gov: NCT02559726.
PubMed: 38911519
DOI: 10.3389/fcvm.2024.1359657 -
Proceedings (Baylor University. Medical... 2024We conducted a comprehensive systematic review to examine the efficacy of intensive blood pressure lowering on the risk of left ventricular hypertrophy (LVH).
The effect of intensive blood pressure lowering on left ventricular hypertrophy in patients with hypertension: a systematic review and meta-analysis of randomized controlled trials.
BACKGROUND
We conducted a comprehensive systematic review to examine the efficacy of intensive blood pressure lowering on the risk of left ventricular hypertrophy (LVH).
METHODS
We searched PubMed, Scopus, Web of Science, Cochrane Central, and EMBASE for all relevant randomized controlled trials. The primary outcome was the incidence of left ventricular hypertrophy. We used the risk ratio (RR) and hazard ratio (HR) with a 95% confidence interval as our effect sizes.
RESULTS
Four studies, comprising 20,747 patients, were included. Intensive blood pressure lowering was linked with a diminished LVH incidence (RR: 0.66, 95% CI [0.56-0.77]). We also found that intensive blood pressure lowering increased the risk of LVH regression in patients with baseline LVH (RR: 1.21, 95% CI [1.11-1.32]). Finally, intensive blood pressure lowering was linked with a reduced risk of cardiovascular disease (HR: 0.71, 95% CI [0.60-0.85]). No significant heterogeneity was seen in either outcome.
CONCLUSION
Our study suggests that intensive blood pressure lowering effectively reduces the risk of LVH and cardiovascular disease. An interactive version of our analysis can be accessed here: https://databoard.shinyapps.io/lvh_hypertophy/.
PubMed: 38910799
DOI: 10.1080/08998280.2024.2346409 -
Circulation. Genomic and Precision... Jun 2024Genetic hypertrophic cardiomyopathy (HCM) is classically caused by pathogenic/likely pathogenic variants in sarcomere genes (G+). Currently, HCM is diagnosed if there is... (Review)
Review
Genetic hypertrophic cardiomyopathy (HCM) is classically caused by pathogenic/likely pathogenic variants in sarcomere genes (G+). Currently, HCM is diagnosed if there is unexplained left ventricular (LV) hypertrophy with LV wall thickness ≥15 mm in probands or ≥13 mm in at-risk relatives. Although LV hypertrophy is a key feature, this binary metric does not encompass the full constellation of phenotypic features, particularly in the subclinical stage of the disease. Subtle phenotypic manifestations can be identified in sarcomere variant carriers with normal LV wall thickness, before diagnosis with HCM (G+/LV hypertrophy-; subclinical HCM). We conducted a systematic review to summarize current knowledge about the phenotypic spectrum of subclinical HCM and factors influencing penetrance and expressivity. Although the mechanisms driving the development of LV hypertrophy are yet to be elucidated, activation of profibrotic pathways, impaired relaxation, abnormal Ca signaling, altered myocardial energetics, and microvascular dysfunction have all been identified in subclinical HCM. Progression from subclinical to clinically overt HCM may be more likely if early phenotypic manifestations are present, including abnormal ECG, longer mitral valve leaflets, lower global E' velocities on Doppler echocardiography, and higher serum N-terminal propeptide of B-type natriuretic peptide. Longitudinal studies of variant carriers are critically needed to improve our understanding of penetrance, characterize the transition to disease, identify risk predictors of phenotypic evolution, and guide the development of novel treatment strategies aimed at influencing disease trajectory.
PubMed: 38910555
DOI: 10.1161/CIRCGEN.124.004580