scholarly journals CMR-Verified Myocardial Fibrosis is Associated With Subclinical Diastolic Dysfunction in Primary Aldosteronism Patients

2021 ◽  
Author(s):  
Fangli Zhou ◽  
Tao Wu ◽  
Wei Wang ◽  
Wei Cheng ◽  
Shuang Wan ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Essential Hypertension ◽  
Diastolic Dysfunction ◽  
Myocardial Fibrosis ◽  
Primary Aldosteronism ◽  
Cardiac Fibrosis ◽  
Final Analysis ◽  
Left Ventricular ◽  
Diffuse Myocardial Fibrosis ◽  
Plasma Aldosterone Concentration

Abstract The main cardiac features of primary aldosteronism (PA) are impaired left ventricular (LV) diastolic function, and some articles also reported more cardiac fibrosis in PA patients. However, the correlation between LV dysfunction and diffuse myocardial fibrosis in PA remains unknown. We enrolled 84 PA patients and 28 essential hypertension (EH) patients in West China Hospital. Cardiac magnetic resonance imaging (CMR) contrast enhancement was arranged for all subjects. Postcontrast T1 time and left ventricular myocardial strains and strain rates were measured. 76 PA patients and 27 essential hypertension (EH) patients were included in the final analysis. Blood pressure, LV mass indexes, and LV ejection fractions were comparable in both groups, while the global circumferential peak diastolic strain rate (PDSR) was lower (53 ± 20 vs. 68 ± 25, p<0.01) and the postcontrast T1 time was shorter (520 ± 38 vs. 538 ± 27, p=0.01) in PA patients than those in EH patients. Postcontrast T1 time (p=0.01) was independently related to global circumferential PDSR after adjusting for age and duration of hypertension in PA patients. Furthermore, plasma aldosterone concentration was negatively associated with myocardial T1 time (R=-0.261, p=0.023) in PA patients. The global circumferential PDSR derived by CMR is decreased, and the diffuse myocardial fibrosis is increased in PA patients compared to those in blood pressure matched EH patients. The severity of cardiac diastolic dysfunction independently relates to the degree of diffuse myocardial fibrosis in PA patients, and the diffuse myocardial fibrosis may be caused by high PAC level. Trial registration number: ChiCTR2000031792.

scholarly journals CMR-Verified Myocardial Fibrosis Is Associated With Subclinical Diastolic Dysfunction in Primary Aldosteronism Patients

2021 ◽  
Vol 12 ◽  
Author(s):  
Fangli Zhou ◽  
Tao Wu ◽  
Wei Wang ◽  
Wei Cheng ◽  
Shuang Wan ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Essential Hypertension ◽  
Diastolic Dysfunction ◽  
Myocardial Fibrosis ◽  
Primary Aldosteronism ◽  
Cardiac Fibrosis ◽  
Left Ventricular ◽  
Diffuse Myocardial Fibrosis ◽  
Clinical Trial Registration ◽  
Plasma Aldosterone Concentration

ObjectivesThe main cardiac features of primary aldosteronism (PA) are impaired left ventricular (LV) diastolic function, and some articles also reported more cardiac fibrosis in PA patients. However, the correlation between LV dysfunction and diffuse myocardial fibrosis in PA remains unknown.MethodsWe enrolled 84 PA patients and 28 essential hypertension (EH) patients in West China Hospital. Cardiac magnetic resonance imaging (CMR) contrast enhancement was arranged for all subjects. Postcontrast T1 time and left ventricular myocardial strains and strain rates were measured.Results76 PA patients and 27 essential hypertension (EH) patients were included in the final analysis. Blood pressure, LV mass indexes, and LV ejection fractions were comparable in both groups, while the global circumferential peak diastolic strain rate (PDSR) was lower (0.9 ± 0.3 vs. 1.1 ± 0.4, p &lt;0.01) and the postcontrast T1 time was shorter (520 ± 38 vs. 538 ± 27, p = 0.01) in PA patients than those in EH patients. Postcontrast T1 time (p = 0.01) was independently related to global circumferential PDSR after adjusting for age and duration of hypertension in PA patients. Furthermore, plasma aldosterone concentration was negatively associated with postcontrast T1 time (R = −0.253, p = 0.028) in PA patients.ConclusionsThe global circumferential PDSR derived by CMR is decreased, and the diffuse myocardial fibrosis is increased in PA patients compared to those in blood pressure matched EH patients. The severity of cardiac diastolic dysfunction independently relates to the degree of diffuse myocardial fibrosis in PA patients, and the diffuse myocardial fibrosis may be caused by high PAC level.Clinical Trial Registrationhttp://www.chictr.org.cn/listbycreater.asp, identifier ChiCTR2000031792.

scholarly journals Hemodynamic and Non-Hemodynamic Components of Cardiac Remodeling in Primary Aldosteronism

2021 ◽  
Vol 12 ◽  
Author(s):  
Chien-Ting Pan ◽  
Xue-Ming Wu ◽  
Cheng-Hsuan Tsai ◽  
Yi-Yao Chang ◽  
Zheng-Wei Chen ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Multivariate Analysis ◽  
Cardiac Remodeling ◽  
Primary Aldosteronism ◽  
Left Ventricular Mass Index ◽  
Left Ventricular ◽  
Plasma Aldosterone Concentration ◽  
Lv Remodeling ◽  
Aldosterone Producing Adenoma ◽  
Aldosterone To Renin Ratio

ObjectivesPatients with primary aldosteronism (PA) have cardiac remodeling due to hemodynamic and non-hemodynamic causes. However, component analysis of cardiac remodeling and reversal in PA patients is lacking. We investigated components of cardiac remodeling and reversal after adrenalectomy in patients with aldosterone-producing adenoma (APA).MethodsThis study prospectively enrolled 304 APA patients who received adrenalectomy and 271 with essential hypertension (EH). Clinical, biochemical and echocardiographic data were collected in both groups and 1 year after surgery in the APA patients. The hemodynamic and non-hemodynamic components of left ventricular (LV) remodeling were represented by predicted left ventricular mass index (LVMI) (pLVMI) and inappropriately excessive LVMI (ieLVMI, defined as LVMI-pLVMI).ResultsAfter propensity score matching, 213 APA and 213 EH patients were selected. APA patients had higher hemodynamic (pLVMI) and non-hemodynamic (ieLVMI) components of LV remodeling than EH patients. In multivariate analysis, baseline pLVMI was correlated with systolic blood pressure (SBP) and serum potassium, whereas ieLVMI was correlated with log plasma aldosterone concentration but not blood pressure. Post-operative echocardiography was available in 207 patents and showed significant decreases in both pLVMI and ieLVMI after adrenalectomy. In multivariate analysis, ΔpLVMI was correlated with SBP, ΔSBP, and pre-operative pLVMI, whereas ΔieLVMI was correlated with Δlog aldosterone-to-renin ratio (ARR) and pre-operative ieLVMI.ConclusionsThis study concluded that extensive cardiac remodeling in APA patients occurs through hemodynamic and non-hemodynamic causes. Adrenalectomy can improve both hemodynamic and non-hemodynamic components of LV remodeling. Regressions of pLVMI and ieLVMI were correlated with decreases in blood pressure and ARR, respectively.

scholarly journals MON-213 Cardiac Damage and Related Risk Factors in Patients with Primary Aldosteronism

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
wei wang
Keyword(s):  
Risk Factors ◽  
Blood Pressure ◽  
Essential Hypertension ◽  
Primary Aldosteronism ◽  
Potassium Level ◽  
Serum Potassium Level ◽  
Left Ventricular ◽  
Cardiac Damage ◽  
Course Of Disease ◽  
Related Risk

Abstract Primary aldosteronism (PA) is the most common cause of secondary hypertension. Overseas flow surveys show that compared with essential hypertension (EH), the risk of cardiovascular and cerebrovascular diseases and kidney damages in PA patients is increased, and the mortality rate of cardiovascular events is higher than that in EH patients, in addition,this effect is independent of elevated blood pressure. The difference of cardiac damage between PA and EH patients was analyzed by echocardiography. Methods From April 28, 2017 to April 28, 2019, patients with primary aldosteronism diagnosed by ICD in Department of Endocrinology and Metabolism, Department of Cardiology and Urology were extracted from the adrenal group database of the Department of Endocrinology and Metabolism, West China Hospital of Sichuan University, and ICD diagnosis in Department of Endocrinology and Metabolism during the same period was also extracted. In patients with essential hypertension, the differences of clinical indicators and echocardiography between the two groups were compared, and the differences of cardiac damage and related risk factors between the two groups were explored. Results 295 patients were included in this study, including 148 patients in PA group (50.17%) and 147 patients in EH group (49.83%). There was no significant difference in gender, age, BMI, course of disease and average blood pressure between the two groups (P &gt; 0.05). The levels of serum aldosterone and BNP in PA group were significantly higher than those in EH group, and the levels of serum renin and minimum blood potassium were significantly lower than those in EH group (P &lt; 0.05). Left ventricular diameter (LV), left atrial diameter (LA), interventricular septal thickness (IVS), left ventricular posterior wall thickness (LVPW), ascending aorta diameter (AAO), end-diastolic diameter (EDD), end-diastolic volume (EDV) and stroke volume (SV) in PA group were significantly higher than those in EH group (P &lt; 0.05). It was significantly higher than that in EH group (P &lt; 0.05). The correlation analysis of variables with statistical significance between the two groups showed that serum renin activity level was negatively correlated with LV, AAO, EDD and SV, and the lowest serum potassium level was negatively correlated with LVPW and AAO. CONCLUSION Compared with EH of the same age, course of disease and blood pressure level, PA patients are more likely to suffer from cardiac damage, which is manifested by heart growth, ventricular septal thickening and cardiac function decline, and is closely related to the inhibition of serum renin activity and serum potassium level. Clinical attention should be paid to early screening and treatment of PA and its complications in order to reduce the risk of cardiac death.Key words: primary aldosteronism; echocardiography; cardiovascular risk factors

scholarly journals Transmethylamine‐N‐Oxide Is Associated With Diffuse Cardiac Fibrosis in People Living With HIV

2021 ◽  
Author(s):  
Nalini A. Colaco ◽  
Teresa S. Wang ◽  
Yifei Ma ◽  
Rebecca Scherzer ◽  
Olga R. Ilkayeva ◽  
...  
Keyword(s):  
Diastolic Dysfunction ◽  
Myocardial Fibrosis ◽  
Volume Fraction ◽  
Heart Function ◽  
Left Ventricular ◽  
Diffuse Myocardial Fibrosis ◽  
People Living With Hiv ◽  
Increased Risk ◽  
Biomarker Analysis ◽  
Living With Hiv

Background People living with HIV are at increased risk of developing diastolic dysfunction, heart failure, and sudden cardiac death, all of which have been characterized by higher levels of myocardial fibrosis. Transmethylamine‐N‐oxide (TMAO), a dietary gut metabolite, is linked to the development of myocardial fibrosis in animal models. However, it is unclear whether TMAO plays a role in the development of myocardial fibrosis in people living with HIV. Methods and Results The study population consisted of participants enrolled in the multisite cross‐sectional study called CHART‐HIV (Characterizing Heart Function on Anti‐Retroviral Therapy). Participants underwent echocardiography, cardiac magnetic resonance imaging, biomarker analysis, and targeted assessment of gut‐related circulating metabolites; diastolic dysfunction was determined by study‐specific criteria. Multivariable linear regression models were performed to examine the relationship of gut‐related metabolites with serum and imaging measures of myocardial fibrosis. Models were adjusted for traditional cardiovascular, inflammatory, and HIV‐related risk factors. Diastolic dysfunction was present in 94 of 195 individuals (48%) in CHART‐HIV; this cohort demonstrated higher prevalence of hypertension, hyperlipidemia, and chronic kidney disease as well as higher plasma levels of both TMAO and choline. TMAO levels were associated with parameters reflecting increased left ventricular filling pressures and with a marker of the innate immune system. TMAO levels correlated with diffuse myocardial fibrosis ( R =0.35; P <0.05) as characterized by myocardial extracellular volume fraction as well as biomarkers reflective of myocardial fibrosis. Conclusions In this study of people living with HIV, the gut metabolite TMAO was associated with underlying diffuse myocardial fibrosis and found to be a potential marker of early structural heart disease. The mechanistic role of the gut microbiome in HIV‐associated cardiovascular disease warrants further investigation. Registration URL: https://clinicaltrials.gov ; Unique identifier: NCT02860156.

scholarly journals Age-Related Cutoffs of Plasma Aldosterone/Renin Concentration for Primary Aldosteronism Screening

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Linqiang Ma ◽  
Ying Song ◽  
Mei Mei ◽  
Wenwen He ◽  
Jinbo Hu ◽  
...  
Keyword(s):  
Essential Hypertension ◽  
Retrospective Study ◽  
Primary Aldosteronism ◽  
Age Groups ◽  
Plasma Renin ◽  
Final Analysis ◽  
Plasma Aldosterone ◽  
Plasma Aldosterone Concentration ◽  
Hypertensive Patients ◽  
Age Related

Aim. This retrospective study is aimed at investigating whether aldosterone-renin ratio (ARR) cutoffs calculated by the plasma aldosterone concentration (PAC)/plasma renin concentration (PRC) should be set differently in patients of different ages. Methods. 521 hypertensive patients were screened for primary aldosteronism (PA) by the PAC/PRC. 174 patients diagnosed with PA and 311 patients with essential hypertension (EH) were included in the final analysis. Subjects were subdivided into four age groups: <40, 40–49, 50–59, and ≥60 years old. Results. The accuracy of the ARR varied greatly among the different age groups. An ARR of 3.7 (ng/dl)/(μIU/ml) had a sensitivity of 100% and a specificity of 80% in patients ≥ 60 years old. With this cutoff, the sensitivities in patients < 40, 40–49, and 50–59 years old were 74%, 82%, and 87%, respectively, and the specificities were 94%, 95%, and 94%, respectively. To achieve a sensitivity higher than 90%, the ARR cutoff needed to be lowered to 2.0 (ng/dl)/(μIU/ml) for patients 40–49 and 50–59 years old, resulting in sensitivities of 90% and 95%, respectively, and specificities of 80% and 84%, respectively. To achieve a sensitivity higher than 90%, the ARR cutoff needed to be lowered to 1.0 (ng/dl)/(μIU/ml) for patients < 40 years old, resulting in a sensitivity of 90% and a specificity of 82%. Conclusions. An ARR of 3.7 (ng/dl)/(μIU/ml) is optimal for patients ≥ 60 years; for patients 40–59 years, the optimal ARR cutoff is 2.0; for those younger than 40 years, an ARR of 1.0 may be more reasonable.

scholarly journals The relationship of epicardial obesity and levels of cardiac fibrosis markers

2019 ◽  
pp. 13-19
Author(s):  
O. V. Gritsenko ◽  
G. A. Chumakova ◽  
O. V. Gruzdeva ◽  
I. V. Shevlyakov
Keyword(s):  
Diastolic Dysfunction ◽  
Myocardial Fibrosis ◽  
Cardiac Fibrosis ◽  
Negative Relationship ◽  
Left Ventricular ◽  
Subsequent Formation ◽  
Group I ◽  
Tnf Α ◽  
Relationship Of ◽  
The Relationship

Lipotoxic myocardial damage with its fibrosis and subsequent formation of heart failure may develop due to epicardial obesity (EO). The possibility of early diagnosis of lipotoxic cardiac fibrosis is not well understood.Aim.To study the relationship of EO with the level of myocardial fibrosis markers.Material and methods.The study included 80 men aged 54,3±8,2 with grades I-III obesity. The level of metabolic factors, pro-inflammatory cytokines, adipokines (adiponectin, leptin), soluble leptin receptor and free fatty acids was determined for all patients; the presence of EO was determined by echocardiography with epicardial fat thickness (EFT) ≥7 mm. Coronary artery disease, arterial hypertension, type 2 diabetes mellitus, the presence of left ventricular diastolic dysfunction were the exclusion criteria of the study.Results.The patients were divided into 2 groups: group I with EO (n=49) and group II without EO (n=31). Group I showed a statistically significant increase in the levels of interleukin-6 (IL-6), C-reactive protein, tumor necrosis factor-α (TNF-α), leptin, a decrease in adiponectin, as well as an increase in all studied myocardial fibrosis markers. In addition, in the group with EO, a positive relationship between the EFT and TNF-α (r=0,29; p=0,041), IL-6 (r=0,28; p=0,049), leptin (r=0,41; p=0,004) and a negative relationship with the level of adiponectin (r=-0,29; p=0,042). We determine a significant effect of the degree of EO on the increase in the level of cardiac fibrosis markers (r=0,28, p=0,049), collagen (r=0,33, p=0,019), transforming growth factor-β (r=0,29, p=0,045).Conclusion.The results suggest that elevated levels of profibrotic factors in patients with EO may be signs of the presence of preclinical, and therefore, earlier lipotoxic myocardial fibrosis, which was not detected during echocardiographic research in the form of diastolic dysfunction.

scholarly journals HDAC Inhibition Reverses Preexisting Diastolic Dysfunction and Blocks Covert Extracellular Matrix Remodeling

Circulation ◽  
2021 ◽  
Author(s):  
Joshua G. Travers ◽  
Sara A. Wennersten ◽  
Brisa Peña ◽  
Rushita A. Bagchi ◽  
Harrison E. Smith ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Blood Pressure ◽  
Extracellular Matrix ◽  
Diastolic Dysfunction ◽  
Hdac Inhibitor ◽  
Cardiac Fibrosis ◽  
Regulatory Elements ◽  
Left Ventricular ◽  
Systemic Hypertension ◽  
Hdac Inhibition

Background: Diastolic dysfunction (DD) is associated with the development of heart failure (HF) and contributes to the pathogenesis of other cardiac maladies, including atrial fibrillation (AF). Inhibition of histone deacetylases (HDACs) has been shown to prevent DD by enhancing myofibril relaxation. Here, we addressed the therapeutic potential of HDAC inhibition in a model of established DD with preserved ejection fraction (EF). Methods: Four weeks following uninephrectomy (UNX) and implantation with deoxycorticosterone acetate (DOCA) pellets, when DD was clearly evident, one cohort of mice was administered the clinical-stage HDAC inhibitor ITF2357/Givinostat. Echocardiography, blood pressure measurements, and endpoint invasive hemodynamic analyses were performed. Myofibril mechanics and intact cardiomyocyte relaxation were assessed ex vivo . Cardiac fibrosis was evaluated by picrosirius red (PSR) staining and second harmonic generation (SHG) microscopy of left ventricular (LV) sections, RNA-sequencing of LV mRNA, mass spectrometry-based evaluation of decellularized LV biopsies, and atomic force microscopy (AFM) determination of LV stiffness. Mechanistic studies were performed with primary rat and human cardiac fibroblasts. Results: HDAC inhibition normalized DD without lowering blood pressure in this model of systemic hypertension. Surprisingly, in contrast to prior models, myofibril relaxation was unimpaired in UNX/DOCA mice. Furthermore, cardiac fibrosis was not evident in any mouse cohorts based on PSR staining or SHG microscopy. However, mass spectrometry revealed induction in the expression of more than one hundred extracellular matrix (ECM) proteins in LVs of UNX/DOCA mice, which correlated with profound tissue stiffening based on AFM. Remarkably, ITF2357/Givinostat treatment blocked ECM expansion and LV stiffening. The HDAC inhibitor was subsequently shown to suppress cardiac fibroblast activation, at least in part, by blunting recruitment of the pro-fibrotic chromatin reader protein, BRD4, to key gene regulatory elements. Conclusions: These findings demonstrate the potential of HDAC inhibition as a therapeutic intervention to reverse existing DD, and establish blockade of ECM remodeling as a second mechanism by which HDAC inhibitors improve ventricular filling. Additionally, our data reveal the existence of pathophysiologically relevant 'covert' or 'hidden' cardiac fibrosis that is below the limit of detection of histochemical stains such as PSR, highlighting the need to evaluate fibrosis of the heart using diverse methodologies.

scholarly journals Association and diagnostic utility of diastolic dysfunction and myocardial fibrosis in patients with Fabry disease

Open Heart ◽  
2018 ◽  
Vol 5 (2) ◽  
pp. e000803 ◽  
Author(s):  
Dan Liu ◽  
Daniel Oder ◽  
Tim Salinger ◽  
Kai Hu ◽  
Jonas Müntze ◽  
...  
Keyword(s):  
Strain Rate ◽  
Diastolic Dysfunction ◽  
Fabry Disease ◽  
Myocardial Fibrosis ◽  
Cardiac Fibrosis ◽  
Left Atrial Volume ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Functional Impairments ◽  
Ventricular Ejection Fraction

ObjectivesCurrent guidelines highlight important therapy implications of cardiac fibrosis in patients with Fabry disease (FD). However, association between morphological and functional impairments with cardiac fibrosis in hereditary cardiomyopathies remains elusive. We investigated the association between echocardiography-determined cardiac dysfunction and cardiac MRI (cMRI)-detected myocardial fibrosis (late gadolinium enhancement, LE) in patients with FD with preserved left ventricular ejection fraction (≥50%).Methods146 patients with FD (aged 39±14 years, 57 men) were analysed, all receiving echocardiography and cMRI within a 1 week interval. Longitudinal systolic strain (LS_sys), strain rate (LSr_sys) and diastolic strain rate (LSr_E/LSr_A) were assessed using speckle-tracking imaging. Receiver operating characteristic (ROC) analysis was performed to identify the diagnostic performance of various markers for LE.ResultsLE was detected in 57 (39%) patients with FD. LV wall thickness, left atrial volume, septal E/e′, diastolic dysfunction grade, global LS_sys and E/LSr_E, mid-lateral LS_sys and LSr_E, as well as N-terminal pro-brain natriuretic peptide were all associated with LE independent of age, sex, body mass index, New York Heart Association functional class and kidney function. In ROC curve analysis, septal E/e′ performed best (area under the curve=0.86, 95% CI=0.79 to 0.92). Septal E/e′>14.8 was strongly associated with LE (specificity=97.8% and sensitivity=49.1%). In 9% of patients, localised LE was present even though no other cardiac or kidney abnormalities were detected.ConclusionsEchocardiography-derived diastolic dysfunction is closely linked to LE in FD. Septal E/e′ ratio is the best echocardiographic marker suggestive of LE. Diastolic dysfunction is not a prerequisite for LE in FD, since LE can be detected in the absence of measurable cardiac functional impairments.Trial registration numberClinicalTrials.gov Identifier (NCT03362164).

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