Left Ventricular Hypertrophy Research Articles

Effect of Balloon-Dilated Restenosis on Exercise Performance and Cardiac Function in Children After Coarctation Repair.

Restenosis occurs commonly after aortic coarctation (CoA) repair, usually requiring treatment by balloon dilation. Its effect on physical exercise performance is not documented. A retrospective analysis of exercise testing and echocardiographic assessment was performed in children after CoA repair. A group without restenosis (= group 1) and a group with recoarctation, treated by single balloon dilation (= group 2) were compared by matching for age and gender at a 2:1 ratio. Group 1 included 40 children and group 2 comprised 21 children, with mean age of 12.3 ± 2.3y and 11.9 ± 2.9y (p = 0.536) at evaluation. Group 2 children were younger at CoA repair (group 1: median 32.0d (11.0-188.0)-group 2: 9.0d (5.5-19.0), p = 0.011). Arterial hypertension was frequently noticed (group 1: 23(57.5%)-group 2: 7(33.3%), p = 0.106). Echocardiography revealed comparable cardiac function properties, showing more left ventricular (LV) hypertrophy in all CoA patients compared to their peers (Posterior wall thickness z-value: 1.03 ± 1.65, p < 0.001)). Exercise results were generally comparable, despite small differences in favor of group 1 (predicted % peak VO2 = group 1: 95.2 ± 21.4%-group 2: 82.3 ± 10.5%, p = 0.024; peak VO2/kg = group 1: 38.9 ± 9.5ml/min/kg-group 2: 33.8 ± 6.9ml/min/kg, p = 0.034; VO2/WR slope = group 1: 12.6 ± 2.0ml/min/watt-group 2: 11.3 ± 1.7ml/min/watt, p = 0.018). Compared to uncomplicated coarctation patients, children developing a surgical restenosis after CoA repair, and treated effectively by balloon dilation, had lower-but still acceptable-oxygen uptake during exercise. As intrinsic cardiovascular function characteristics were similar, further study to evaluate the impact of non-disease-specific factors is mandatory.

Cross-Sectional Association Between Left Ventricular Geometric Patterns, Cortical Cerebral Microinfarcts, and Cognition.

Left ventricular (LV) geometric patterns are associated with cognitive impairment and cerebral small vessel disease. As a novel magnetic resonance imaging marker of cerebral small vessel disease and a risk factor for cognitive dysfunction, cortical cerebral microinfarcts (CMIs) have been associated with heart disease through mechanisms including cardioembolism and cerebral hypoperfusion. Further investigation is required to determine whether cortical CMIs could arise from hemodynamic changes related to LV geometry, thus elucidating the connection between LV geometry and cognitive function. This study aims to investigate the cross-sectional relationship between LV geometric patterns, cortical CMIs, and cognition. A total of 261 patients, aged 75.3±6.8 years, were enrolled from a memory clinic study. LV dimensions were obtained using 2-dimensional echocardiography. LV mass index and relative wall thickness were determined to categorize LV geometric patterns. Cortical CMIs were graded on 3T magnetic resonance imaging. Cognition was assessed using neuropsychological tests and clinical diagnosis. Linear, zero-inflated Poisson, and logistic regression were employed for continuous, count, and binary outcomes, respectively. Mediation analysis was conducted to examine the mediation effect of cortical CMIs. A significant association was observed between concentric LV hypertrophy and cortical CMI counts (rate ratio, 3.85 [95% CI, 1.85-8.01]), as well as the odds of having dementia (odds ratio, 2.86 [95% CI, 1.07-7.89]), in the fully adjusted model. Cortical CMIs may partly explain the relationship between concentric LV hypertrophy and cognitive function. Concentric LV hypertrophy was associated with cortical CMIs and dementia. Further verification is warranted to determine the role of cortical CMIs in the association between LV geometry and cognition.

Investigation of a targeted panel of gut microbiome-derived toxins in children with chronic kidney disease.

The gut-kidney axis is implicated in chronic kidney disease (CKD) morbidity. We describe how a panel of gut microbiome-derived toxins relates to kidney function and neurocognitive outcomes in children with CKD, consisting of indoleacetate, 3-indoxylsulfate, p-cresol glucuronide, p-cresol sulfate, and phenylacetylglutamine. The Chronic Kidney Disease in Children (CKiD) cohort is a North American multicenter prospective cohort that enrolled children aged 6months to 16years with estimated glomerular filtration rate (eGFR) 30-89ml/min/1.73 m2. Data from the 2-year study visit were used for this analysis. Toxin quantification (Metabolon Inc., Durham, NC) was performed with ultra-high performance liquid chromatography/tandem mass spectrometry. Executive function and echocardiograms were assessed. Regression analysis examined the association of toxin levels with eGFR, CKD etiology, and neurocognitive and cardiac assessments (adjusted for age, sex, and urine protein:creatinine [UPCR]). There were 150 CKiD participants included in this study. All toxins levels were significantly inversely correlated with eGFR (Spearman's rho - 0.45 to - 0.69). Children with non-glomerular CKD had significantly higher levels of 3-indoxylsulfate, phenylacetylglutamine, and p-cresol glucuronide. The toxin levels did not associate with neurocognitive outcomes. P-cresol glucuronide and phenylacetylglutamine negatively associated with left ventricular mass index z score, but did not associate with left ventricular hypertrophy. Children with CKD have high levels of circulating gut microbiome-derived toxins. The levels of these toxins are strongly correlated with eGFR. There appear to be differences in toxin level based on glomerular versus non-glomerular etiology, even when accounting for the differences in eGFR between these two subgroups. In this sample, we did not detect any associations between these toxin levels and neurocognitive or cardiac outcomes.

Efficacy and safety of cardiac myosin inhibitors for symptomatic hypertrophic cardiomyopathy: a meta-analysis of randomized controlled trials

IntroductionHypertrophic cardiomyopathy (HCM) is a common genetic heart disorder. It is characterized by left ventricular hypertrophy and impaired cardiac function, with forms categorized into obstructive (oHCM) and nonobstructive (nHCM). Traditional treatments address symptoms but not the underlying disease mechanism, highlighting the need for novel therapies. Cardiac myosin inhibitors such as mavacamten and aficamten present potential new treatment options.MethodsA meta-analysis of randomized controlled trials (RCTs) was conducted following PRISMA guidelines. Studies comparing cardiac myosin inhibitors with placebo were reviewed, and outcomes related to NYHA functional class, Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS), LVOT gradients, and left ventricular ejection fraction (LVEF) were analyzed.ResultsSix RCTs involving 826 participants demonstrated that mavacamten and aficamten significantly improved NYHA functional class and KCCQ-CSS scores. The incidence of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) was similar between the treatment and control groups, indicating a comparable safety profile.ConclusionCardiac myosin inhibitors are effective in improving cardiac function and reducing LVOT obstruction in HCM patients. They offer a promising alternative to current treatments, with a safety profile comparable to placebo. Further research is needed to confirm long-term benefits.

Cardiac Magnetic Resonance Imaging in Diagnostics and Cardiovascular Risk Assessment

Cardiac magnetic resonance (CMR) allows for analysis of cardiac function and myocardial tissue characterization. Increased left ventricular mass (LVM) is an independent predictor of cardiovascular events; however, the diagnosis of left ventricular hypertrophy and its prognostic value strongly depend on the LVM indexation method. Evaluation of the quantity and distribution of late gadolinium enhancement assists in clinical decisions on diagnosis, cardiovascular assessment, and interventions, including the placement of cardiac implantable electronic devices and the choice of an optimal procedural approach. Novel CMR techniques, such as T1 and T2 mapping, may be used for the longitudinal follow-up of myocardial fibrosis and myocardial edema or inflammation in different groups of patients, including patients with systemic sclerosis, myocarditis, cardiac sarcoidosis, amyloidosis, and both ischemic and non-ischemic cardiomyopathy, among others. Moreover, CMR tagging and feature tracking techniques might improve cardiovascular risk stratification in patients with different etiologies of left ventricular dysfunction. This review summarizes the knowledge about the current role of CMR in diagnostics and cardiovascular risk assessment to enable more personalized approach in clinical decision making.

Impact of Preventive Intravenous Amiodarone on Reperfusion Ventricular Fibrillation in Patients With Left Ventricular Hypertrophy Undergoing Open-Heart Surgery: Randomized Controlled Clinical Trial.

Ventricular fibrillation (VF) is a vicious arrhythmia usually generated after removal of the aortic cross-clamp (ACC) in patients undergoing open-heart surgery, which could damage cardiomyocytes, especially in patients with left ventricular hypertrophy (LVH). Amiodarone has the prominent properties of converting VF and restoring sinus rhythm. However, few studies concentrated on the effect of amiodarone before ACC release on reducing VF in patients with LVH. The study was designed to explore the effectiveness of prophylactic intravenous amiodarone in reducing VF after the release of the ACC in patients with LVH. A total of 54 patients with LVH scheduled for open-heart surgery were enrolled and randomly divided (1:1) into 2 groups-group A (amiodarone group) and group P (placebo-controlled group). Thirty minutes before removal of the ACC, the trial drugs were administered intravenously. In group A, 150 mg of amiodarone was pumped in 15 minutes. In group P, the same volume of normal saline was pumped in 15 minutes. The primary outcome was the incidence of VF 10 minutes after removal of the ACC. The incidence of VF was lower in group A than in group P (30% vs 70%, P=.003). The duration of VF, the number of defibrillations, and the defibrillation energy were also lower in group A than in group P (P<.001, P=.002, and P=.002, respectively). After the end of cardiopulmonary bypass, the heart rate and mean arterial pressure were lower in group A, and the mean pulmonary arterial pressure and the dose of vasoactive drugs were higher than those in group P (P<.001, P<.001, P=.04, and P=.02, respectively). However, there were no significant differences in the use of vasoactive-inotropic agents and hemodynamic status between the 2 groups before the end of surgery. In patients with LVH who undergo open-heart surgery, amiodarone can be safely used to reduce the incidence of VF, the duration of VF, the frequency of defibrillation, and the energy of defibrillation after ACC removal.

NASCI case of the month: "pseudo normalization of T1 values in Anderson-Fabry disease".

Anderson-Fabry disease (AFD) is a X-linked lysosomal storage disorder that can result in cardiac dysfunction including left ventricular hypertrophy (LVH) and conduction abnormalities (Frontiers in cardiovascular medicine vol. 10) [1]. The manifestations of AFD in women may be isolated to one organ and occur late in life due to the random inactivation of the X chromosome. This non-classic presentation may make reaching a diagnosis more difficult. In our case, a 63-year-old woman with family history of AFD presenting with chest pain underwent echocardiography which showed LVH. Cardiac magnetic resonance (CMR) was performed confirming LVH as well as identifying extensive late gadolinium enhancement. T1 values were normal. Despite normal T1 values and female sex, a diagnosis of cardiac involvement of AFD should still be considered and was confirmed with genetic testing.

The Effect of Genotype Differences on Cardiac Involvement in Cases Diagnosed with Duchenne Muscular Dystrophy.

Duchenne muscular dystrophy (DMD) is the most frequently seen muscular disease in childhood. Cardiac involvement is extremely important in terms of morbidity and mortality in these patients. Different studies have shown that mutations occurring in various exons are cardioprotective or increase cardiac involvement in DMD cases. The aim of this study was to examine the effect of genotype differences on cardiac involvement in patients diagnosed with DMD with genetic analysis. A retrospective analysis of DMD patients followed up in the Muscle Diseases Centre of Health Sciences University Izmir Tepecik Training and Research Hospital was done. Evaluation was made of 120 male DMD patients with a mean age of 9.66 ± 5.10 years. According to the genetic analysis results, 76.7% deletions, 15.8% mutations, and 7.5% duplications were determined. Of the mutations determined, 65.8% were between exons 44 and 54, 17.5% between exons 1 and 18, and 9.2% between exons 19 and 43, 5.8% were non-sense mutations, and 1.7% were on exons >54. In the cases determined with cardiac involvement, the mean age of onset was 11.87 ± 3.11 years. When ejection fraction (EF) <56% or fractional shortening (FS) <28% was accepted as systolic dysfunction cardiac effect, 12.5% of the cases were determined with cardiac involvement. Of the cases determined with cardiac effects, 86.7% were aged >10 years. Electrocardiography was evaluated as normal in 54.5%, sinus tachycardia in 24.2%, short PR in 15.2%, and right and left ventricle hypertrophy in 8.1%. No statistically significant difference was determined in mutation types and location according to the age of cardiac involvement. The left ventricle (LV) posterior wall thickness value determined in the exon 44-54 group was higher than in DMD cases with other mutations. Although not statistically significant, an important result was that the LV posterior wall and IVSed values were evaluated to be high. The current study results and findings in literature have not found a clear relationship between genotypes and cardiac involvement in DMD cases.

The impact of combination of zofenopril and different diuretics on regression of myocardial reperfusion injury and oxidative status in spontaneously hypertensive rats.

As several decades of research have shown the cardioprotective effects of angiotensin-converting enzyme (ACE) inhibitors alone or in combination with diuretics, we were interested in investigating the effects of subchronic therapy of these drugs on ischemia-reperfusion (I/R) damage to the heart, as well as their influence on oxidative status. The research was conducted on 40 spontaneously hypertensive male Wistar Kyoto rats, divided into 4 groups. Animals were treated for four weeks with 10mg/kg/day zofenopril alone or in combination with hydrochlorothiazide, indapamide and spironolactone per os. After the treatment, hemodynamic measurements, echocardiography and assessment of myocardial function were performed according to Langendorff's retrograde perfusion method. The induced global ischemia model involved 20min of ischemia followed by 30min of reperfusion to the heart (I20:R30). Markers of oxidative stress were determined spectrophotometrically from plasma and erythrocyte lysates. Heart and kidney tissue samples were pathohistologically analyzed. Treatment with a combination of ACE inhibitors and diuretics significantly lowered blood pressure in spontaneously hypertensive rats, alleviated left ventricular hypertrophy and increased ejection fraction. On the other hand, treatment with zofenopril and diuretics showed pro-oxidative potential. Pathohistological analysis of heart and kidney tissue samples indicates that subchronic administration of antihypertensive agents does not lead to significant changes in these organs. Since the antihypertensive therapy was relatively short (only 4weeks), in order to elucidate or deny the prooxidative mechanism, additional studies of a longer time interval are needed and planned.

Left ventricular hypertrophy in young hypertensives: the possible crosstalk of mTOR and angiotensin-II -a case-control study

BackgroundHypertension is a major cause of cardiac dysfunction. The earliest manifestation is left ventricular remodeling/hypertrophy. The occurrence of adverse cardiac remodeling and outcomes occurs irrespective of age in blacks. This necessitated an estimate of the prevalence of left ventricular hypertrophy (LVH) and an assessment of the roles of the mammalian target organ of rapamycin (mTOR) and angiotensin-II (Ang II) as possible pathogenic markers of LVH among young hypertensives.MethodsThis prospective case-control study involved 110 hypertensive and 60 normotensive (control) participants aged 18–45 across tertiary hospitals in Ekiti state. Ethical approval was obtained from all the various institutions. Participants were recruited consecutively after giving informed consent. Sociodemographic/clinical information, resting electrocardiogram and echocardiography were obtained. Venous blood was obtained to estimate mTOR, Ang II, Chemerin, lipids – triglyceride (TG), high-density lipoprotein (HDL), total cholesterol (TC), troponin-T, NF-Kβ, and Galectin-3 using enzyme-linked immunosorbent assay.ResultsThe prevalence of LVH among the hypertensive group was 20.9%, 39%, 11.01%, and 15.74% using 2D-transthoracic echocardiography, Sokolow-Lyon, Cornell’s and Cornell product ECG criteria. Also, hypertensives with LVH had a significantly increased blood pressure, body mass index, serum level of TG, TG/HDL, TC/HDL, chemerin, troponin T, Galectin-3 and total mTOR compared to normotensive and hypertensives without LVH. At the same time, serum NF-kβ and Ang II were only significant when compared with normotensive but not hypertensives without LVH. The total mTOR moderately correlated positively with ANG-II.ConclusionsThe results suggest an interaction between mTOR and Ang II in the development of LVH. In addition, it shows that LVH is associated with dyslipidemia, inflammation, and fibrosis.

Effect of obesity on cardiovascular remodeling, and aerobic capacity in adults with coarctation of aorta.

We hypothesized that patients with coarctation of aorta (COA) and obesity would have more advanced cardiovascular remodeling and impaired aerobic capacity compared to COA patients without obesity. The purpose of this study was to assess the relationship between obesity, cardiovascular remodeling, and aerobic capacity in adults with repaired COA. The study comprised of 3 groups: (1) Obese COA group (n=177) (COA patients with body mass index [BMI] >30 kg/m2); (2) Non-obese COA group (n=572) (COA patients with BMI ≤30 kg/m2); (3) Control group (n=59) (subjects without structural heart disease and BMI ≤30 kg/m2). Cardiovascular remodeling was assessed using the following indices: (1) Arterial stiffness - total arterial compliance index (TACI). (2) Left ventricular hypertrophy - LV mass (LVM) and relative wall thickness (RWT). (3) LV diastolic function - Doppler-derived estimated LV end-diastolic pressure (LVEDP) and Tau. (4) Right ventricular (RV)-pulmonary artery coupling - RV free wall strain and RV systolic pressure (RVFW/RVSP). Aerobic capacity was assessed using predicted peak oxygen consumption (VO2). The obese COA group had higher LVM, RWT, LVEDP, and Tau, as well as lower RVFWS/RVSP, TACI and peak VO2 compared to non-obese COA group and controls. There was a correlation between BMI and LVM (r=0.39, p<0.001), RWT (r=0.47, p<0.001), LVEDP (r=0.43, p<0.001), tau (r=0.22, p=0.008), RVFWS/RVSP (r=- 0.24, p<0.001), and predicted peak VO2 (r=-0.48, p<0.001). These findings underscore the cardiovascular implications of obesity in the setting of COA, and provide opportunities for interventions to address obesity, and improve outcomes in this population.

Quantitative assessment of left ventricular function by left ventricular pressure-strain loop in patients with end-stage renal disease.

A new and non-invasive technology of left ventricular pressure-strain loop (LV-PSL) has recently been used to provide information on myocardial work (MW) and identify subtle modifications in cardiac function. This study aimed to use LV-PSL for early identification of changes in LV structure and MW in patients with end-stage renal disease (ESRD). Methods： Seventy-two patients with ESRD were divided into two groups based on undergoing maintenance hemodialysis (MHD), namely the dialysis group (ESRD-D group) and non-dialysis group (ESRD-ND group). Thirty age- and sex-matched control participants were enrolled in the N group. Traditional echocardiography and LV-PSL measurements were conducted. The values of Global longitudinal strain (GLS), peak strain dispersion (PSD), global constructive work (GCW), global wasted work (GWW), global work index (GWI), and global work efficiency (GWE) were assessed. Results：The most prevalent anomaly in ESRD patients was left ventricular (LV) hypertrophy. The GLS value was significantly lower and PSD was higher in patients with ESRD than in controls. Furthermore, patients with ESRD had severely higher GWW values and lower GWE than the N group (p< 0.05). No significant differences were found in GWI and GCW between the three groups (p> 0.05). Correlation analysis showed that GCW, GWI and GWE were positively correlated with LV ejection fraction (EF) and negatively correlated with GLS. GWW was negatively correlated with LVEF and positively correlated with GLS and PSD. In addition, GWE was negatively correlated with PSD (all p< 0.05). Conclusions：Patients with ESRD have LV structural and functional abnormalities. LV-PSL measurement can be helpful in identifying these subclinical abnormalities. MHD did not change myocardial workload in patients with ESRD.

The Role of NT-proBNP Levels in the Diagnosis of Hypertensive Heart Disease.

Hypertension is a major risk factor of various cardiac complications, including hypertensive heart disease (HHD). This condition can lead to a number of structural and functional changes in the heart, such as left ventricular hypertrophy, diastolic dysfunction, and, eventually, systolic dysfunction. In the management of hypertensive heart disease, early diagnosis and appropriate treatment are crucial for preventing the progression to congestive heart failure. One potential diagnostic marker that has gained attention in recent years is the N-terminal pro-brain natriuretic peptide (NT-proBNP). The natriuretic peptides, including the brain natriuretic peptide (BNP) and its inactive N-terminal fragment, are secreted by the myocardium in response to increased wall stress and volume overload. In patients with hypertensive heart disease, increased NT-proBNP levels may reflect the structural and functional changes occurring in the myocardium as a result of chronic pressure overload. Several studies have investigated the diagnostic utility of NT-proBNP in hypertensive heart disease. NT-proBNP levels can be a useful adjunct in the diagnosis of hypertensive heart disease, particularly in the assessment of diastolic dysfunction and left ventricular hypertrophy. This review paper explores the role of NT-proBNP levels in the diagnosis of hypertensive heart disease.

A case of renovascular hypertension due to polyarteritis nodosa.

In renal vasculitis, luminal narrowing can reduce blood flow and activate the renin-angiotensin-aldosterone system, causing renovascular hypertension. We present the case of a 47-year-old man with previous intestinal tuberculosis and episodes of lumbar pain, tender erythematous nodules and arthralgias. He had grade 3 hypertension, unresponsive to treatment, with left ventricular concentric hypertrophy and chronic kidney disease. He was admitted to the ICU due to a hypertensive emergency, with acute kidney failure and a large peri-renal hematoma. The computed tomography and angiography showed bilateral renal scarring, intrarenal pseudoaneurysms and irregularities in the renal, common hepatic and mesenteric arteries, suggesting a medium-vessel vasculitis, namely polyarteritis nodosa. Cyclophosphamide and corticosteroids were started. His blood pressure was controlled, and his kidney function remained stable. Renovascular hypertension is, in infrequent cases, caused by an inflammatory systemic disease. When this is the case, the diagnosis must be considered and appropriately addressed.

Investigating the role of age, admission systolic blood pressure, and neutrophil-to-lymphocyte ratio in predicting left ventricular hypertrophy among patients with primary hypertension

Objective In patients with primary hypertension (PH), left ventricular hypertrophy (LVH) is a critical predictor of cardiovascular events. We aimed to identify clinical and laboratory predictors of LVH in patients with PH. Methods This retrospective cohort study included 2321 patients with PH at the Fifth Affiliated Hospital of Xinjiang Medical University from December 2022 to January 2024. Patients were classified into LVH and non-LVH groups; LVH was defined as left ventricular mass index (LVMI) &gt;115 g/m2 for men and &gt;95 g/m2 for women. Univariate and multivariate logistic analysis were used to identify risk factors for LVH. Results Univariate analysis revealed significant differences between the LVH and non-LVH groups in age, sex, smoking, systolic blood pressure (SBP), neutrophil-to-lymphocyte ratio (NLR), body mass index, serum creatinine (SCr), lymphocyte count, and hypertension duration. Multivariate analysis identified age, sex, SBP, SCr, and NLR as independent risk factors for LVH. A combined receiver operating characteristic (ROC) model had an area under the ROC curve of 0.711 (95% CI: 0.68–0.74), with 75.3% sensitivity and 59.2% specificity. Conclusion Age, sex, SBP, SCr, and NLR were independent predictors for LVH in patients with PH. Our combined diagnostic model provides valuable insight for early LVH screening, aiding timely clinical intervention.

An ECG-Based Model for Left Ventricular Hypertrophy Detection: A Machine Learning Approach.

Goal: Despite the high incidence of left ventricular hypertrophy (LVH), clinical LVH-electrocardiography (ECG) criteria remain unsatisfactory due to low sensitivity. We propose an automatic LVH detection method based on ECG-extracted features and machine learning. Methods: ECG features were automatically extracted from two publicly available databases: PTB-XL with 2181 LVH and 9001 controls, and Georgia with 1012 LVH and 1387 controls. After preprocessing and feature extraction, the most relevant features from PTB-XL were selected to train three models: logistic regression, random forest (RF), and support vector machine (SVM). These classifiers, trained with selected features and a reduced set of five features, were evaluated on the Georgia database and compared with clinical LVH-ECG criteria. Results: RF and SVM models showed accuracies above 90% and increased sensitivity to above 86%, compared to clinical criteria achieving 38% at maximum. Conclusions: Automatic ECG-based LVH detection using machine learning outperforms conventional diagnostic criteria, benefiting clinical practice.

Automated electronic health record-based screening for Fabry disease in unexplained left ventricular hypertrophy (FAPREV-HCM)

Background and aimsHypertrophic cardiomyopathy (HCM) has various aetiologies, including genetic conditions like Fabry disease (FD), a lysosomal storage disorder. FD prevalence in high-risk HCM populations ranges from 0.3% to 11.8%....

Mineralocorticoid axis activity and cardiac remodeling in patients with ACTH dependent Cushing's syndrome.

Arterial hypertension and left ventricular hypertrophy and remodeling are independent cardiovascular risk factors in patients with Cushing's syndrome. Changes in the renin-angiotensin system and in the mineralocorticoid axis activity could be involved as potential mechanisms in their pathogenesis, in addition to cortisol excess. In this ancillary study of our previous study prospectively investigating patients with ACTH-dependent Cushing's syndrome by cardiac magnetic resonance imaging (NCT02202902), 11 patients without any interfering medication were cross-sectionally compared to 20 control subjects matched for age, sex and body mass index. Angiotensin metabolites and adrenal steroids were measured by liquid chromatography tandem mass spectrometry and their relation to blood pressure and cardiac structure was evaluated. Concentrations of angiotensin I and angiotensin II were comparable, but the angiotensin-converting enzyme activity was significantly lower (2.19 (1.67;3.08) vs 4.07 (3.1;5.6); p<0.001) in patients compared to controls. Aldosterone concentrations were significantly lower (6.9 (6.9;124.1) vs 239.9 (181.4;321.9) pmol/l; p<0.001) in the group of patients, but adrenal aldosterone precursor metabolites were comparable between patients and controls. Inverse correlations were observed for 24h urinary free cortisol and aldosterone with the ratio of left ventricular mass to end-diastolic volume (r=0.470, p=0.012 and r= -0.367, p=0.046, respectively). We describe a disease specific profile of angiotensin metabolites in patients with ACTH dependent Cushing's syndrome. Low levels of aldosterone in the presence of unchanged precursor metabolites indicate a direct inhibitory action of cortisol excess on the aldosterone synthase. Further, glucocorticoid excess per se drives cardiac muscle remodeling.

Comparison of Influence of Office and 24-h Central Aortic Blood Pressure on Target Organ Damage in Hypertension.

The aim of this study was to explore whether 24-h ambulatory central (aortic) blood pressure (BP) has an advantage over office central aortic BP in screening for hypertension-mediated target organ damage (HMOD). A total of 714 inpatients with primary hypertension and the presence of several cardiovascular risk factors or complications involving clinical HMOD were enrolled. Twenty-four hour central aortic BP was measured by means of a noninvasive automated oscillometric device (Mobil-O-Graph). Office BP was measured with a validated oscillometric Omron device after a 5-min rest in a sitting position. Central aortic pressure waveforms were derived from the radial pressure waveforms with a validated transfer function of the Sphygmocor software, version 8.0 (Atcor Medical, Sydney, Australia). Carotid-femoral pulse wave velocity (cf-PWV) measurement was performed by sequential placement of the transducer on the femoral artery and carotid artery and determining transit time between the two pulses in reference to the R wave of the ECG. cf-PWV was calculated as the measured distance from the suprasternal notch to the femoral artery minus the distance from the suprasternal notch to the carotid artery divided by the pulse transit time. HMOD was defined as the presence of carotid intima-media thickness (IMT) above normal values and/or carotid plaque, left ventricular hypertrophy (LVH), renal abnormalities as assessed by urine albumin/creatinine ratio (ACR) above normal values and/or estimated glomerular filtration rate (eGFR) less than 60mL/min/1.73m2 and/or increased cf-PWV>10m/s. In the study cohort of 714 (age 54.52±13.24years, 74.6% male) patients with primary hypertension, LV mass index (LVMI) was significantly higher in males (p<0.002) and eGFR was significantly lower in males (p<0.001). However, there was no statistical significance between males and females in IMT, ACR, and cfPWV. When accounting for confounding factors (age, sex, BMI, triglycerides, total cholesterol, LDL, glucose, smoking, and heart rate), central systolic (cSBP), diastolic (DBP), and pulse (cPP) pressure obtained with 24-h monitoring was more strongly correlated with LVMI than office measurements. Twenty-four hour cSBP and cPP were more strongly correlated with IMT than those of office monitoring. The 24-h augmentation index (AIx) was more strongly correlated with eGFR than office AIX. Twnety-four hour cSBP and cPP were more strongly correlated with lgACR. Office AIx and cPP were more strongly correlated with c-fPWV than 24-h measurements while cSBP, DBP, and cPP obtained by both methods were equally correlated with c-fPWV. Ambulatory central (aortic) pressure may be more strongly related to HMOD than office CAP which may have an advantage in screening for c-fPWV. Trial Registration: Registration number: ChiCTR2000040308.

Outcomes after medical treatment for primary aldosteronism: an international consensus and analysis of treatment response in an international cohort.

Primary aldosteronism can be treated medically but there is no standardised method to evaluate treatment outcomes. We aimed to develop criteria for assessing the outcomes of targeted medical treatment of primary aldosteronism, analyse outcomes across an international cohort, and identify factors associated with a complete treatment response. An international panel of 31 primary aldosteronism experts used the Delphi method to reach consensus on the definition of complete, partial, or absent biochemical and clinical outcomes of medical treatment of primary aldosteronism. Clinical data at baseline and 6-12 months post-treatment were collected from patients with primary aldosteronism who started targeted medical treatment between 2016 and 2021 at 28 participating centres. Consensus was reached for defining complete, partial, or absent biochemical or clinical response. Of 1258 patients (with a mean age of 52 years [SD 11·5] and of whom 610 [48·5%] were female and 648 [51·5%] were male), 1057 (84·0%) had biochemical outcome data (559 [52·9%] had a complete biochemical response). The median daily dose of spironolactone was significantly higher for those with a complete biochemical response than for those without (40 mg [IQR 25-50] vs 25 mg [20-50]; p=0·011). Of the 1248 patients with clinical outcome data, 228 [18·3%] had a complete clinical response whereas 227 (18·2%) had an absent response. Patients with a complete clinical response were more likely than those with partial or absent clinical response to be women (OR 2·099, 95% CI 1·485-2·968; p<0·001), require lower doses of antihypertensive drugs at baseline (0·687, 0·603-0·782; p<0·001), and were less likely to have microalbuminuria or left ventricular hypertrophy (0·584, 0·391-0·873; p=0·009). The Primary Aldosteronism Medical Treatment Outcome (PAMO) criteria represent an internationally developed outcome standard that can guide clinical practice and research into primary aldosteronism. Efforts to optimise treatment intensity and minimise factors associated with an absent treatment response are needed to improve patient outcomes. None. For the Chinese (simple), Chinese (complex), Japanese, Korean, German, French, Spanish, Dutch, Swedish, Slovenian, Polish, Italian and Russian translations of the abstract see Supplementary Materials section.