Progression Of Left Ventricular Hypertrophy Research Articles

Fabry disease: development and progression of left ventricular hypertrophy despite long-term enzyme replacement therapy

BackgroundEnzyme replacement therapy (ERT) may halt or attenuate disease progression in patients with Anderson-Fabry disease (AFD). However, whether left ventricular hypertrophy (LVH) can be prevented by early therapy or may...

Prospective Study of Modifiable Risk Factors of Arterial Hypertension and Left Ventricular Hypertrophy in Pediatric Patients on Hemodialysis

IntroductionFluid and salt overload in dialysis patients result in high blood pressure (BP), left ventricular hypertrophy (LVH) and hemodynamic instability, resulting in cardiovascular morbidity and mortality. MethodsAnalysis of 910 pediatric patients on maintenance hemodialysis/hemodiafiltration (HD/HDF), prospectively followed with 2758 observations recorded every 6-months in the International Pediatric Hemodialysis Network. ResultsUncontrolled hypertension was present in 55% of observations, with 27% of patients exhibiting persistently elevated pre-dialysis BP. Systolic and diastolic, height- and age-standardized BP (BP-SDS) were independently associated with number of antihypertensive medications (OR=1.47 [1.39-1.56], 1.36 [1.23-1.36]) and interdialytic weight gain (IDWG; 1.19 [1.14-1.22], 1.09 [1.06-1.11]). IDWG was related to urine output (OR=0.27 [0.23-0.32]) and dialysate sodium (dNa; 1.06 [1.01-1.10]; all p<0.0001). In subjects with pre-dialysis and 24h-BP measurements, the prevalence of masked hypertension was 24%, and HD versus HDF use was an independent risk factor of elevated MAP-SDS (OR=2.28 [1.18-4.41], p=0.01).51% of 1135 echocardiograms demonstrated LVH. Modifiable risk factors included pre-dialysis systolic BP-SDS (OR=1.06 [1.04-1.09], p<0.0001), blood hemoglobin (0.97 [0.95-0.99], HD versus HDF modality (1.09 [1.02-1.18], p=0.01) and IDWG (1.02 [1.02-1.03], p=0.04). Additionally HD modality increased the risk of LVH progression (OR=1.23 [1.03-1.48]). Intradialytic hypotension (IDH) was prevalent in patients progressing to LVH and independently associated with pre-dialysis BP-SDS below 25th percentile, lower number of antihypertensives, HD versus HDF modality, ultrafiltration rate and urine output, but not with dNa. ConclusionsUncontrolled hypertension and LVH are common in pediatric hemodialysis, despite intense pharmacological therapy. Outcome may improve with use of HDF, and superior anemia and IDWG control; the latter via lowering dNa, without increasing the risk of IDH.

Exploring the implications of blocking renin-angiotensin-aldosterone system and fibroblast growth factor 23 in early left ventricular hypertrophy without chronic kidney disease.

Whether fibroblast growth factor 23 (FGF23) directly induces left ventricular hypertrophy (LVH) remains controversial. Recent studies showed an association between FGF23 and the renin-angiotensin-aldosterone system (RAAS). The aim of this study was to investigate changes in FGF23 levels and RAAS parameters and their influences on LVH. In the first experiment, male C57BL/6J mice were divided into sham and transverse aortic constriction (TAC) groups. The TAC group underwent TAC at 8 weeks of age. At 1, 2, 3, and 4 weeks after TAC, the mice were sacrificed, and blood and urine samples were obtained. Cardiac expressions of FGF23 and RAAS-related factors were evaluated, and cardiac histological analyses were performed. In the second experiment, the sham and TAC groups were treated with vehicle, angiotensin-converting enzyme (ACE) inhibitor, or FGF receptor 4 (FGFR4) inhibitor and then evaluated in the same way as in the first experiment. In the early stage of LVH without chronic kidney disease, serum FGF23 levels did not change but cardiac FGF23 expression significantly increased along with LVH progression. Moreover, serum aldosterone and cardiac ACE levels were significantly elevated, and cardiac ACE2 levels were significantly decreased. ACE inhibitor did not change serum FGF23 levels but significantly decreased cardiac FGF23 levels with improvements in LVH and RAAS-related factors, while FGFR4 inhibitor did not change the values. Not serum FGF23 but cardiac FGF23 levels and RAAS parameters significantly changed in the early stage of LVH without chronic kidney disease. RAAS blockade might be more crucial than FGF23 blockade for preventing LVH progression in this condition.

Electrocardiogram evolution in Anderson-Fabry disease patients during follow-up

Abstract Background Anderson-Fabry disease (AFD) is a rare and progressive X-linked metabolic disorder caused by mutations in alfa galactosidase A gene, which leads to a pathologic, multiorgan, accumulation of ceramides with cytotoxic, proinflammatory and fibrotic effects. Cardiovascular involvement represents one of the main causes of death. Although ECG has proven to be useful for early AFD recognition, little evidence is available on the evolution of ECG alterations during follow-up. Purpose and Methods The aims of the study were to describe ECG changes during a long-term follow up, and to evaluate their association with the progression of cardiac involvement. The presence of interactions between ECG changes and specific AFD therapy (treatment status) were also evaluated. 219 AFD patients from a multicentre cohort underwent 12-lead ECG extensive analysis, transthoracic echocardiography, and complete clinical evaluation. Results After the exclusion of 3 patients with a permanent pacemaker, 5 with poor ECG quality, 2 with only one ECG, and 18 ≤18 years old, 181 AFD patients composed the final cohort (age 46 [IQR 35-58], 36% male, 67% classic phenotype). Treatment status (either enzyme replacement or chaperone molecules) was distributed as follows: chronic therapy for at least one year (24%), specific therapy started during the follow up (39%), no specific therapy (37%). During a median follow up of 62 months (IQR 33-83 months), several ECG parameters showed significant changes: atrial fibrillation detection (p&amp;lt;0.001), PQ interval (p=0.004), left atrial enlargement (p=0.001), a new right bundle branch block (RBBB, p&amp;lt;0.001), QRS interval (p&amp;lt;0.001) and QRS fragmentation (p=0.022), QTcB interval (p=0.001), and negative T waves development (p=0.001) mostly lateral and symmetric (p=0.016). Among these, PQ interval showed a significant interaction with treatment status being significantly altered only in patients in the chronic therapy and no specific therapy groups, being stable in patients who started the specific therapy during the follow up (p for interaction=0.048). In addition, PQ, QRS interval duration, a new RBBB, and a new pathologic QT interval were associated with the evolution of the echocardiographic maximal left ventricular (LV) wall thickness during the follow up on univariable analysis, with the QRS duration losing the statistical significance on multivariable analysis but still showing a trend (p=0.089) toward an association with an increased LV wall thickness. Conclusions In this multicentric cohort of AFD patients, different ECG parameters underwent significant changes during follow-up. Of these, PQ interval duration showed a significant interaction with the specific therapy status in that it did not increase in patients who started the therapy at the begin of the follow up. PQ interval, a new RBBB and pathologic QTc development were also significantly associated with the progression of LV hypertrophy on multivariable analysis.Table 1 and Table 2Figure 1

Clinical study of left ventricular structure and function in patients with Anderson-Fabry disease before and after enzyme replacement therapy.

Cardiac left ventricular hypertrophy (LVH) is the most common manifestation of heart involvement in Anderson-Fabry disease (AFD). Conventional cardiac imaging is not sensitive enough to detect early signs of LVH in AFD. It remains uncertain whether enzyme replacement therapy (ERT) can prevent LVH progression and improve myocardial function. This study aimed to assess the effectiveness of two-dimensional speckle tracking echocardiography (2D-STE) in early detection of cardiac involvement in AFD and monitoring the efficacy of agalsidase alfa and agalsidase beta therapy. Thirteen consecutive AFD patients and 12 healthy controls underwent standard transthoracic 2D, color Doppler, tissue Doppler echocardiography, and 2D strain analysis. Global longitudinal strain (GLS) and global circumferential strain (GCS) were measured. Diastolic strain rate (SR) was extracted. Compared to healthy subjects, AFD patients without LVH showed lower levels of GLS (p < 0.001) and SR (p = 0.01), while there was no difference in GCS (p = 0.82). Following treatment, apical circumferential strain (ACS) showed improvement (p = 0.01). In AFD patients without LVH, there was a decrease in global and segmental LS. Higher plasma Lyso-GL-3 concentrations were associated with elevated ACS values after ERT, indicating that ACS in AFD patients without LVH, albeit normal, is involved in early LV dysfunction.

Influence of hypertension and global or abdominal obesity on left ventricular hypertrophy: A cross-sectional study.

Although hypertension and obesity are both risk factors for left ventricular hypertrophy (LVH), the extent of their impact on LVH in the general population is still unclear, and the predictive value of obesity indicators for LVH remains to be elucidated. In this study, obesity-related indicators, including waist circumference (WC), waist-height ratio (WHTR), and waist-hip ratio (WHR), were used to define abdominal obesity (AO), whereas body mass index (BMI) was used to measure general obesity (GO). The effects of hypertension and obesity on LVH were estimated using logistic regression analysis, as was the relative risk of LVH based on the presence of obesity, hypertension, or both. Subgroup analyses were performed based on sex and age. Of the 9134 participants (≥35 years old), 915 (10.0%) developed LVH. After adjusting for covariates, the odds ratios (95% confidence intervals) for LVH were 3.94 (3.27-4.75) in patients with hypertension, 1.90 (1.60-2.26) in those with GO, and 1.45 (1.25-1.69), 1.69 (1.43-2.00), and 1.54 (1.33-4.75) in individuals with AO defined based on WC, WHTR, and WHR, respectively. Analysis by sex showed similar values in women, but AO based on WC and WHR were not significantly associated with LVH in men. Further, after adjusting for potential confounding factors, concomitant hypertension and obesity had an increased risk of developing LVH in all age ranges, particularly in patients aged 35-45 years (risk increased 14.14-fold, 10.84-fold, 7.97-fold, and 9.95-fold for BMI-based GO and WC-, WHTR-, and WHR-based AO, respectively), and in both men and women but particularly in men (risk increased 7.71-fold, 4.67-fold, 5.83-fold, and 5.58-fold, respectively). In summary, all obesity indicators (BMI, WC, WHTR, and WHR) had predictive value for LVH in women; however, only BMI and WHTR should be considered for men. Furthermore, monitoring for the occurrence and progression of LVH is imperative for rural Chinese patients with concomitant hypertension and obesity, especially men and those aged 35-45 years.

Plasma fibrinogen: a driver of left ventricular remodeling in patients undergoing peritoneal dialysis and its related risk factors

Background and aim Plasma fibrinogen has been proven to be significantly associated with cardiovascular mortality in patients undergoing peritoneal dialysis (PD). The study aimed to investigate the role of fibrinogen in left ventricular (LV) remodeling and functions in patients on PD, and explore risk factors related to high fibrinogen level. Methods From February 2008 to July 2018, adult patients on regular PD for at least 1 month were recruited and followed up for two years. Correlation analysis was performed to explore the fibrinogen level and echocardiography measurements. Pathogenic factors correlated to the left ventricular hypertrophy (LVH) progression were explored by logistic regression models and the role of fibrinogen in it was verified by receiver operating characteristic (ROC) curves. Linear regression models were conducted to identify factors associated with fibrinogen level. Results A total of 278 patients undergoing PD (168 males, 60.4%) were recruited. Patients were trisected according to fibrinogen levels at baseline. Mean wall thickness (MWT), relative wall thickness (RWT), and left ventricular mass index (LVMI) were positively associated with fibrinogen level while E/A ratio was negatively associated with it. Multivariate logistic regression and ROC curve showed that fibrinogen was an independent risk factor for LVH progression. Multivariate linear regression analysis identified age, total cholesterol (CHO), fasting blood glucose (FBG), and high-sensitivity C-reactive protein (hsCRP) were significantly related to plasma fibrinogen level. Conclusions An elevated fibrinogen level was independently associated with LVH progression in patients undergoing PD. Older age, higher level of FBG, CHO, and hsCRP were risk factors for elevated plasma fibrinogen level.

Delayed-release rapamycin halts progression of left ventricular hypertrophy in subclinical feline hypertrophic cardiomyopathy: results of the RAPACAT trial.

Feline hypertrophic cardiomyopathy (HCM) remains a disease with little therapeutic advancement. Rapamycin modulates the mTOR pathway, preventing and reversing cardiac hypertrophy in rodent disease models. Its use in human renal allograft patients is associated with reduced cardiac wall thickness. We sought to evaluate the effects of once-weekly delayed-release (DR) rapamycin over 6 months on echocardiographic, biochemical, and biomarker responses in cats with subclinical, nonobstructive HCM. 43 client-owned cats with subclinical HCM. Cats enrolled in this double-blinded, multicentered, randomized, and placebo-controlled clinical trial were allocated to low- or high-dose DR rapamycin or placebo. Cats underwent physical examination, quality-of-life assessment, blood pressure, hematology, biochemistry, total T4, urinalysis, N-terminal pro-B-type natriuretic peptide, and cardiac troponin I at baseline and days 60, 120, and 180. Fructosamine was analyzed at screening and day 180. Echocardiograms were performed at all time points excluding day 120. Outcome variables were compared using a repeated measures ANCOVA. No demographic, echocardiographic, or clinicopathologic values were significantly different between study groups at baseline, confirming successful randomization. At day 180, the primary study outcome variable, maximum LV myocardial wall thickness at any location, was significantly lower in the low-dose DR rapamycin group compared to placebo (P = .01). Oral DR rapamycin was well tolerated with no significant differences in adverse events between groups. Results demonstrate that DR rapamycin was well tolerated and may prevent or delay progressive LV hypertrophy in cats with subclinical HCM. Additional studies are warranted to confirm and further characterize these results.

Distinguishing left ventricular hypertrophy from hypertrophic cardiomyopathy in adolescents - a longitudinal observation study

Abstract Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): MF: The South-Eastern Norway Regional Health Authority [grant number 2017207]. KHH, MKS: Norwegian Research Council [grant number 309762 ProCardio]. Background Distinguishing athlete´s heart from hypertrophic cardiomyopathy (HCM) can be challenging. There is a lack of data describing physiological and pathological remodelling in adolescents. Purpose The purpose of this study was to compare development of left ventricular (LV) hypertrophy in adolescent athletes to HCM genotype positive adolescents. Methods Athletes and age- and sex-matched HCM genotype positive adolescents underwent echocardiography at baseline and at follow-up, minimum two years later. Echocardiographic parameters were evaluated by pediatric reference values (Z-scores). LV hypertrophy was defined as Z-score &amp;gt;2 for intraventricular septum diameter (IVSd) or posterior wall thickness (LVPWd). Results Seventy-six athletes were compared to 63 (1 proband, 62 family members) HCM genotype positive adolescents (37% vs 44% female, p = 0.36, mean age baseline 12.1±0.2 vs 12.4±1.4 years, p = 0.10). Mean follow-up-time was alike by protocol (3.1±0.2 vs 3.2±1.3 years, p = 0.59). LV hypertrophy was found in a similar proportion of athletes and HCM genotype positive adolescents (28% vs 30% at baseline, p = 0.75, 30% vs 32% at follow-up, p = 0.80). Compared with athletes, interventricular septum was thicker in HCM genotype positive adolescents at baseline (Z IVSd 1.4±0.9 vs 2.7±5.2, p = 0.03). Left ventricular volumes were greater in athletes (Z LVEDV 1.0±0.6 vs −0.1±0.9, p&amp;lt;0.001). Septum thickness increased only in HCM genotype positive adolescents (Z IVSd progression rate −0.17(SE0.05), p = 0.001 vs 0.54(SE0.16), p = 0.001, p for interaction &amp;lt;0.001). There was no difference in LVPWd (0.6±1.3 vs 0.8±0.8, p = 0.13). Conclusions LV hypertrophy was observed in nearly 1/3 of both athletes and HCM genotype positive adolescents in the first longitudinal study comparing these populations. We found a significant difference in progression of LV hypertrophy, with increasing septum thickness only in the HCM genotype positive adolescents. These findings highlight the importance of repeated examinations to distinguish physiological from pathological remodelling.

#3579 AN INITIAL LOW-DOSE ETELCALCETIDE APPROACH IS EFFECTIVE AND COST-SAVING IN HEMODIALYSIS PATIENTS WITH MODERATE SECONDARY HYPERPARATHYROIDISM

Abstract Background and Aims Etelcalcetide (ETC) is an intravenous calcimimetic approved for the management of secondary hyperparathyroidism (sHPT) in hemodialysis (HD) patients, with benefits in terms of reduction of FGF23 levels and prevention of progression of left ventricular hypertrophy. The label recommendation is a starting dose of 5 mg after HD, to be titrated every 4 weeks according to parathyroid hormone (PTH) and calcium levels. However, it remains unclear what dosage is best to start with and, thus, how this treatment can be implemented in a real-life setting. The aim of this study was to assess the efficacy and cost-effectiveness of ETC started at lower doses than those suggested by the manufacturer in patients with moderate sHPT. Methods This is a retrospective observational study comparing two different initial ETC dosing strategies, a “Low-dose approach” (LD, ETC starting dose&amp;lt;10 mg/week) and a “Classic approach” (CL, ETC starting dose≥10 mg/week), in terms of effects on CKD-MBD related biomarkers and costs during the first year of prescription. The study was conducted on HD patients with basal PTH between 500 and 1500 ng/l, treated with ETC for at least 3 months between 2018 and 2022 at ASST Spedali Civili di Brescia. Monthly monitoring of serum calcium, phosphorus and PTH was performed in both groups for dose adjustment. Results Overall, 53 patients were identified, 24 in the LD and 29 in the CL group. Both groups showed similar baseline characteristics (Table 1). Median follow-up was 52 weeks, during which 4 patients (one in the LD and three in the CL group) discontinued ETC (Table 1). At the end of follow-up, 92% of patients in the LD and 90% in the CL group achieved a decrease in PTH ≥30% compared to baseline, with median PTH levels of 282 (207 - 332) and 294 (151 – 382) ng/l, respectively (p = 0.825). Other CKD-MBD biochemical parameters were comparable between the two groups at all timepoints (Figure 1). The median of average ETC weekly doses per patient was 7.6 (6.2 – 10.2) mg in the LD and 10.6 (9.7 – 15) mg in the CL group (p&amp;lt;0.001). During follow-up, the median ETC dose remained stable in the LD group, while partially decreasing in the CL group (Figure 1). Use of paricalcitol was comparable in both groups. At cost analysis, the median of average ETC weekly costs per patient was €36.6 (29.6 – 50.0) in the LD and €50.5 (46.4 – 71.7) in the CL group (p&amp;lt;0.001). This translates into an average yearly cost per patient of €1909 and €2635 using the LD and CL approach, respectively, with a saving of €726 per patient-year in favour of the LD strategy. Conclusion In this retrospective study in HD patients with moderate sHPT, we showed that starting ETC at a lower dose than the one suggested by the manufacturer is as effective as the classic approach in terms of control of CKD-MBD parameters, with a significant reduction in treatment costs. Future prospective studies will be needed to validate the results in bigger cohorts, test whether these benefits can extend beyond the first year of treatment and assess the effects on FGF23 levels and other relevant clinical outcomes.

Rapid progression of left ventricular hypertrophy caused by leukaemic infiltration of myocardium.

A man in his 40s was hospitalized due to recurrence of acute myeloid leukaemia. Echocardiography was performed because of negative T waves in the electrocardiogram. Severe and global left ventricular hypertrophy (LVH) was observed (Panels B and E, see Supplementary data online, Video S2), which was not found 15 months ago (Panels A and D, Supplementary data online, Video S1). Computed tomography scan also showed severe LVH (Panel H), which was not found 3 months ago (Panel G). Thus, it was confirmed that the rapid hypertrophic change occurred within 3 months. Low-dose Ara-C (cytosine arabinoside) and VP-16 (etoposide) therapy was administered for leukaemia. Echocardiography, after two weeks from the start of treatment, showed reduced LVH (Panels C and F). Therefore, the myocardial infiltration of leukaemia cells was considered as the cause of LVH. Unfortunately, 16 weeks later, the patient died by multiple organ failure. Autopsy showed that the cardiac wall thickened and numerous numbers of leukaemia cells infiltrated in the myocardium (Panels J and K). Distribution of the myocardial fibre was disarrayed but necrosis was not found. Infiltration of leukaemia cells was observed in multiple organs.

Lessons from effect of etelcalcetide on left ventricular hypertrophy in patients with end-stage kidney disease.

Purpose of reviewPatients with end-stage kidney disease (ESKD) frequently develop left ventricular hypertrophy (LVH), which is associated with an exceptionally high risk of cardiovascular events and mortality. This review focuses on interventional studies that modify levels of fibroblast growth factor 23 (FGF23) and examine effects on myocardial hypertrophy, cardiovascular events and mortality.Recent findingsQuantitative evaluations of trials of calcimimetics found no effects on cardiovascular events and cardiovascular and all-cause mortality when compared with placebo. However, a recent randomized, controlled trial of etelcalcetide versus alfacalcidol showed that etelcalcetide effectively inhibited the progression of LVH in comparison to vitamin D in patients on haemodialysis after 1 year of treatment. Prior to that, oral calcimimetic treatment has already been shown to reduce left ventricular mass in patients on haemodialysis, whereas treatment with active vitamin D or mineralocorticoids was ineffective in patients with ESKD.SummaryData from a recent trial of etelcalcetide on LVH suggest that FGF23 may be a possible therapeutic target for cardiac risk reduction in patients on haemodialysis. If these findings are confirmed by further research, it might be speculated that a treatment shift from active vitamin D towards FGF23-lowering therapy may occur in patients on haemodialysis.

The Correlation Between ABPM Parameters and Left Ventricular Hypertrophy in Pediatric Essential Hypertension.

ObjectiveTo explore the association of dipping pattern and blood pressure load with left ventricular hypertrophy (LVH) in pediatric essential hypertension.Materials and MethodsThrough an echocardiography monitor and an ambulatory blood pressure monitor of 425 children and adolescents diagnosed with essential hypertension with no treatment received, we identified 140 cases of LVH. Grouping patients according to LVH (LVH, N = 140; n-LVH, N = 285), we further evaluated their ambulatory blood pressure monitoring (ABPM) parameters by comparing dipping patterns between groups. A multivariable logistic regression analysis was used to determine the effect of blood pressure load on LVH.ResultsNo significant difference was found in systolic or diastolic blood pressure dipping patterns between groups (P = 0.161, P = 0.139). However, compared to the n-LVH group, the LVH group presented significant elevated nighttime systolic blood pressure (SBP) (P < 0.05), while nighttime DBP remained stable (P = 0.391), resulting in higher daytime and nighttime SBP loads, higher nighttime DBP load, and higher 24-h SBP load (P < 0.05). Notably, our multivariable logistic regression has shown that this trend of 24-h SBP load acts independently as a critical risk factor for LVH.ConclusionCollectively, we observed a correlation between BP load and LVH in pediatric hypertension. Our data demonstrated that SBP load has a more significant weight in LVH progression, and 24-h SBP load, in particular, acts as a critical early prognostic parameter for LVH in pediatric hypertension.

The Effect of FGF23 on Cardiac Hypertrophy Is Not Mediated by Systemic Renin-Angiotensin- Aldosterone System in Hemodialysis

Fibroblast growth factor 23 (FGF23) is elevated in patients with chronic kidney disease and contributes to left ventricular hypertrophy (LVH). The aim of the analysis was to determine whether this effect is mediated by the renin-angiotensin-aldosterone system (RAAS) in hemodialysis. Serum samples from 62 randomized hemodialysis patients with LVH were analyzed for plasma renin activity (PRA-S), angiotensin II (AngII), and metabolites, angiotensin-converting enzyme-2 (ACE2) and aldosterone using a high throughput mass spectrometry assay. Compared to healthy individuals, levels of the RAAS parameters PRA-S, AngII and aldosterone were generally lower [median (IQR) PRA-S 130 (46–269) vs. 196 (98, 238) pmol/L; AngII 70 (28–157) vs. 137 (76, 201) pmol/L; Aldosterone 130 (54, 278) vs. 196 (98, 238) pmol/L]. We did not find an indication that the effect of FGF23 on LVH was mediated by RAAS parameters, with all estimated indirect effects virtually zero. Furthermore, FGF23 was not associated with RAAS parameter levels throughout the study. While there was a clear association between FGF23 levels and left ventricular mass index (LVMI) at the end of the study and in the FGF23 fold change and LVMI change analysis, no association between RAAS and LVMI was observed. Serum concentrations of PRA-S, AngII, and aldosterone were below the ranges measured in healthy controls suggesting that RAAS is not systemically activated in hemodialysis patients. The effect of FGF23 on LVMI was not mediated by systemic RAAS activity. These findings challenge the current paradigm of LVH progression and treatment with RAAS blockers in dialysis.Clinical Trial Registration[https://clinicaltrials.gov/ct2/show/NCT03182699], identifier [NCT03182699].

Abstract P111: Differentially Methylated DNA Regions In Left Ventricular Hypertrophy: A HyperGEN Study

Left ventricular (LV) hypertrophy (LVH) is an independent risk factor for cardiovascular morbidity and mortality that is commonly associated with hypertension. African Americans (AAs) experience an especially high risk of LVH. Genomic studies have identified potential candidate genes associated with LVH, but more research is needed to further explain the high estimated heritability for these traits in AAs. Epigenetic modifications, such as DNA methylation, may account for the unexplained heritability in LVH in AAs. In this study, we used epigenotype and echocardiography data from 636 African Americans selected from the Hypertension Genetic Epidemiology Network (HyperGEN) to identify differentially methylated regions (DMRs) of DNA in association with LV related traits. DNA was isolated from participants’ whole blood, and more than 485,000 CpGs were assayed on Illumina Methyl450K arrays. Linear mixed models were used to test the association between a DMR and LV trait using the coMethDMR package in R. We identified several DMRs associated with LV traits in HyperGEN. There was an association between methylation of XKR6 and ejection fraction (β[SE]:0.005[0.001], FDR: 0.056), as well as TRAK1 and LV internal diastolic dimension (β[SE]:0.113[0.027], FDR: 0.042). There was also an inverse relationship between LV mass indexed to height and methylation of GSE1 (β[SE]:-0.002[0.001], FDR: 0.085), RPS15A (β[SE]:-0.002[0.001], FDR: 0.085), and PSMD7 (β[SE]:-0.003[0.001], FDR: 0.085). Additionally, relative wall thickness was inversely associated with a DMR annotated to DNHD1 (β[SE]:-1.269[0.275], FDR: 0.008). Methylation variations of GSE1 , PSMD7 , and DNHD1 have previously been linked to cardiac structural function, and external validation of these findings is in progress. In summary, differentially methylated regions of DNA may help explain additional variation in LVH-related traits and heritability in AAs. Future studies should evaluate potential relationships between regional DNA methylation patterns and the development and progression of LVH.

Association between atherogenic index of plasma and left ventricular hypertrophy in patients with chronic heart failure with mid-range ejection fraction

Aim: The aim of the present study was to investigate whether an association between lipid indices- atherogenic index of plasma (AIP), Castelli Risk Index I (CRI-I), Castelli Risk Index II (CRI-II) and triglyceride index (TGL-index) and the development of left ventricular hypertrophy exists in patients with heart failure with mid-range ejection fraction (HFmrEF). Material and methods: The study involved 56 patients with HFmrEF and normal lipid profile, median age 64 (47-84) and 22 healthy subjects, median age 58 (51-69). The patients were divided in two subgroups: subjects with left ventricular hypertrophy (n=32); (HFmrEF+LVH) and subjects without left ventricular hypertrophy (n=24); (HFmrEF-LVH). The lipid profile was measured by laboratory, while lipid indices were calculated, using the established formulas. Results: There was not statistically significant difference between the lipid indices in patients with heart failure with mid-range ejection fraction compared to healthy controls (p&amp;gt;0.05). HFmrEF+LVH patients showed statistically significantly higher values of atherogenic index of plasma than HFrEF-LVH patients: 0.16 (0.05/0.37) vs. 0.04 (0.01/0.11); (KW=5.80; p=0.02). TC/HDL, LDL/HDL and TG/HDL values were not significantly higher in HFmrHEF+LVH than HFmrEF-LVH patients: 4.8 (3.98/5.75) vs. 4.49 (3.58/5.63); 2.91 (2.1/4.0) vs. 2.9 (2.5/4.25) and 1.36 (1.11/2.08) vs. 1.13 (0.9/1.53), respectively (p&amp;gt;0.05). No significant gender differences between lipid indices were found. Atherogenic index of plasma showed correlation with LVH (r=0.45; p=0.01) and interventricular septum thickness (r=0.55; p=0.002). Conclusion: Our findings show an association between atherogenic index of plasma and LVH in patients with HFmrEF with normal lipid profile. Further studies are warranted to confirm whether determination of AIP may be used for monitoring development and progression of left ventricular hypertrophy in heart failure with mid-range ejection fraction.

Physiological, Pathological and Pharmacological Interactions of Hydrogen Sulphide and Nitric Oxide in the Myocardium of Rats with Left Ventricular Hypertrophy.

Left ventricular hypertrophy (LVH) is characterized by increased myocardium thickness due to increased oxidative stress and downregulation of cystathione γ lyase (CSE) endothelial nitric oxide synthase (eNOS). Upregulation of CSE by hydrogen sulphide (H2S) and ENOS by L-arginine can arrest the progression of LVH individually. The present study explored the combined treatment of H2S and NO in the progression of LVH, and demonstrated that the response is due to H2S, NO or formation of either new molecule in physiological, pathological, and pharmacological in vivo settings of LVH. Exogenous administration H2S+NO in LVH significantly reduced (all p < 0.05) systolic blood pressure (SBP) and mean arterial pressure (MAP), LV index, heart index and oxidative stress when compared to the LVH group. There was downregulation of CSE mRNA and eNOS in the heart, and exogenous administration of H2S+NO groups upregulated eNOS MRNA while CSE MRNA remained downregulated in the hearts of the LVH group. Similar trends were observed with concentrations of H2S and NO in the plasma and tissue. It can be concluded that combined treatment of LVH with H2S and NO significantly ameliorate the progression of LVH by attenuating systemic hemodynamic and physical indices, and by decreasing oxidative stress. Molecular expression data in the myocardium of LVH depicts that combined treatment upregulated eNOS/NO while it downregulated CSE/H2S pathways in in vivo settings, and it is always eNOS/NO pathways which play a major role.

Pseudo-electrocardiographic regression of left ventricular hypertrophy in aortic stenosis: concomitant cardiac amyloidosis

A 78-year-old woman was followed up on diagnosis with mild aortic stenosis (AS) 20 years ago. In 2002, the voltage of the R wave in her electrocardiography (ECG) was normal (Panel A). In 2015, echocardiography revealed the peak velocity across the aortic valve increased to up to 3.4 m/s, and she was diagnosed with mild left ventricular hypertrophy (LVH) (Panel B). Her ECG gradually showed a high voltage, reflecting the progression of LVH due to AS (Panel A). In 2018, the voltage of SV1+RV5 (Sokolow–Lyon index) increased from 2.3 mV to 4.3 mV in synchronization with the ongoing LVH (Panel C). However, the voltage started to decrease from 2019. In 2021, the voltage of SV1+RV5 finally reduced to 2.5 mV, and the patient was hospitalized due to heart failure despite AS severity remained moderate. For the limb leads, the voltage of lead III continuously decreased from the beginning of the follow-up, and a pseudo-infarct pattern was observed in 2021 (Panel A). The apical sparing pattern (Panel D) and the findings of Tc99m-pyrophosphate scintigraphy (Panel E) were consistent with cardiac amyloidosis. Based on these findings, we determined that she had transthyretin cardiac amyloidosis combined with AS.

Randomized Trial of Etelcalcetide for Cardiac Hypertrophy in Hemodialysis.

[Figure: see text].

Reversible Treatment of Pressure Overload-Induced Left Ventricular Hypertrophy through Drd5 Nucleic Acid Delivery Mediated by Functional Polyaminoglycoside.

Left ventricular hypertrophy and fibrosis are major risk factors for heart failure, which require timely and effective treatment. Genetic therapy has been shown to ameliorate hypertrophic cardiac damage. In this study, it is found that in mice, the dopamine D5 receptor (D5R) expression in the left ventricle (LV) progressively decreases with worsening of transverse aortic constriction‐induced left ventricular hypertrophy. Then, a reversible treatment of left ventricular hypertrophy with Drd5 nucleic acids delivered by tobramycin‐based hyperbranched polyaminoglycoside (SS‐HPT) is studied. The heart‐specific increase in D5R expression by SS‐HPT/Drd5 plasmid in the early stage of left ventricular hypertrophy attenuates cardiac hypertrophy and fibrosis by preventing oxidative and endoplasmic reticulum (ER) stress and ameliorating autophagic dysregulation. By contrast, SS‐HPT/Drd5 siRNA promotes the progression of left ventricular hypertrophy and accelerates the deterioration of myocardial function into heart failure. The reduction in cardiac D5R expression and dysregulated autophagy are observed in patients with hypertrophic cardiomyopathy and heart failure. The data show a cardiac‐specific beneficial effect of SS‐HPT/Drd5 plasmid on myocardial remodeling and dysfunction, which may provide an effective therapy of patients with left ventricular hypertrophy and heart failure.