Degree Of Left Ventricular Hypertrophy Research Articles

Epigenetic Study of Cohort of Monozygotic Twins With Hypertrophic Cardiomyopathy Due to MYBPC3 (Cardiac Myosin-Binding Protein C).

Hypertrophic cardiomyopathy is an autosomal dominant cardiac disease. The mechanisms that determine its variable expressivity are poorly understood. Epigenetics could play a crucial role in bridging the gap between genotype and phenotype by orchestrating the interplay between the environment and the genome regulation. In this study we aimed to establish a possible correlation between the peripheral blood DNA methylation patterns and left ventricular hypertrophy severity in patients with hypertrophic cardiomyopathy, evaluating the potential impact of lifestyle variables and providing a biological context to the observed changes. Methylation data were obtained from peripheral blood samples (Infinium MethylationEPIC BeadChip arrays). We employed multiple pair-matched models to extract genomic positions whose methylation correlates with the degree of left ventricular hypertrophy in 3 monozygotic twin pairs carrying the same founder pathogenic variant (MYBPC3 p.Gly263Ter). This model enables the isolation of the environmental influence, beyond age, on DNA methylation changes by removing the genetic background. Our results revealed a more anxious personality among more severely affected individuals. We identified 56 differentially methylated positions that exhibited moderate, proportional changes in methylation associated with left ventricular hypertrophy. These differentially methylated positions were enriched in regions regulated by repressor histone marks and tended to cluster at genes involved in left ventricular hypertrophy development, such as HOXA5, TRPC3, UCN3, or PLSCR2, suggesting that changes in peripheral blood may reflect myocardial alterations. We present a unique pair-matched model, based on 3 monozygotic twin pairs carrying the same founder pathogenic variant and different phenotypes. This study provides further evidence of the pivotal role of epigenetics in hypertrophic cardiomyopathy variable expressivity.

High-intensity exercise-related sudden cardiac death in hypertrophy cardiomyopathy

Abstract Background Whether exercise provokes sudden cardiac death (SCD) in patients with hypertrophic cardiomyopathy (HCM) is uncertain. Current European guidelines recommend against high-intensity exercise in individuals with high SCD risk or obstructive physiology. Purpose We investigated the factors associated with exercise-related SCD in HCM. Methods We retrospectively analyzed of 2,844 consecutive patients with HCM who underwent evaluation between 2005 and 2023 at a high-volume tertiary center. SCD events were defined as a composite of aborted SCD, appropriate implantable cardioverter-defibrillator (ICD) shock, and SCD. Among 80 first SCD events (2.8%), 75 events had a description of the physical activity at the time of the event. Patients were classified into two groups according to physical activity level at the time of the SCD event. Group 1 included patients with high-intensity exercise-related SCD events, defined as happening during or immediately after high-intensity exercise or physical activity, while Group 2 included patients with SCD events happening at rest or during light or moderate physical activity. Results The 75 first SCD events included 44 aborted SCD, 22 appropriate ICD shocks, and 9 SCD. Median age at SCD event was 54 (IQR 39.5–62.5) years and 60 (80%) were men. Patients in Group 1 (n=14) were younger than patients in Group 2 (n=61) (23.5 [IQR 16–48] vs. 55 [IQR 44–64] years, p<0.001), and most patients in group 1 (92.9%) were under the age of 60 years. Patients in Group 1 had slightly smaller left ventricular (LV) end-diastolic dimension and had higher ESC SCD risk scores (3.6 [IQR 2.5–6.7] vs. 2.4 [IQR 1.7–4.8], p=0.044) than patients in Group 2; however, there were no significant differences in the proportion of high-risk patients (28.6% vs. 14.8%, p=0.396) or patients with AHA major SCD risk factors (57.1% vs. 55.7%, p=0.999). Otherwise, there were no significant differences in the presence of obstructive physiology, apical HCM, and apical aneurysm, LV systolic and diastolic function, and comorbidities between the two groups. Furthermore, of the 29 patients who underwent genetic testing, there was no difference in the proportion of patients with pathogenic sarcomeric variants according to exercise-related SCD (50.0% vs. 65.2%, p=0.683). To note, there was a non-significant tendency towards higher proportion of thin filament variants in Group 1 than Group 2 among those with pathogenic sarcomeric variants (100% [3/3] vs 26.7% [4/15], p=0.084). Conclusions Most high-intensity exercise-related SCD events happened under the age of 60. The ESC SCD risk score was higher in patients with high-intensity exercise-related SCD events, although the SCD risk categories or AHA risk factors could not discriminate patients at higher risk of events. These results suggest that exercise recommendations should not be based on SCD risk category, presence of obstruction, or degree of LV hypertrophy.

Cardiovascular magnetic resonance insights into anomalies of the mitral valve apparatus in Fabry cardiomyopathy and hypertrophic cardiomyopathy.

Despite different etiopathogenesis, Fabry Disease cardiomyopathy (FDc) and sarcomeric hypertrophic cardiomyopathy (HCM) share a similar hypertrophic phenotype, including anomalies of the mitral valve apparatus (AMVA). Some of these anomalies have also been described in the pre-hypertrophic stage of both diseases. This cardiovascular magnetic resonance (CMR) study aimed to: (i) compare AMVA between FDc and HCM with a similar degree of left ventricular hypertrophy (LVH), to add new insights into differential diagnosis; (ii) assess whether AMVA represent an early and progressive alteration in FDc; (iii) propose simple and potentially reproducible measurements of AMVA. This observational, retrospective study enrolled: (i) 80 Fabry patients, divided into three groups with increasing severity of cardiac phenotype (20 patients LVH-/normal T1, 20 patients LVH-/low T1 and 40 patients LVH+), and (ii) 40 patients with HCM. All patients underwent CMR. The LVH + FDc and the HCM groups were matched for age, sex, body surface area and left ventricular (LV) mass. The following AMVA were measured on cine images: papillary muscles (PMs) hypertrophy (maximal diameter (Dmax) of anterolateral (Al) and posteromedial (Pm) PM), apical displacement, anteriorization of Al PM and anterior mitral valve leaflet (AMVL) elongation. Reference values for defining AMVA were derived from a matched healthy control group (n = 40). Both HCM and FDc LVH + patients showed PMs hypertrophy, with a greater degree in the FDc LVH + group [Dmax Al PM 16 ± 3.4 vs. 15 ± 3.1 mm, p 0.017; Dmax Pm PM 14 ± 4.0 vs.12 mm (10.0-14.0), p 0.039] As compared to controls, both HCM and FDc LVH + patients showed PMs apical displacement (HCM 83% vs. healthy volunteers 8%, p < 0.001; FDc LVH + 65% vs. healthy volunteers 8%, p < 0.001), with a greater prevalence in HCM. Anteriorization of Al PM was only evident in HCM (15 ± 6.2 vs. healthy controls 21 ± 5.3 mm, p < 0.001). Elongation of AMVL was detected both in HCM and FDc with LVH + (HCM 29 ± 4.0 vs. healthy volunteers 24 ± 2.9 mm, p < 0.001; FDc LVH + 27 ± 4.0 vs. healthy volunteers 24 ± 2.9 mm, p < 0.001) without significant differences between the two phenocopies. The prevalence of myocardial crypts was higher among HCM patients than in FDc LVH + patients (75% vs. 48%, p 0.012). we report greater PMs hypertrophy in FDc and a higher prevalence of PMs positional alterations (anterior and apical displacement) and myocardial crypts in HCM. All these AMVA became more pronounced with the progression of the FDc phenotype. We suggest the systematic inclusion of the analysis of AMVA by simple linear measurements on cine images in the CMR assessment of hypertrophic cardiomyopathies, to help in the differential diagnosis between HCM and FDc and to facilitate early detection of cardiac involvement in FDc.

A case report of critical aortic stenosis diagnosed utilizing non-imaging continuous wave Doppler probe

Abstract Background Aortic stenosis (AS) is the most commonly acquired valvular pathology in the western world. Aortic stenosis severity is typically evaluated with Doppler echocardiography. Evaluation of aortic gradients using standard Doppler echocardiography from the apical window may underestimate the true gradient due to misalignment of blood flow to the ultrasound beam and is often better evaluated from other imaging windows using a non-imaging continuous wave Doppler (NI-CWD) probe. Herein, we describe a unique case of AS being underestimated by dynamic acoustic shadowing from the apical window rather than beam misalignment. Case summary The patient is a Hispanic 31-year-old male with a congenital bicuspid aortic valve who underwent a balloon aortic valvuloplasty at age 13. At age 31, the patient underwent a repeat transthoracic echocardiogram (TTE) that was largely unchanged from his prior TTE from 15 years prior. Notably on this TTE, there was acoustic shadowing of colour Doppler in the distal left ventricular outflow tract and aortic valve during systole. While gradients only suggested moderate AS, the degree of left ventricular hypertrophy was suspicious for more severe AS. Only by using the NI-CWD probe at the right sternal border were we able to identify very severe AS with a peak velocity of 6.5 m/s and a mean gradient of 100 mmHg. Discussion In our specific case, dynamic acoustic shadowing of the aortic valve from the apical window obscured both imaging and Doppler signals. This acoustic shadowing was not present from the right sternal border with the NI-CWD probe, leading to an over 100% increase in aortic valve peak velocity and proper correction of AS severity. This allowed for expedited care and underscores the importance of such techniques.

Fatty liver as a risk factor for cardiovascular diseases: retrospective analysis of data from patients of the Geriatrics Clinic of University Clinical Hospital in Wrocław

Non-alcoholic fatty liver disease (NAFLD) is currently the most common liver disorder affecting about 25% of the global population. The causes of its development include poor diet, low physical activity, overweight, obesity, older age, diabetes, and lipid disorders. Non-alcoholic fatty liver disease is identified by some researchers as a hepatic manifestation of metabolic syndrome. It has been observed that patients with NAFLD have an increased risk of cardiovascular events, as well as a higher number of deaths from myocardial infarction compared to the general population. A retrospective analysis was conducted on the data of 237 patients diagnosed with hepatic steatosis, treated in the Department of Geriatrics at the University Clinical Hospital in Wrocław from 2019 to 2022, focusing on coexisting overweight, obesity, and concomitant diseases. Laboratory results and the degree of left ventricular muscle hypertrophy were analyzed. Parameters assessed by echocardiography, including interventricular septal thickness in diastole (IVSd), left ventricular posterior wall thickness in diastole (LVPWd), and IVSd + LVPWd/2, were used to evaluate left ventricular hypertrophy. Data from 237 patients were analyzed: 79 men (age: 77.2±7.1 years) and 158 women (age: 78.4±7.7 years). Body mass index (BMI) values for men and women were 30.5±5.0 kg/m² and 31.9±5.6 kg/m², respectively. There was a positive correlation between BMI and the degree of left ventricular hypertrophy for the parameters IVSd (ρ = 0.36, p < 0.001), LVPWd (ρ = 0.36, p < 0.001), and IVSd + LVPWd/2 (ρ = 0.38, p < 0.001). The study demonstrated a moderate positive correlation between BMI and the degree of left ventricular hypertrophy in patients diagnosed with hepatic steatosis. These findings indicate the necessity of actively searching for cardiovascular risk factors, including the evaluation of echocardiographic parameters in patients with NAFLD. Med Pr Work Health Saf. 2024;75(3):223-231.

Myocardial work alterations with progressive left ventricular hypertrophy in patients with hypertension.

Left ventricular (LV) hypertrophy (LVH) is frequently observed in patients with hypertension (HTN). LV myocardial work (MW) has recently emerged as a non-invasive method to assess systolic myocardial deformation relative to afterload conditions. The authors investigated the characteristics of myocardial work with different degrees of LVH in HTN patients. From December 2020 to February 2024, 255 HTN patients and 26 healthy controls undergoing transthoracic echocardiography were included in the current study. Hypertension patients were divided into quintile groups based on left ventricular mass index (LVMI), for the first to fourth LVMI quantiles, global work index (GWI) and global constructive work (GCW) were higher compared to the control group, but the difference was not statistically significant. In the sixth LVMI quantile, GWI and GCW showed a significant decrease. The restricted cubic splines showed that both GWI and GCW exhibited an inverted U-shaped relationship with LVMI. A LVMI of >151.39g/m2 could accurately predict reduction both in GWI and GCW (Sensitivity: 0.78, Specificity: 0.89, AUC: 0.90, P <.001; Sensitivity: 0.81, Specificity: 0.92, AUC: 0.92, P <.001, respectively). As LVH progressed in HTN patients, both GWI and GCW initially demonstrated an increase, followed by a subsequent decrease. Myocardial work provides additional insights into assessment of cardiac function in HTN patients.

A Mutational Hotspot in The LAMP2 Gene: Unravelling Intrafamilial Phenotypic Variation and Global Distribution of The c.877C>T Variant: A Descriptive Study.

Danon disease is defined by a clinical trio of cardiomyopathy, skeletal myopathy, and cognitive impairment. It results from the lysosomal-associated membrane protein-2 (LAMP2) gene variants. The aim of study is determination of genotype and phenotype of a newly diagnosed Iranian family with a unique phenotype due to a pathogenic variant of the LAMP2 gene along with a phenotypic comparison of all reported patients. In this descriptive study, we evaluated the demographic data, clinical features, management procedures, as well as genetic analysis of both patients in this newly diagnosed family. Whole genome sequencing (WGS) and in silico structural and functional predictions were applied. A comprehensive search of the c.877C>T variant in LAMP2 was conducted using the PubMed, Google Scholar, VarSome, ClinVar, Human Gene Mutation Database (HGMD), and Franklin databases to identify any genotype-phenotype correlations. Nine patients were carriers of the c.877C>T variant. All patients were male, and displayed variable degrees of left ventricular hypertrophy (LVH) that ranged from mild to severe. All patients exhibited typical cardiac conduction abnormalities consistent with Danon disease. Four underwent heart transplants and survived. Skeletal muscle involvement and cognitive impairment were observed in four patients each. The mean age of onset was 14 years. The proband in this study exhibited an earlier onset of cardiac symptoms. Genetic analysis is the preferred diagnosis approach for Danon disease and can assist families in managing affected patients, identify carriers, and assist with future family planning. This study highlights the intrafamilial phenotypic variability of Danon disease. It is possible that variants of this gene may be frequent in Iran.

Electrocardiographic evolution in Anderson-Fabry disease: a valuable tool to detect progressive cardiac involvement

Abstract Background Anderson-Fabry disease (AFD) is a multisystemic disorder caused by accumulation of glycosphingolipid in affected tissues and cardiac involvement can manifest with left ventricular hypertrophy (LVH), conduction delays, arrythmias and valvulopathies. Electrocardiogram (ECG) has proven to be useful for early detection of this condition, but there are only few datas on the association between ECG alterations and the progression of the disease. Purpose To evaluate the association between ECG anomalies and progressive cardiac involvement in AFD patients with different degrees of left ventricular hypertrophy. Methods We recruited 189 AFD patients &amp;gt; 18 years old (39% males, median age 47 years, 68% classical AFD) in a multicentre cohort and we divided them into 4 groups according to different degree of left ventricular (LV) thickness: group A ≤ 9mm (n = 52, 28%); group B 10-14 mm (n = 76, 40%); group C 15-19 mm (n = 46, 24%); group D ≥ 20 mm (n = 15, 8%). They underwent a complete clinical, ECG and echocardiographic evaluation and we analysed their ECG features in order to detect patterns suggestive of the different stages of AFD. Results A normal ECG was present in 87% of patients in group A, 54% in group B, 11% in group C, and 7% in group D. The most common conduction delay type was right bundle branch block (RBBB), mainly incomplete in groups B and C (respectively 20% and 22%) and complete RBBB in group D (53%), with p &amp;lt; 0.001; whereas none of the patients had LBBB. The prevalence of LVH criteria showed a statistically significant increase among the groups (p &amp;lt; 0.001) and also negative T waves and ST segment depression were more frequent in group C and D (p &amp;lt; 0.001), involving mainly lateral and inferior leads. Analysing these results we proposed ECG patterns representative of different AFD stages characterized by increasing LV thickness. In patients with normal LV thickness (group A) we noticed a high prevalence of normal ECG (87%) and minor anomalies like LVH criteria/giant positive T waves (8%) and delta wave/slurred QRS onset together with borderline PR (8%). Differently patients with intermediate LV thickness (group B and C) show more heterogeneous ECG alterations: LVH/giant positive T waves (17% and 7%); LVH+LV strain (9% and 17%); incomplete RBBB associated with repolarization abnormalities (8% and 9%) which were more frequently associated with LVH criteria in group C than B (8% and 15% respectively). In patients with severe LVH (group D) we detected more significant anomalies, like complete RBBB associated to LVH and repolarization abnormalities (40%), sometimes with QRS fragmentation (13%). Conclusions ECG represents an important tool for early detection and long-term monitoring of cardiac involvement in AFD with particular ECG features that evolve together with the natural history of the disease and with the progression of the LVH. Their potential association with clinical events remains unknown.

Prognostic Implications of the Extent of Cardiac Damage in Patients With Fabry Disease

BackgroundThere is limited evidence on the risk stratification of cardiovascular outcomes in patients with Fabry disease (FD). ObjectivesThis study sought to classify FD patients into disease stages, based on the extent of the cardiac damage evaluated by echocardiography, and to assess their prognostic impact in a multicenter cohort. MethodsPatients with FD from 5 Italian referral centers were categorized into 4 stages: stage 0, no cardiac involvement; stage 1, left ventricular (LV) hypertrophy (LV maximal wall thickness >12 mm); stage 2, left atrium (LA) enlargement (LA volume index >34 mL/m2); stage 3, ventricular impairment (LV ejection fraction <50% or E/eʹ ≥15 or TAPSE <17 mm). The study endpoint was the composite of all-cause death, hospitalization for heart failure, new-onset atrial fibrillation, major bradyarrhythmias or tachyarrhythmias, and ischemic stroke. ResultsA total of 314 patients were included. Among them, 174 (56%) were classified as stage 0, 41 (13%) as stage 1, 57 (18%) as stage 2 and 42 (13%) as stage 3. A progressive increase in the composite event rate at 8 years was observed with worsening stages of cardiac damage (log-rank P < 0.001). On multivariable Cox regression analysis, the staging was independently associated with the risk of cardiovascular events (HR: 2.086 per 1-stage increase; 95% CI: 1.487-2.927; P < 0.001). Notably, cardiac staging demonstrated a stronger and additive prognostic value, as compared with the degree of LV hypertrophy. ConclusionsIn FD patients, a novel staging classification of cardiac damage, evaluated by echocardiography, is strongly associated with cardiovascular outcomes and may be helpful to refine risk stratification.

Left atrial remodeling in hypertrophic cardiomyopathy and Fabry disease: A CMR-based head-to-head comparison and outcome analysis

BackgroundHypertrophic cardiomyopathy (HCM) and Fabry disease cardiomyopathy (FD) are phenocopies, as they show left ventricular hypertrophy (LVH). The left atrium (LA) is emerging as a potential marker of disease severity in both cardiomyopathies. The present study compares HCM and FD cardiomyopathy with similar degree of LVH, exploring LA morpho-functional parameters and the correlates of clinical outcome. MethodsWe performed a comprehensive CMR-based comparison between 30 HCM and 30 FD patients matched on age, sex, BSA, LV mass and major cardiovascular risk factors affecting LA remodeling (arterial hypertension and diabetes). 30 healthy controls were also included. CMR feature tracking (CMR-FT) analysis, T1 mapping and conventional parameters were evaluated. Patients also underwent transthoracic echocardiography for LV diastolic function assessment. Clinical events at follow-up were collected (atrial and ventricular events, bradyarrhythmia, heart failure (HF) hospitalization and death). ResultsHCM patients showed greater LA remodeling compared to FD patients, namely higher LA end-systolic volume index (LAVi max), lower LA-ejection fraction (LA-EF) and worse reservoir (εs) and booster function (εa) (all p < 0.05). Accordingly, these parameters have demonstrated good potential for distinguishing between FD and HCM (AUC 0.68–0.73, all p < 0.05), with LAVi max being an independent predictor for HCM diagnosis (OR 1.07, 95%CI 1.011–1.132, p 0.02). Moreover, in HCM patients a significant association between εs and HF occurrence was observed at 2-year follow-up (OR 0.85, 95%CI 0.72–0.99, p 0.04). ConclusionsIn HCM, LA remodeling is greater than in FD cardiomyopathy with similar LVH, and reservoir strain is associated with HF at follow-up.

DISTRIBUTION OF THE DEGREE OF RIGHT VENTRICULAR HYPERTROPHY WITH DIFFERENT SEVERITY OF LEFT VENTRICULAR HYPERTROPHY IN ARTERIAL HYPERTENSION

Objective: To study the interrelation of the influence of left ventricular hypertrophy (LVH) on the frequency of the distribution of the degree of right ventricular hypertrophy (RVH) in patients who died suddenly during their lifetimes who suffered from arterial hypertension according to an autopsy Design and method: A retrospective study was conducted, which explored the autopsy protocols of patients suffered from hypertension (1999-2014) in Semey, Kazakhstan, suffered from hypertension during life and died suddenly. The normal wall thickness of the left ventricle was taken as 0.7-1.2 cm, the right ventricle 0.2-0.3 cm. The hypertrophy of the walls of the left and right ventricles was conventionally divided into 2 degrees. The hypertrophy of the walls of the left ventricle and the right ventricle was conditionally divided into 2 degrees, LVH: I degree - 1.3-2.0 cm, II degree - 2.1 or more; RVH: I degree - 0.4-0.6 cm, II degree - 0.7 cm or more. Results: When conducting a study of these protocols of persons, the thickness of the right ventricle was presented in 614 autopsy protocols. The distribution of LVH was the following: 1 degree 51.1%; 2 degree 48.9%. While the data on the distribution of RVH are as follows: the norm is 13%; 1st degree 33.9%; 2 degree 53.1%. At the same time, with 1 degree of left ventricular hypertrophy, the following distribution of RVH is noted: the norm is 22.6%; 1st degree - 46.8%; 2 degree - 30.6%. Then with 2 degrees of LVH, respectively: 3%, 20.3%, 76.7%, p &lt;0.0001. At 1 and 2 degrees of LVH, the frequency of detection of 2-degree RVH was, respectively, 30.6% and 76.8%. A direct correlation was found between the wall thickness of the left and right ventricles (r = 0.478). Conclusions: RVH is a common symptom in hypertension, up to 87% according to autopsy examination. LVH 1 and 2 degrees in the study group were equally distributed. The more pronounced the values of the degree of LVH, the more pronounced the degree of RVH. With LVH of the 2 degree, 2 times more often detected 2nd degree RVH.

The role of left ventricular hypertrophy measured by echocardiography in screening patients with ischaemia with non-obstructive coronary arteries: a cross-sectional study.

Many patients with ischaemia with non-obstructive coronary arteries (INOCA) have a poor prognosis. This study aims to explore the diagnostic value of left ventricular hypertrophy (LVH)-related ultrasound parameters in INOCA patients. The study group consisted of 258 patients with INOCA in this retrospective cross-sectional study, and these patients were free of obstructive coronary artery disease, previous revascularization, atrial fibrillation, ejection fraction < 50%, major distortions of left ventricular geometry, suspected non-ischaemic causes. Control individuals were matched 1:1 with study group according to age, sex, cardiovascular risk factors, and time of hospital stay. According to left ventricular mass index (LVMI) and relative wall thickness, left ventricular geometry was composed of concentric hypertrophy, eccentric hypertrophy, concentric remodeling and normal geometry. LVH-related parameters, left ventricular geometry, demographic characteristics, laboratory parameters and other echocardiographic indicators were compared between the two groups. Subgroup analysis was performed based on sex. LVMI in the study group was higher than that in the control group (86.86 ± 18.83g/m2 vs 82.25 ± 14.29g/m2, P = 0.008). The ratio of LVH was higher in the study group (20.16% vs 10.85%, P = 0.006). After subgroup analysis based on sex, LVMI differences (85.77 ± 18.30g/m2 vs 81.59 ± 14.64g/m2, P = 0.014) and the ratio of LVH differences (25.00% vs 14.77%, P = 0.027) still existed in females between the two groups. There was no difference in the constituent ratio of left ventricular geometry between the two groups (P = 0.157). Sex-based subgroup analysis showed no difference in the constituent ratio of left ventricular geometry between the two groups in females (P = 0.242). The degree of LVH in the study group was higher than that in the control group, suggesting that LVH may play an important role in the occurrence and development of INOCA. Moreover, LVH-related ultrasound parameters may be of higher diagnostic value for female INOCA patients than for male INOCA patients.

Microvascular Dysfunction Is Associated With Impaired Myocardial Work in Obstructive and Nonobstructive Hypertrophic Cardiomyopathy: A Multimodality Study

Background Two-dimensional speckle tracking echocardiography has been shown to correlate with microvascular dysfunction, a hallmark of hypertrophic cardiomyopathy (HCM). We hypothesized that there is an association between myocardial work and left ventricular ischemia, with incremental value to global longitudinal strain, in patients with HCM. Methods and Results We performed a prospective assessment of patients with HCM, undergoing 2-dimensional speckle tracking echocardiography and stress perfusion cardiac magnetic resonance. Results were stratified according to obstructive or nonobstructive HCM and the presence of significant replacement fibrosis (late gadolinium enhancement ≥15% of left ventricular mass). Seventy-five patients with HCM (63% men, age 55±15 years) were evaluated, 28% with obstructive HCM (mean gradient 89±60 mm Hg). Perfusion defects were found in 90.7%, involving 22.5±16.9% of left ventricular mass, and 38.7% had late gadolinium enhancement ≥15%. In a multivariable analysis, a lower global work index (r=-0.519, β-estimate -10.822; P=0.001), lower global work efficiency (r=-0.379, β-estimate -0.123; P=0.041), and impaired global constructive work (r=-0.532, β-estimate -13.788; P<0.001) significantly correlated with ischemia. A segmental analysis supported these findings, albeit with lower correlation coefficients. A global work index cutoff ≤1755 mm Hg% was associated with hypoperfusion with a sensitivity of 88% and a specificity of 71%, while the best cutoff for global longitudinal strain (>-15.5%) had a sensitivity of 64% and a specificity of 57%. The association between myocardial work and perfusion defects was significant independently of late gadolinium enhancement ≥15% and obstructive HCM. Conclusions Impaired myocardial work was significantly correlated with the extent of ischemia in cardiac magnetic resonance, independently of the degree of left ventricular hypertrophy or fibrosis, with a higher predictive power than global longitudinal strain.

Efekat metaboličkog sindroma na incidencu i stepen hipertrofije miokarda leve komore kod hipertenzivnih pacijenata

Metabolic syndrome (MetS) is characterized by the simultaneous presence of obesity, hypertension, dyslipidemia and hyperglycemia in an individual, which leads to an increased risk of cardiovascular disease (CVD). Left ventricular hypertrophy (LVH) is thickening of the heart muscle wall -hypertrophy of cardiomyocytes in concentric and/or elongation of cardiomyocytes and hyperplasia of connective tissue in eccentric hypertrophy with the participation of hemodynamic and non-hemodynamic factors (genetics, stress, other external factors). MetS, which essentially includesinsulin resistance, hyperinsulinemia, and hyperglycemia, alters myocardial metabolism and promotes myocardial inflammation, fibrosis, hypertrophy, and left ventricular remodeling. OBJECTIVE: To determine the impact of MetS, that is, obesity to the incidence and degree of severity of LVH in hypertensive patients with metabolic syndrome in comparison with the control group -hypertensive patients without metabolic syndrome. PATIENTS AND METHODS: Consecutive patients of the Office of Internal Medicine "Dr. Bastać" were examined, a total of 55 patients with hypertension, who were divided into two groups: the first group with MetS, 22 people, average age 56±8.5 years with BMI&gt;30kg /m 2 and waist circumference more than 80 cm for women and &gt;94 cm for men, the second control group without MetS-33 people, average age 52±14 years, with BMI&lt;30kg/m 2 . Echocardiography was done for all subjects on a Power Vision 6000 Toshiba echo camera with standard echocardiographic measurements in the M, B and Doppler technique, and the mass of the left ventricular myocardium was determined for them using the Devereux formula. RESULTS: The prevalence of LVH in group 1 with metabolic syndrome (MetS) was 64%, while in the control group without (MetS) it was 36%. There was a statistically significantly higher number of patients with LVH in hypertension with MetS compared to hypertensive patients of the control group without MetS (X2, p=0.027). In the group of hypertensive patients with MetS, the degree of severity of myocardial hypertrophy, that is, the myocardial mass , was statistically significantly higher compared to the control group (respectively 302±84g versus 224±89g, p=0.0002). Arterial pressure values were higher for both systolic and diastolic blood pressure 168/106 mmHg in hypertensive patients with MetS, but did not reach statistical significance in relation to blood pressure values in hypertensive patients without MetS (156/95 mmHg, p=0.16). CONCLUSION. Patients with metabolic syndrome and hypertension have a statistically significantly higher prevalence of left ventricular myocardial hypertrophy and a highly statistically significant degree of left ventricular hypertrophy compared to the control group of hypertensive individuals without MetS. Given that mean values of arterial pressure do not differ between groups, it can be concluded that non-hemodynamic factors for the development of LVH have an important role in the induction of a more severe degree of LVH in hypertensive patients with metabolic syndrome.

The association of dietary glutamine supplementation with the development of high salt-induced hypertension in rats.

Glutamine supplementation has been reported to affect blood pressure (BP). However, its role in the progression of hypertension induced by high salt diet (HSD) has not been elucidated. Male normotensive Wistar rats were exposed to high salt diet and treated with different doses of glutamine supplementation. Rats aged 6 weeks were assigned to five groups: (1) Normal-salt diet (0.3% NaCl, NSD); (2) High-salt diet (8% NaCl, HSD); (3) High-salt + low-dose diet (8% NaCl, 0.5 g of L-glutamine/kg body weight, HSLGD); (4) High-salt + middle-dose diet (8% NaCl, 1.5 g of L-glutamine/kg body weight, HSMGD); and (5) High-salt + high-dose diet (8% NaCl, 2.5 g of L-glutamine/kg body weight, HSHGD). After supplementing different doses of glutamine to male Wistar 6-week-old rats fed with HSD for 7 weeks, we found no difference in body weight among groups. Importantly, we showed that dietary L-glutamine supplementation could prevent the development of hypertension in a dose-dependent manner [dramatically lowering systolic blood pressure (SBP) and slightly reducing diastolic blood pressure (DBP) of hypertensive rats, while the differences of DBP between groups did not reach statistical significance]. Our data further elucidated that dietary glutamine supplementation mildly alleviated the degree of left ventricular hypertrophy, including interventricular septal thickness (IVST) and left ventricular posterior wall thickness (LVPWT) in hypertensive rats. Together, our results offer evidence that the dietary uptake of glutamine may be associated with attenuating the development of high salt-induced hypertension and slightly alleviating the degree of left ventricular hypertrophy in hypertensive rats. Therefore, glutamine supplementation may act as a prospective dietary intervention for the treatment of hypertension.

ECG as a storytelling of cardiac involvement evolution in Anderson Fabry disease

Abstract Background Cardiac involvement in Anderson-Fabry disease (AFD) is related to a progressive glycosphingolipid storage over time and is characterized by left ventricular hypertrophy (LVH), conduction abnormalities and myocardial fibrosis. ECG is useful for early recognition of AFD, however evidence is limited on the association between ECG alterations and disease stage. Purpose To assess the relationship between ECG characteristics and progressive cardiac involvement, from the pre-hypertrophic phase to phenotypes with increasing degree of LVH. Methods In a multicenter cohort, 183 AFD patients (40% male, age 47±12 years, 60% affected by “classical AFD”) underwent ECG and transthoracic echocardiography. Patients were divided into 4 groups according to the different degree of LV thickness measured in parasternal short axis view: group A ≤9 mm (N=46, 25%), group B 10–14 mm (N=77, 42%), group C 15–19 mm (N=45, 25%) and group D ≥20 mm (N=15, 8%). Patients with pacemaker and under 18 years of age were excluded. Results A normal ECG was present in 89% in group A, 59% in group B, 11% in group C and it was absent in group D. Short PR (&amp;lt;120 ms) was more frequent in group A, whereas with LVH increasing, median PR interval duration significantly prolonged among the 4 groups (136 [125–150]vs 141 [130–160] vs 160 [130–180] vs 170 [130–180] ms, p=0.002 respectively). Median P-wave duration was shorter in group A and B compared to group C and D (80 m vs 100 ms, p&amp;lt;0.001), while both QRS and QTc gradually increased. Median Sokolow-Lyon voltage criteria statistically augmented among the groups (22 [18–26] vs 27 [20–33] vs 32 [25–45] vs 35 [18–40] mm, p&amp;lt;0.001 respectively), along with right ventricular hypertrophy (0%, 1%, 11%, 8%, p=0.02). Right bundle branch block (RBBB) had a higher frequency in advanced stages (0%, 34%, 34%, 40%, p&amp;lt;0.001), with a prevalence of complete RBBB of 46% in group D. Similarly, left anterior fascicular block (0%, 7%, 18%, 46%, p&amp;lt;0.001) and QRS fragmentation (2%, 11%, 25%, 23%, p=0.009) were more common in advanced stages. No differences were found in left bundle branch block (LBBB), in low QRS voltages or in LV pre-excitation prevalence. According with the wall thickness increase, negative T waves were more frequent in lateral (4%, 21%, 70%, 77%, p&amp;lt;0.001) and inferior leads (6%, 15%, 32%, 46%, p 0.001), as well as their association with ST-T depression (4%, 17%, 64%, 46%, p&amp;lt;0.001). Giant negative T waves were present only in group C and D (16% and 31%) mainly representing a LVH distribution toward the apex. Conclusions ECG is a very useful tool to stage cardiac involvement evolution in AFD. Peculiar ECG characteristics evolve together with LV wall thickness: incomplete and progressively complete RBBB usually associated (preceding or following) LVH and/or typical repolarization abnormalities in inferior or lateral leads and giant negative T waves in the more advanced stages are the most frequent and typical ECG patterns. Funding Acknowledgement Type of funding sources: None.

Downregulation of Mannose-6-Phosphate Receptors in Fabry Disease Cardiomyopathy: A Potential Target for Enzyme Therapy Enhancement.

Background: The efficacy of enzyme replacement therapy (ERT) in mobilizing globotryaosylceramide (GB-3) from Fabry cardiomyocytes is limited. The mechanism involved is still obscure. Methods: Assessment of M6Pr, M6Pr-mRNA, and Ubiquitin has been obtained by Western blot analysis and real-time PCR of frozen endomyocardial biopsy samples, from 17 pts with FD, various degree of left ventricular hypertrophy, and maximal wall thickening (MWT) from 11.5 and 20 mm. The diagnosis and severity of FDCM followed definitions of GLA mutation, α-galactosidase A enzyme activity, cardiac magnetic resonance, and left ventricular endomyocardial biopsy with the quantification of myocyte hypertrophy and the extent of Gb-3 accumulation. All patients have received alpha or beta agalsidase for ≥3 years without a reduction in LV mass nor an increase in T1 mapping at CMR. Controls were surgical biopsies from 15 patients undergoing mitral valve replacement. Results: Protein analysis showed mean M6Pr in FDCM to be 5.4-fold lower than in a normal heart (4289 ± 6595 vs. 23,581 ± 4074, p = 0.0996) (p < 0.001): specifically, 9-fold lower in males, p = 0.009, (p < 0.001) and 3-fold lower in females, p = 0.5799, (p < 0.001) showing, at histology, a mosaic of normal and diseased cells. M6Pr-mRNA expression was normal, while ubiquitin showed an increase of 4.6 fold vs. controls (13,284 ± 1723 vs. 2870 ± 690, p = 0.001) suggesting that ubiquitin-dependent post-translational degradation is likely responsible for the reduction of M6Pr in FDCM. Conclusion: M6Pr expression is remarkably reduced in FDCM as a likely result of post-translational degradation. This may explain the reduced efficacy of ERT and be a therapeutic target for the enhancement of ERT activity.

Value of Electrocardiography to Distinguish Fabry Disease from Sarcomeric Hypertrophic Cardiomyopathy

Fabry disease (FD) is a rare genetic disorder that leads to left ventricular hypertrophy (LVH), frequently misdiagnosed as hypertrophic cardiomyopathy (HCM). We sought to assess the value of electrocardiography for distinguishing FD from HCM. We retrospectively reviewed and compared standard electrocardiograms and echocardiograms from 26 patients with FD and LVH and 33 sarcomeric patients with HCM, matched for gender, age, and degree of LVH. The mean age of patients with FD was 46years (interquartile range) (28 to 53) and of HCM 50 (30 to 61) years (p=0.27). Of them, 16 (61%) and 25 (76%) were male, respectively (p=0.26). Indexed left ventricular mass was 166g/m² in FD versus 181g/m² in HCM (p=0.88). All patients with FD and 30 (91%) with HCM were in sinus rhythm (p=0.25). A higher prevalence of right bundle branch block (RBBB) was observed in FD (27%) versus HCM (6%) (p=0.03). The PR interval was shorter in FD, 140ms (120-160) versus 160ms (140 to 180) (p=0.004). P-wave duration was longer in patients with FD, 100ms (80 to 120) versus 80ms (80 to 100) (p=0.01). The PQ interval (PR interval minus P-wave duration) was shorter in patients with FD, 40ms (20 to 45) versus 80ms (40 to 80) (p=0.001). There were no differences regarding P-wave amplitude, QRS complex duration, corrected QT length, conduction or repolarization abnormalities, Sokolow-Lyon index, and Cornell index. After multivariate adjustments for RBBB, PR interval, P-wave duration, and PQ interval, a PQ interval ≤40ms and RBBB were significantly associated with FD. In conclusion, there are electrocardiogram characteristics, such as the presence of RBBB or a PQ interval ≤40ms, that may be helpful for screening and reducing the delay in FD diagnosis.

ECHOCARDIOGRAPHY PARAMETERS IN PATIENTS WITH STAGE 2 ARTERIAL HYPERTENSION COMPLICATED BY CHRONIC KIDNEY DISEASE

Abstract. The purpose of the research is to explore patient’s echocardiography parameters with stage 2 arterial hypertension complicated by chronic kidney disease (CKD). Material and methods: the study involved 100 patients with stage 2 essential hypertension (46 men and 54 women with average age of 59.09±13.51 years). The first group included patients with arterial hypertension complicated by CKD (50 people). The control group consisted of patients with hypertension, in whom the course of hypertension was not complicated by CKD (50 people) - the 2nd group. In the first two days of hospitalization, blood pressure was measured, blood creatinine was assessed, GFR was calculated, the presence of microalbuminuria was assessed, the threshold of taste sensitivity to table salt (TSTSS) was determined, and a transthoracic echocardiographic study (Echo-CG) was performed. The data are presented in the form of M±SD with a normal distribution of the trait, Me±IQR with a description of the trait different from the normal distribution and a percentage ratio (%). To assess the statistical relationship between the indicators, Spearman's rank correlation coefficient (r) was calculated. Results. The study showed that in patients with hypertension complicated by CKD, there are higher blood pressure numbers, almost half of them have insufficient antihypertensive therapy. They have higher values of indicators characterizing the degree of LV hypertrophy and lower values of ejection fraction than in patients without CKD. A direct correlation was found between PS consumption and echocardiographic parameters characterizing LV size and its hypertrophy in AH patients with CKD. At the same time, these indicators were significantly higher in patients with high PHCPS compared to those with a low threshold. Conclusion. The data obtained from the results of ECHO-CG allow us to expand our understanding of the pathogenesis of AH, taking into account such complications as CKD, and can be used for timely correction of antihypertensive therapy, which will prevent the process of progression of AH staging, before the appearance of systemic complications of CKD, and, therefore, improve the prognosis of the disease.

When is Significant Left Ventricular Hypertrophy Acceptable for Donor Heart Selection

<h3>Purpose</h3> Extended criteria of donors for heart transplant (HTx) include many factors, such as left ventricular hypertrophy (LVH), decreased LVEF, older donor age, inotrope dependence, as well as gender and size mismatch. It has also been reported that various combinations of extended criteria risk factors appear to have worse outcomes depending on severity of the extended criteria characteristic. We sought to assess if severity of LVH with acceptable donor age and ischemic time is associated with increased mortality. <h3>Methods</h3> Between 2010 and 2020, we assessed 156 donor hearts with varying degrees of LVH defined as left ventricular septal thickness greater than 1.2 cm. Donor hearts were then divided into those that had IVS between 1.2 to <1.3 cm, 1.3 to <1.5 cm, ≥1.5 cm. In addition, an assessment was made for the same LVH groups versus donor age categorized as donor age ≥50 years old and donor ischemic time >240minutes. <h3>Results</h3> Severity of LVH with donor age <50 years and ischemic time <240 min appear to have acceptable 1-year survival. However, older donor age/long ischemic time with LVH are higher risk for 1-year mortality. (see table) <h3>Conclusion</h3> Severe LVH (IVS >1.5 cm) in donor hearts appears to be acceptable with donor age <50 years and ischemic time <240 minutes.