Left Ventricular Hypertrophy Research Articles

Refractory Chylothorax and Ventricular Hypertrophy Treated with Trametinib in a Patient with Noonan Syndrome: 18-Month Follow-Up

RASopathies are a group of genetic syndromes caused by germline mutations in genes involved in the RAS/Mitogen-Activated Protein Kinase signaling pathway, which regulates cellular proliferation, differentiation, and angiogenesis. Despite their involvement at different levels of this pathway, RASopathies share overlapping clinical phenotypes. Noonan syndrome is the most prevalent RASopathy, with an estimated incidence of 1 in 2500 live births, and it is typically inherited in an autosomal dominant manner, with 50% of cases involving gain-of-function mutations in the PTPN11 gene. De novo mutations are common, accounting for 60% of cases. The phenotype of Noonan syndrome includes characteristic facial and physical features, congenital cardiac defects, lymphatic and cerebrovascular anomalies, renal malformations, hematological abnormalities, developmental issues, and an increased risk of cancer. Severe congenital cardiac defects and lymphatic abnormalities significantly impact prognosis, contributing to increased morbidity and mortality. Recent therapeutic advancements have introduced trametinib, an MEK1/2 inhibitor, for treating Noonan syndrome patients with severe cardiac and lymphatic complications. To assess its efficacy, here, we present a case of a newborn with Noonan syndrome who exhibited refractory chylothorax, ventricular hypertrophy, and pulmonary stenosis who was treated with trametinib. The patient demonstrated significant improvement in chylothorax and left ventricular hypertrophy, though pulmonary stenosis persisted. This case further confirms trametinib’s potential as a therapeutic option for severe Noonan syndrome complications, emphasizing the need for further clinical trials to optimize treatment protocols and evaluate long-term outcomes.

A phenomap of TTR amyloidosis to aid diagnostic screening.

Cardiac amyloidosis due to transthyretin (ATTR) remains an underdiagnosed cause of cardiomyopathy. As awareness of the disease grows and referrals for ATTR increase, clinicians are likely to encounter more atypical forms of the condition in clinical practice. Therefore, physicians and treating cardiologists should be aware of the full phenotypic spectrum of ATTR. The phenotypic manifestation of ATTR varies depending on the stage of the disease, the presence and type of TTR mutation and the patient's comorbidities. ATTR findings can be grouped into four major categories: clinical profile and cardiac phenotype, extra-cardiac findings, electrocardiogram and imaging findings, which cumulatively form the full phenomap of ATTR. Results from any diagnostic test for ATTR should be interpreted in light of the pre-test probability for the disease. Findings that suggest negative markers for ATTR can point towards other forms of amyloidosis (such as AL amyloidosis) or alternate causes of left ventricular hypertrophy, including hypertrophic cardiomyopathy or Fabry disease. The rising number of referrals for ATTR cardiomyopathy presents a challenge in daily clinical practice. To prevent an increase in false-positive diagnostic test results, an ATTR phenomap can serve as a valuable tool for guiding diagnostic assessments, interpreting test outcomes and prioritizing appropriate referrals for ATTR screening.

Left atrial function in uraemic patients: Four-dimensional automatic left atrial quantitative technology study.

This study aimed to evaluate the utility of left atrial volume and function in uraemic patients using four-dimensional automatic left atrial quantification (4D auto LAQ) technology. Thirty-four undialysed uraemic patients (U-ND group), 60 dialysed uraemic patients (U-D group), and 32 healthy volunteers (N group) were enrolled in our current study. Conventional echocardiographic parameters were recorded, and left atrial volume and strain parameters were analysed to determine statistical differences among the three groups. The Pearson correlation coefficient was employed to assess the relationships between left atrial ejection fraction and left atrial strain parameters. Compared to the N group, uraemic patients often displayed left atrial enlargement and left ventricular hypertrophy. Significant increases were noted in left atrial diameter, interventricular septum thickness, left ventricular posterior wall thickness, E/e', diastolic blood pressure, systolic blood pressure, left atrial minimum volume, left atrial maximum volume, left atrial pre-atrial contraction volume, left atrial emptying volume and left atrial maximum volume index (P<0.05). Conversely, the e', E/A ratio and left atrial reservoir longitudinal strain were significantly decreased (P<0.05). However, no statistically significant differences were observed in the aforementioned parameters between the U-ND and U-D groups. The absolute values of left atrial conduit longitudinal strain and left atrial conduit circumferential strain, as well as left atrial passive ejection fraction, were notably lower in the U-D group compared to the N and U-ND groups, with statistically significant differences identified among the three groups (P<0.05). Uraemic patients exhibit marked left atrial enlargement and left ventricular hypertrophy, coupled with altered atrial function, particularly ductal dysfunction in the U-D group. The 4D auto LAQ technology proves advantageous in detecting these alterations, offering a promising tool for thorough cardiac assessment in this patient cohort.

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.

Diagnostic and prognostic value of ECG-predicted hypertension mediated left ventricular hypertrophy using machine learning

Abstract Background Hypertension is the commonest cause of left ventricular hypertrophy (LVH). Using cardiac magnetic resonance (CMR) imaging, four distinct hypertension mediated LVH phenotypes have been reported: normal LV, LV remodelling, eccentric LVH and concentric LVH. Early detection of hypertensives with LVH can enable timely initiation of therapy however a CMR based screening strategy is costly, particularly in low resource settings. The electrocardiogram (ECG) is an inexpensive screening tool and can detect LVH but its capacity to discriminate between the 4 phenotypes is unknown. Purpose To classify hypertension mediated LVH phenotypes from the ECG using machine learning (ML) and test for associations of ECG predicted LVH phenotypes with incident cardiovascular outcomes. Methods ECG markers with a known physiological association with LVH (including QRS markers, Sokolow-Lyon, and Cornell) were extracted from the 12-lead ECG of 20,439 hypertensive participants in UK Biobank. Three classification models, logistic regression, support vector machine (SVM) and random forest, were trained in 80% of the participants using extracted ECG markers and clinical variables. The remaining 20% individuals were included in the test set for performance measurement. External validation was sought in 877 hypertensives from the Study of Health in Pomerania (SHIP). Subsequently, we tested for associations between the four ECG-predicted LVH phenotypes and incident major adverse cardiovascular events (MACE) and heart failure using Cox proportional hazard regression in the UK Biobank test set with median follow-up of 4.2 years. Results Among UK Biobank participants (mean age ± standard deviation 65 ± 7.4 years), 23,190 had normal LV, 894 LV remodelling, 218 eccentric and 103 concentric LVH. Classification performance of the three models was comparable, but SVM showed consistent results (accuracy 0.79, sensitivity 0.59, specificity 0.87, AUC 0.69) and superior prediction of eccentric LVH (AUC 0.86). In SHIP (55 ± 12.7 years), 704 had normal LV, 134 LV remodelling, 12 eccentric and 24 concentric LVH. In the external validation performed in SHIP, SVM had accuracy of 0.75 (sensitivity 0.51, specificity 0.85, AUC 0.65), with superior prediction of eccentric LVH (AUC 0.76), as shown in Figure 1. Ventricular rate and QRS amplitude (P&amp;lt;0.001) were the features most strongly associated with LVH. In the test set of UK Biobank, setting normal LV as the reference group, the ECG predicted eccentric LVH group was associated with heart failure (Hazard Ratio 3.42, confidence interval 1.06-9.86), there were no associations with MACE (Figure 2). Conclusions ECG-based ML classifiers were able to discriminate the four hypertension mediated LVH phenotypes with external validation demonstrating robustness. This automated approach enhances capabilities of non-specialists and potentially represents an accessible screening strategy for the early detection of hypertensives with LVH.

Left atrial strain differences between hypertensive and sarcomeric left ventricular hypertrophy: a sign of sarcomeric auricular myopathy?

Abstract Introduction In clinical practice, left ventricular (LV) hypertrophy is a common finding that can be caused by physiologic or pathologic conditions. An etiologic diagnosis is extremely important because it may change the prognosis and management of the patient and his family. Left atrial (LA) dysfunction is common due to diastolic dysfunction but, in patients with sarcomeric LV hypertrophy, primary cardiomyopathy disease could also be present. Purpose To evaluate if there are differences in LA function between arterial hypertension (HT) and hypertrophic cardiomyopathy (HCM) patients. Methods 73 patients with HCM (according to ESC guidelines criteria) and 82 patients with HT (under treatment with ≥1 hypertensive drug for ≥3 months) and ≥13mm of LV hypertrophy underwent an echocardiography to assess LA function with strain analysis and LV diastolic function. Continuous normally distributed variables were compared with T-student test and categoric variables with square-chi or exact Fisher test if required, accepting as significant a p-value &amp;lt;0.05. Results Globally, HCM patients showed thicker LV walls and larger LA indexed volumes (18.7±4.7 vs. 13.3±0,8 mm and 44.9±20.7 vs. 30.7±8.8 ml/m2, p&amp;lt;0.000 for both). Also, HCM patients presented diastolic dysfunction and atrial fibrillation history in a higher frequency (31 vs. 7.6% and 16.4% vs. 0%, p&amp;lt;0.000 for both). LA strain was significantly lower in HCM patients as compared to the HT group (LA contractile 11.5±5.8 vs. 17.2±4.4, p&amp;lt;0.000; LA conduit 12.2±5.4 vs. 13.3±3.8, p=0.041; and LA reservoir 23.9±8.7 vs. 31.1±5.9, p&amp;lt;0.000). In the subgroup of patients with moderate-severe LV hypertrophy (&amp;lt;17mm) and no significant mitral regurgitation (n=103; HCM=21, HT=82), LA contractile strain remained lower in HCM as compared to HT patients (13.2±4.8% vs. 17.2±4.4%, p&amp;lt;0.000) (figure 1); without differences in diastolic dysfunction, LA volumes, significant mitral regurgitation or atrial fibrillation history. Conclusions Our results show that LA strain is more impaired in HCM patients as compared to HT patients. Specifically, contractile LA strain remained lower even in those patients with moderate-severe LV hypertrophy, despite having similar LV diastolic function, LA indexed volumes, significant mitral regurgitation, or atrial fibrillation history. These findings could be caused by HCM involvement of the LA myocytes. In the context of moderate-severe hypertrophy of unknown origin with non-significant mitral regurgitation, the detection of abnormally reduced LA strain could indicate the presence of an HCM.Figure 1

Clinical significance of echocardiographic left ventricular hypertrophy for predicting left atrial appendage thrombotic milieu in patients with atrial fibrillation and CHA2DS2-VASc scores of 0-2

Abstract Background Even in patients with atrial fibrillation (AF) and low CHA2DS2-VASc scores, it is not always possible to completely rule out left atrial appendage (LAA) thrombus. Further stratification of the risk of LAA thrombosis in these patients remains an important yet unresolved issue. Left ventricular hypertrophy (LVH) is a prognostic risk factor in AF and has been associated with a worse prognosis, particularly in those with low CHA2DS2-VASc scores. Purpose To investigate the clinical significance of echocardiographic LVH for risk stratifying LAA thrombogenic milieu as a surrogate for cardioembolic risk in patients with AF and CHA2DS2-VASc scores of 0–2. Methods This was a single-center, retrospective study. We enrolled 707 consecutive patients with AF and CHA2DS2-VASc scores of 0–2 who underwent transesophageal echocardiography. The patients were divided into two groups based on the presence or absence of LVH. Owing to the racial differences in normative left ventricular mass index (LVMI) reference values, LVH was defined in this study using Japanese reference values. LVH was defined as LVMI ≥108 g/m2 for men and ≥98 g/m2 for women. LAA thrombogenic milieu was defined by any of the following findings: (1) thrombus, (2) severe spontaneous echo contrast or sludge, or (3) average LAA flow velocity ≤20 cm/s. Alongside conventional parameters, longitudinal strain values for the left ventricle (LV) and left atrium (LA) were obtained using transthoracic echocardiography. Results The mean age was 61 ± 10 years, and 12.2% were female. Overall, 77 (10.9%) patients were classified into the LVH group, and 41 (5.8%) of patients had LAA thrombogenic milieu. The LVH group exhibited a significantly higher prevalence of LAA thrombogenic milieu than the non-LVH (32.5% vs. 2.5%, p&amp;lt;0.001). Figure 1 illustrates the details of the patients with the LAA thrombogenic milieu based on LVH presence and CHA2DS2-VASc scores. The LVH group included six patients with LAA thrombus, even with CHA2DS2-VASc scores of 2, whereas the non-LVH group had no patient with LAA thrombus. Table shows the association of LAA thrombogenic milieu and clinical and echocardiographic parameters by logistic regression analysis; LVH independently associated with LAA thrombogenic milieu after adjusting for clinical factors (including CHA2DS2-VASc score, AF type, and serum brain natriuretic peptide levels) and conventional echocardiographic parameters (including LV ejection fraction, LV end-diastolic volume index, and LA volume index). Moreover, LVH provided incremental prognostic value for predicting LAA thrombogenic milieu, even when added to the longitudinal strain of the LV and LA reservoir strains (p&amp;lt;0.001). These findings are summarized in Figure 2. Conclusion Echocardiographic LVH significantly improves the prediction of LAA thrombogenic milieu, offering potential utility in further cardioembolic risk stratification for patients with AF and CHA2DS2-VASc scores of 0–2.

Left ventricular hypertrophy, wall thickness, and histological myocyte alteration in end-stage heart failure: a call for a standard definition

Abstract Objective This study aimed to examine the relationship between different left ventricular hypertrophy (LVH) classification criteria according to the American Society of Echocardiography (ASE), and anatomical measurement of LV wall thickness (LVWT) and histological evidence of myocyte hypertrophy. Methods Data from 146 consecutive patients (47 years; 75% were male) who have undergone heart transplantation were analysed. Fixed ventricles were dissected and measured in weight after both atria, great vessels, and epicardial fat were removed. The fixed biventricular weight was calculated as 87% of total weight (the effect of fixed formalin reduced the total weight by 3%). Anatomical LVWT was measured with a ruler at LV free wall where maximal thickness is located. A comprehensive echocardiogram was performed in all patients before heart transplantation. LVM and relative wall thickness (RWT) (2 PWT/LVEDD) were measured by M-mode echocardiography in parasternal long-axis view. Patients were considered to have LVH when the LVM index exceeds 95 g/m2 in women and exceeds 115 g/m2 in men. Patients were considered to have concentric LVH when RWT &amp;gt; 0.42. LVWT was measured using 2D echocardiography perpendicular to the LV long axis. Results Of 146 explanted hearts, dilated cardiomyopathy (CM), cardiac amyloid, and hypertrophic CM were diagnosed in 53 (47%), 1 (1%), and 8 (5%) patients, respectively. Anatomic ventricular mass correlated with echocardiographic LVM (r=0.5, p &amp;lt; 0.01). Anatomic LVWT modestly correlated with echocardiographic LVWT (r=0.2, p=0.01). Of 146 patients, echocardiographic normal LV geometry, concentric LV remodelling, concentric LVH, and eccentric LVH were present in 22 (15%), 6 (4%), 14 (10%), and 104 (71%), respectively. Increased LVWT (≥ 13 mm) assessed by 2-D echocardiography was present in normal LV geometry (5%), concentric LV remodelling (5%), concentric LVH (57%), and eccentric LVH (33%) (p &amp;lt;0.001) in those classified by ASE guidelines. Anatomic LVWT (≥ 13 mm) was present in normal LV geometry (14%), concentric LV remodelling 5%), concentric LVH (14%), and eccentric LVH (80%) (p &amp;lt;0.001) in those classified by ASE guidelines. Histological myocyte hypertrophy was present in normal LV geometry (12%), concentric LV remodelling (2%), concentric LVH (11%), and eccentric LVH (70%) (p &amp;lt;0.001) in those classified by ASE guidelines. Conclusions 2D-derived echocardiographic increased LVWT in patients with LVH defined by increased LVM index was present in approximately 30-50%. Furthermore, anatomical increased LVWT in those with LVH classified by ASE guidelines was present in a varying range of 10-70%. Patients with concentric LVH had a low prevalence of histological myocyte hypertrophy (approximately 10%). Inconsistencies in classification methods reveal the need for more robust LVH terminologies and definition that is consistent across cardiac imaging and anatomico-pathological examination, particularly in patients with CM.

Impact of changes in left heart geometry on predicting new-onset atrial fibrillation in patients with hypertension

Abstract Background Hypertension-induced left ventricular hypertrophy (LVH) increases end-diastolic LV pressure and contributes to left atrial enlargement (LAE), which are associated with development of atrial fibrillation (AF). However, the impact of LVH and LAE and their regression following antihypertensive therapy on AF incidence remains unclear. Purpose This study aimed to investigate the impact of changes in the LVH and LAE status on the occurrence of new-onset AF (NOAF). Methods This retrospective analysis included patients with sinus rhythm who underwent echocardiography at hypertension diagnosis and after 6–18 months. LVH was defined as LV mass index &amp;gt;115 g/m2 (men) and &amp;gt;95 g/m2 (women), and LAE was defined as LA volume index &amp;gt;42 ml/m2. LVH and LAE regression was defined as the absence of LVH and LAE on follow-up echocardiography, respectively. The occurrence of NOAF was assessed in relation to changes in LVH and LAE status. Results Among the 1,464 patients included in the study, 163 (11.1%) patients developed NOAF during a median follow-up of 63.8 months (interquartile range, 35.9–128.5 months). On average, 12 electrocardiograms per patient were reviewed for AF detection. New-onset LVH (adjusted HR 1.88, 95% CI 1.20–2.94, P=0.006) and LAE (adjusted HR 1.89, 95% CI 1.05–3.40, P=0.034) were significant predictors of NOAF. Conversely, regression of LVH (adjusted HR 0.51, 95% CI 0.280.91, P=0.022) or LAE (adjusted HR: 0.30, 95% CI 0.15–0.63, P=0.001) after antihypertensive therapy was associated with a reduced risk of NOAF. The risk of NOAF was higher in patients with LVH and LAE together (adjusted HR 4.30, 95% CI 2.81–6.56, P&amp;lt;0.001) than in those with either LVH or LAE, or those with neither, as determined by follow-up echocardiography. Conclusion In patients with hypertension and sinus rhythm, regression of LVH and LAE following antihypertensive therapy is associated with a decreased incidence of NOAF, whereas newly developed LVH or LAE is associated with a higher risk of NOAF. The changes in left heart geometry can serve as a predictive marker for NOAF in patients with hypertension.

Aortic valve replacement and mortality with left ventricular hypertrophy in setting of normal LVEF

Abstract Background Without symptoms, indications for aortic valve replacement (AVR) in severe aortic stenosis (AS) differ for individuals with normal vs. low/decreasing left ventricular ejection fraction (LVEF). Conceptually, the development of left ventricular hypertrophy (LVH) could also indicate ventricular injury and potential benefit with earlier AVR. However, little is known about the comparative effectiveness of AVR in individuals with LVH. As such, unlike low or dropping LVEF, development of LVH is not in itself an indication for AVR in clinical guidelines. Methods Initially, 1,232,492 echocardiography reports from 12 hospitals were identified from 1 January 2000 to 22 November 2022, and previously validated natural language processing modules were then applied to identify aortic gradients, LVEF, and presence of LVH. These reports were linked to mortality data, key comorbidities with a 2-year lookback covariate window, and date of any AVR. We then isolated echocardiograms demonstrating normal flow severe AS, LVEF ≥ 55% and LVH. Chart reviews were conducted to reduce missing data and outcomes were censored on the date of the chart review (October 4, 2023). To assess the association between AVR and mortality, Cox proportional hazards models considering treatment status (ie, AVR or not) were used with the index echocardiogram as time zero. Covariates used in risk-adjustment were chosen a priori based on conditions and laboratory values used in cardiac surgery mortality risk-adjustment, since those variables could plausibly confound the treatment decision. To address immortal time bias, AVR was considered a time-varying covariate. Multiple additional approaches with propensity scores were performed as sensitivity analyses. Results After application of inclusion and exclusion criteria, 4856 unique patients remained for analysis. Of those, 2043 (42.1%) received AVR with 841/2043 (41.2%) receiving surgical AVR and 1202/2043 (58.8%) receiving transcatheter AVR. Patients who received AVR had lower unadjusted mortality than those who did not receive AVR (33.6% vs. 47.1%, p &amp;lt; 0.001). After adjustment, and accounting for time-dependence of AVR, AVR was associated with reduced mortality (HR 0.81, 95% CI 0.73-0.89, p &amp;lt; 0.0001). The sensitivity analyses were all consistent with the primary analysis. Conclusions AVR was associated with reduced mortality for patients with severe AS, preserved LVEF, and LVH. This association persisted even after accounting for time-dependence, which tends to reduce the observed effectiveness of procedures in observational data. With over a million echocardiograms over more than 20 years, this is the largest known analysis of AVR outcomes in individuals with severe AS and LVH. Our findings suggest LVH may be a high-risk phenotype of individuals with AS, similar to dropping LVEF. As such, these results raise the potential of more proactive AVR clinical guidelines in individuals with LVH, even when LVEF is normal.Survival in AVR Vs No AVR

Prevalence and prognostic implication of left ventricular hypertrophy defined by different echocardiographic criteria

Abstract Objective Echocardiographic criteria of left ventricular hypertrophy (LVH) recommended in the international guidelines are derived from Caucasian population, which could be less accurate in estimating the LVH burden in other ethnic groups. LVH is a well-known prognostic factor and assessing the LVH burden based on ethnic-specific criteria have important implications. To evaluate the prevalence and prognostic implications of LVH in general Chinese population according to the criteria of the Echocardiographic Measurements in Normal Chinese Adults (EMINCA) study and the international guidelines. Methods Nationally representative populations aged ≥ 35 years (n=20210, mean age 56.0 years, women 53.3%) were enrolled from the China Hypertension Survey. LVH criteria of the EMINCA study was left ventricular mass index (LVMI) &amp;gt; 109 g/m2 for men and &amp;gt; 105 g/m2 for women; and the international guidelines was LVMI &amp;gt; 115 g/m2 for men and &amp;gt; 95 g/m2 for women. Results The prevalence of LVH defined by the EMINCA study and international guidelines was 8.3% (≈ 56.8 million) and 11.7% (≈ 80.1 million) respectively. LVH defined by the EMINCA study was associated with adjusted hazard ratio (HR) of 1.58 (95% CI 1.18-2.12; P-value=0.002) for cardiovascular death and 1.21 (95% CI 0.98-1.49; P-value=0.07) for all-cause death; while defined by the international guidelines, LVH was associated with adjusted HR of 1.33 (95% CI 0.98-1.80; P-value=0.07) for CV death and 1.22 (95% CI 1.00-1.50; P-value=0.054) for all-cause death. Conclusions Prevalence and prognostic implications of LVH in general Chinese population differ by different echocardiographic criteria, supporting the application of ethnic-specific criteria.Cumulative rate of outcomes at follow-upLVH and CV death and all-cause death

Incidence and risk factors for development of left ventricular hypertrophy in Fabry disease

Abstract Background Left ventricular hypertrophy (LVH) is the principal cardiac manifestation of Fabry disease (FD). This study aimed to determine the incidence and predictors of LVH development in a contemporary cohort of patients with FD and no LVH at baseline evaluation. Methods Consecutively referred adult (age ≥16 years) patients with FD were enrolled into an observational cohort study. Patients were prospectively followed in a specialist cardiomyopathy centre and the primary endpoint was the first detection of LVH (left ventricular mass index (LVMi) ≥115 g/m2 in men and ≥95 g/m2 in women). Results From a cohort of 393 patients, 214 (age 35.8 ±13.8 years; 61 [29%] males) had no LVH at first evaluation. During a median follow-up of 9.4 years (interquartile range [IQR] 4.7-12.7), 55 patients (24.6%) developed LVH. The estimated incidence of LVH was 11.3% (95% confidence interval [CI] 6.5-16.1) at 5 years, 29.1% (95%CI 21.5-36.7) at 10 years, and 45.0% (95%CI 33.8-62.4) at 15 years of follow-up. On multivariable analysis, independent predictors for LVH development were age (hazard ratio [HR] 1.04 [95%CI 1.02-1.06] per 1 year increase, p-value &amp;lt;0.001), male sex (HR 2.90 [95%CI 1.66-5.09], p-value &amp;lt;0.001), and an abnormal ECG (HR 3.10 [95%CI 1.72-5.57], p-value &amp;lt;0.001). The annual rate of change in LVMi was +2.77 (IQR 1.45-4.62) g/m2/year in males and +1.38 (IQR 0.09-2.85) g/m2/year in females (p-value &amp;lt;0.001). Conclusions Approximately one quarter of FD patients developed LVH during follow-up. Age, male sex, and ECG abnormalities were associated with a higher risk of developing LVH in patients with FD.Central Illustration

Cardiac magnetic resonance (CMR) height-based allometric scaling in Southeast Asians; implications in the diagnosis and prognosis of left ventricular hypertrophy (LVH): the REMODEL study

Abstract Background Left ventricular hypertrophy (LVH) is a strong predictor of adverse cardiovascular outcomes (1). Although normalizing LV mass (LVM) to height exponents has been shown to reduce variability from body size, specific recommendations for height exponents are lacking due to the scarcity of normal cohorts to define appropriate height exponents (2). Cardiac magnetic resonance (CMR) is increasingly used in assessing LVM, and the existing body of research is based primarily on the MESA cohort (3). While the MESA cohort is ethnically diverse, the intrinsic effects of ethnicity may not fully be discerned if certain ethnic groups are under-represented. Purpose We aimed to demonstrate the diagnostic and prognostic implications of establishing height exponents specific to sex in a Southeast Asian cohort. Methods Non-overweight/obese Southeast Asian healthy volunteers (n=416) were used to establish appropriate height exponents and normal reference ranges of LVM. The impact of these height exponents was examined in a separate cohort of Southeast Asians with hypertension (n=878). All individuals underwent standardized cardiovascular magnetic resonance imaging (CMR). Primary outcome was a composite of acute coronary syndrome, heart failure hospitalization, stroke, and cardiovascular mortality. Cox regression analysis of various LVH measures were adjusted for 24-hour systolic blood pressure, diabetes, and hyperlipidemia. Results The height exponents for healthy females and males were 1.57 and 2.33, respectively. In patients with hypertension, sex-specific height exponents significantly increased the detection of LVH compared with body surface area (BSA) indexing (47% [n=409/878] versus 27% [n= 236/878], p&amp;lt;0.001). Most individuals re-classified to LVH with sex-specific height exponents were overweight (33.1%, n=58/175) or obese (64.6%, n=113/175). There were 37 primary events over 60 [37-73] months of follow-up. Regardless of indexing method, LVH was independently associated with increased adverse events (sex-specific height exponent hazard ratio (HR): 2.8 [1.25-6.29], P=0.013). The prediction ability of LVH diagnosis by sex-specific height exponents was similar to BSA indexing (HR: 5.43 [2.49-11.8], P&amp;lt;0.001). Conclusions Reference ranges specific to the ethnicity, sex and imaging modality are necessary to establish appropriate height exponents. Although utilizing sex-specific height exponents to index LVM resulted in significantly more LVH reclassification when compared with BSA indexing, this did not translate to a notable improvement in event prediction. Further research into alternative methods of LVM indexing is warranted.Abstract SummaryPredictive Ability of LVH Measures

Application of the 2016 ase-eacvi criteria for the assessment of diastolic function in arterial hypertension

Abstract Background No data are available on diagnostic algorithms recommended by guidelines for the assessment of diastolic dysfunction (DD) in patients with arterial hypertension. Purpose To fill this gap, we evaluated left ventricular (LV) diastolic function in hypertensive patients matched with healthy subjects. Methods Healthy subjects, hypertensive patients without and with LV hypertrophy (LVH) were matched 1:1:1 based on age, sex, and body mass index from two prospective registries. All participants had normal LV ejection fraction (EF). Diastolic function was assessed basing on 2016 ASE-EACVI guidelines, by applying algorithm A, recommended in normal LVEF, and algorithm B recommended in reduced LVEF or normal LVEF and myocardial disease. Results A total of 717 participants were enrolled. By applying algorithm A, an indeterminate pattern was found in 0.4% of healthy subjects, in 6.3% of hypertensive patients without LVH (p=0.015 vs. healthy subjects), and in 21% of hypertensive patients with LVH (p=0.001 vs. healthy subjects). DD was absent in healthy individuals, whereas it was found in 2% and 8% of hypertensives without (p=0.06) and with LVH (p=0.001 vs. healthy subjects), respectively. By applying algorithm B, no cases of indeterminate diastolic function were found. DD was observed in 2.9% of healthy subjects, 7% and 10.5% of hypertensives without (p=0.001 vs. healthy subjects) and with LVH (p=0.002 vs. healthy subjects). Conclusion When diastolic function is assessed by echocardiography, the use of algorithm A should be limited only to truly normal subjects, whereas algorithm B should be applied to all patients with hypertension irrespective of LVH

Coexistence of coronary microvascular dysfunction and left ventricular hypertrophy can predict prognosis of patients with nonobstructive coronary arteries

Abstract Background Previous studies have reported that coronary microvascular dysfunction (CMD) and left ventricular hypertrophy (LVH) were associated with adverse cardiovascular events. The aim of this study was to determine the prognostic impact of coexistence of abnormal coronary flow reserve (CFR) and left ventricular mass index (LVMI). Methods and results This study included 297 patients who underwent intracoronary physiological assessment including CFR for suspected myocardial ischemia without significant stenosis in the epicardial coronary artery at our hospital from December 2019 to March 2023. Of 297 patients (female: n=89 [30%], age: 70±11 years), 93 (31%) had CMD (CFR&amp;lt;2.5) and 133 (45%) had LVH (LVMI&amp;gt;95 g/m2 for female and &amp;gt;115 g/m2 for male). We excluded patients with history of heart failure (HF). Patients were classified into 4 groups based on the cut-off values of CFR and LVMI: group 1 (no CMD nor LVH, n=109); group 2 (only LVH, n=95); group 3 (only CMD, n=55) and group 4 (both CMD and LVH, n=38). Patients of group 4 had a larger proportion of female (female 19%, 34%, 24% and 61% in group 1 to 4 respectively). There was no significant difference in left ventricular ejection fraction between patients of each groups. Clinical follow-up was performed for major adverse cardiovascular events (MACE) including cardiovascular death, myocardial infarction and hospitalization for new-onset HF. During a median follow-up of 753 days, the cumulative MACE-free survival rate at 2 year were 99.0%, 98.9%, 95.6% and 90.0% in groups 1 to 4. Group 4 showed significantly higher risk of MACE at 2 year compared with group 1 (hazard ratio [HR] 2.6; 95% confidence interval [CI] 1.3-5.3; p=0.009). Notably, Group 4 showed the highest incidence of hospitalization for new-onset HF than any other groups. Conclusion Patients with both CMD and LVH showed significantly higher risk for MACE and new onset of HF. The combined classification based on CFR and LVMI would identify the high-risk patients for MACE as well as new-onset HF.

Proteomic biomarkers and pathway analysis for progression to heart failure in three epidemiological representative cohorts.

Biomarkers associated with asymptomatic ventricular dysfunction might improve risk stratification and identify pathways leading to heart failure (HF). We explored the association between proteomic biomarkers and left ventricular hypertrophy (LVH), diastolic dysfunction (DD) and incident HF in three population-based cohorts. A chip was used to measure 92 protein biomarkers in blood samples from >1500 Malmö Preventive Project (MPP) participants, of whom 514 had LVH (34%), 462 had DD (32.4%) and, over a median follow-up of 13 (11-14) years, 130 developed HF (7.7%). Findings were confirmed in the STANISLAS (n > 1500, 238 participants with LVH, 76 with DD) and HOMAGE case-control (562 cases of incident HF, 871 controls) cohorts. In multivariable logistic or Cox regression analyses adjusted for age, sex and cardiovascular risk factors, N-terminal pro-B-type natriuretic peptide (NT-proBNP) was associated with LVH, DD and incident HF in all cohorts: MPP (LVH odds ratio [OR] [95% confidence interval] 1.48 [1.28-1.71]; DD OR 1.71 [1.53-1.92]; HF HR 1.98 [1.66-2.36]); STANISLAS (LVH OR 1.20 [1.02-1.41]; DD OR 1.46 [1.12-1.90]); HOMAGE (HF HR 1.85 [1.62-2.12]). Galectin-4, growth differentiation factor 15 and suppression of tumorigenicity-2 were associated with incident HF in MPP and HOMAGE. A pathway enrichment analysis suggested that inflammation and viral infection were related to incident HF. In conclusion, our study reinforces the role of NT-proBNP as a key biomarker for asymptomatic cardiac dysfunction and incident HF, consistent with its established use in clinical practice. This underscores the value of NT-proBNP for identifying patients at high risk for HF, and provides insights into pathways leading to HF and potential therapeutic targets.

Electrocardiographic criteria for the diagnosis of left ventricular hypertrophy in patients with severe aortic stenosis

Abstract Introduction There is a lack of data regarding the performance of current electrocardiographic (EKG) criteria for left ventricular hypertrophy (LVH) in patients with severe aortic stenosis (AS). Purpose To test the performance of the current EKG scores to diagnosis LVH in AS patients, and also to compare the performance of a new proposed score. Methods The present study evaluated 80 patients with severe AS that underwent cardiac magnetic resonance to diagnose LVH, defined as left ventricular indexed mass of 95 g/m² for female and 115 g/m² for male patients. The EKG criteria used for left ventricular hypertrophy were Sokolow-Lyon criteria, Romhilt-Estes point score system, Cornell voltage criteria and Peguero-Lo Presti criteria. Results Among the 80 patients included in analysis, 58.7% were male and the mean age was 64±8 years. There was a high prevalence of comorbidities, highlighting diabetes (32.5%), hypertension (67.5%), atrial fibrillation (5.0%) and coronary artery disease (11.3%). Regarding echocardiogram, the median left ventricle ejection fraction was 64 (56-68)% and the median indexed aortic valve area was 0.43 (0.35-0.49) cm²/m². Cardiac magnetic resonance analysis demonstrated a mean left ventricle mass of 168±55g, and the LVH incidence was 26.3%. Regarding EKG, Strain pattern was found in 49.1% of the patients, Cornell voltage criteria was positive in 51.3%, Sokolow-Lyon criteria in 51.3%, Romhilt-Estes point score system in 42.5% and Peguero-Lo Presti criteria in 61.3%. Discriminative capacity of electrocardiographic criteria for LVH is shown in Figure 1. Peguero-Lo Presti score had the best diagnostic accuracy in the overall population and in male sex (AUC 0.776), while Cornell voltage criteria had the best diagnostic accuracy in female patients (AUC 0.776). Based on linear regression model, the proposed score was created to predict LVH at cardiac magnetic resonance: 48 + (1.3 x Deepest S wave) + (0.5 x S wave in V1 or V2 plus R wave in V5). The proposed score cutoff value of 90.5 mm had a sensitivity of 0.765 and specificity of 0.707 (for male sex: 0.769 and 0.655, respectively; for female sex: 0.750 and 0.759, respectively). Compared to the scores described in the literature, the proposed score had the best area AUC for the overall population (Figure 1), for female and male patients (AUC 0.796, 0.819 and 0.780, respectively). Conclusion In patients with severe AS, the proposed score had the best diagnostic accuracy compared to the scores described in the literature for LVH identification, followed by Peguero-Lo Presti score, even when analyzed based on gender. Besides, the proposed score had also acceptable sensitivity and specificity for LVH detection.AUC of electrocardiographic scores.

Cardioprotective efficacy of combined therapy with azilsartan, indapamide, and nitrendipine in patients with essential hypertension

Abstract Objective To conduct a comparative assessment of the six-month cardioprotective efficacy of combined therapy using azilsartan with indapamide and nitrendipine in patients with essential hypertension (EH). Materials and Methods The study included 101 male and female patients with grade I–II arterial hypertension (AH) according to the classification (ESC/ESH, 2018), who were undergoing outpatient treatment at the Republican Specialized Scientific-Practical Medical Center of Cardiology. The mean age of the patients was 53.1±11.2 years, and the mean duration of AH was 8.5±7.2 years. Initially and after 6 months of therapy, echocardiography was performed to determine the left ventricular myocardial mass index (LVMMI) and left ventricular (LV) echo geometry types. Echocardiography (ECHO) was performed using the "En VisorC" ultrasound system (Philips, Netherlands). Statistical significance was considered for all analyses with p &amp;lt;0.05. Results All patients were divided into 2 groups: Group 1 - patients on combined antihypertensive therapy (AHT) with azilsartan and indapamide (n=50) and Group 2 - patients on therapy with azilsartan and nitrendipine (n=51). The mean daily dose of azilsartan was 49.3±6.0 mg, nitrendipine was 10.88±4.3 mg, and indapamide was 1.69±0.5 mg. In Group 1, the LVMMI initially was 127.4±32.9 g/m2, and after treatment, it was 110.3±29.0 g/m2 (p&amp;lt;0.001); in Group 2, it was 138.7±31.9 g/m2 and 116.6±30.3 g/m2, respectively (p&amp;lt;0.001). The degree of LVMMI reduction in Group 1 was -13.3±15.6% compared to Group 2, which was -14.4±17.9% (p&amp;gt;0.05). During therapy with azilsartan, indapamide, and nitrendipine, the reduction of LVMMI in EH patients was associated with a decrease in the concentric type of left ventricular hypertrophy (LVH) in both therapy groups: in both groups, a significant increase in the LV diastolic filling pattern index/LVMMI was observed, which was 0.51±0.07 ml/g before treatment and 0.57±0.14 ml/g after treatment in Group 1 (p&amp;lt;0.001), and 0.50±0.11 ml/g before treatment and 0.54±0.12 ml/g after treatment in Group 2 (p&amp;lt;0.02). Significant regression of LVH with 6-month combined therapy in both groups was accompanied by an improvement in LV echo geometry. Initially, there were 12 patients (11.9%) with unchanged LV echo geometry, concentric remodeling was detected in 9 patients (8.91%), eccentric LVH in 30 patients (29.7%), and concentric LVH in 50 patients (49.5%). In the dynamics, the number of patients with normal LV echo geometry increased to 41 patients (40.6%), with concentric LVH decreased to 34 patients (33.6%), with concentric remodeling decreased to 7 patients (7%), and with eccentric LVH decreased to 19 patients (18.8%) (χ2=21.635, p&amp;lt;0.001). Conclusion Achieving target blood pressure levels provided high cardioprotective efficacy of combined therapy with azilsartan, indapamide, and nitrendipine with improvement in LV echo geometry in both groups.

Antihypertensive treatment of masked hypertension guided by ambulatory blood pressure monitoring: a double-blind, placebo-controlled trial

Abstract Background Masked hypertension, office normotension combined with out-of-office hypertension, is associated with target organ damage (TOD), but whether antihypertensive treatment guided by out-of-office blood pressure (BP) would reduce TOD is unproven. Purpose To assess TOD change on antihypertensive treatment guided by ambulatory BP monitoring. Methods We conducted a double-blind, placebo-controlled randomized trial at 15 Chinese hospitals. Enrolment started on February 14, 2017 and follow-up ended on October 31, 2021. Patients of either sex, aged 30-70 years, not on antihypertensive drugs were eligible, if at two screening visits 1-week apart office BP was &amp;lt;140/&amp;lt;90 mm Hg and the 24 hour, daytime or nighttime ambulatory BP was ≥130/≥80, ≥135/≥85, or ≥120/≥70 mm Hg, respectively. Patients had ≥1 sign of TOD: ECG left ventricular hypertrophy (LVH), brachial-ankle pulse wave velocity (baPWV) ≥1400 cm/s, or urinary albumin-to-creatinine ratio (ACR) ≥3.5 mg/mmol in women and ≥2.5 mg/mmol in men. Active antihypertensive treatment consisted of allisartan starting at 80 mg/day to be increased to 160 mg/day at month 2 and to be combined with amlodipine 2.5 mg/day at month 4, if the ambulatory BP remained uncontrolled. Matching placebos were used likewise in the control group. The primary endpoint included normalization of baPWV, ACR or LVH or ≥20% reduction in baPWV or ACR. Results Of 320 patients (43.1% women; mean age 54 years), 153 were randomized to active antihypertensive treatment and 167 to placebo. At baseline, office BP averaged 130/81 mm Hg and the 24 hour BP 136/84 mm Hg. The prevalence of elevated baPWV, ACR and LVH was 97.5%, 12.5%, and 7.8%. The 24-hour systolic/diastolic decreased by 9.0/5.6 mm Hg (95% CI: 7.5-10.5/4.8-6.5 mm Hg) on active treatment and by 1.4/1.0 mm Hg (-0.1-2.8/0.2-1.8 mm Hg) on placebo. Regression of TOD, the primary outcome, occurred more frequently in patients randomized to active treatment than in those assigned to placebo with 1 year rate of 45.8% (95% CI: 37.9-53.7%) and 25.8% (19.1-32.4%), respectively (P&amp;lt;.001 for between-group differences in BP and TOD). Per-protocol and subgroup analyses were confirmatory. Conclusions Masked hypertensive patients require antihypertensive treatment guided by out-of-office BP monitoring before subclinical TOD progresses to major cardiovascular complications.

Sex-related differences in left ventricular geometry patterns in patients with arterial hypertension

Abstract Background Sex-specific differences in left ventricular (LV) geometry is key for tailoring management strategies for arterial hypertension. Purpose To evaluate sex-related differences in LV geometry patterns at baseline and their evolution over time in hypertension. Methods From a prospective registry, we included hypertensive patients with at least 1 year follow-up, without prevalent cardiovascular disease or incident myocardial infarction, with normal LV ejection fraction and no chronic kidney disease of stage III or more. Four LV geometry patterns were assessed: normal geometry, concentric remodeling, eccentric and concentric LV hypertrophy (LVH). Results A total of 6427 patients (age 53±11 years, 43% females) were included. At baseline, a normal geometric pattern was less common in female than in male patients (50% vs. 72%, p&amp;lt;0.001). LVH was more prevalent among female than male patients (47% vs. 23%, p&amp;lt;0.001), with a higher prevalence of eccentric LVH (40% vs. 18%, p&amp;lt;0.001). Female sex was independently associated with LV remodeling (odds ratio, 2.36, 95% confidence intervals, 2.12-2.62, p&amp;lt;0.001). At long-term follow-up (mean 6.1 years, IQR 2.8-8.6 years), the proportion of patients with LV remodeling increased in both sexes, although a normal LV geometry remained less frequent in female than male patients (43% vs. 67%, p&amp;lt;0.001), with differences persisting in eccentric (41% vs. 21%, p&amp;lt;0.001) and concentric LVH (11% vs. 5%, p&amp;lt;0.001). Conclusions We found relevant sex-related differences in LV geometry among patients with hypertension. Females have a higher risk of LV remodeling at baseline compared with men, with differences persisting at long-term follow-up.