Interventricular Septal Thickness Research Articles

Plasma metabolomic analysis reveals the therapeutic effects of Jiashen tablets on heart failure.

Heart failure is a chronic progressive condition that significantly affects the quality of life of patients with high hospitalization and mortality rates. Jiashen tablets (JST), a Chinese herbal formula, have been reported to be an effective treatment against heart failure, however the underlying mechanisms remain obscure. This study was designed to determine the effect of JST on the treatment of heart failure and delineate the underlying mechanisms by an untargeted metabolomics approach. The chronic heart failure model was established by the permanent ligation of the left anterior descending coronary artery in rats. The cardiac functions of rats, including left ventricular ejection fraction (LVEF) and fractional shortening (LVFS), left ventricular internal diameter end diastole (LVIDd) and end systole (LVIDs), and interventricular septum thickness in diastole (IVSd) and in systole (IVSs), were measured by echocardiography. Biochemical analysis and histopathological examination were also performed to evaluate therapeutic effects of JST for treating heart failure. UHPLC-QTOF-MS/MS coupled with multivariate statistical analyses were applied for plasma metabolic profiling to identify biomarkers and potential mechanisms of JST in the treatment of heart failure. Jiashen tablets could improve the cardiac function of heart failure rats and thus ameliorate heart failure via enhancing rat LVEF and LVFS and decreasing LVIDd, LVIDs, IVSd, and IVSs. Results of biochemical analysis and histopathological examination revealed that JST could reduce the serum lactate dehydrogenase (LDH) activity and the level of NT-pro BNP, markers of heart failure and myocardial damage, and inhibit myocardial fibrosis. Furthermore, in metabolomics analysis, a total of 210 metabolites with significant differences were identified between heart failure rats and normal rats, among which 29 metabolites were significantly restored after JST treatment. These metabolites were primarily involved in tryptophan metabolism, branched-chain amino acid metabolism, fatty acids β-oxidation, and glycerophospholipid metabolism. The present study illustrated the therapeutic effect of JST for the treatment of heart failure and delineated the underlying mechanisms mainly relating to the regulation of amino acid metabolism and lipid metabolism in heart failure rats.

Features of hemodynamic and structural parameters of the heart in young people with varying stages of cardiometabolic risk

Background. Cardiometabolic diseases are one of the leading causes of disability and mortality worldwide, which justifies the relevance of studying their early manifestations.
 Aim. To analyze the hemodynamic and structural echocardiographic parameters of the heart in relation to cardiometabolic risk factors and its staging according to the Cardiometabolic Disease Staging (CMDS) scale in young patients.
 Material and methods. 109 patients were examined: 57 males (52.3%) and 52 females (47.7%) aged with a median of 36.1 [32.639.2] years without cardiometabolic diseases. The design of the study was a cross-sectional case-control study. The parameters of cardiometabolic risk were assessed with its calculation and assessment taking into account the stage according to the CMDS scale. Echocardiography was performed in M- and B-modes. The data were processed using the SPSS Statistics 23 program. The MannWhitney U test, the KruskalWallis test, and the Pearson and Fisher 2 tests were used. Correlation analysis according to Spearman was carried out.
 Results. The first stage of cardiometabolic risk was established in 17 examined patients (15.6%), the rest had stage 2 (n=57; 52.3%) or stage 3 (n=35; 32.1%) of cardiometabolic risk. Deviations from the normal values of hemodynamic echocardiographic parameters were not revealed. The frequency of increase in the index of relative thickness, the thickness of the posterior wall of the left ventricle, the interventricular septum thickness, the myocardium mass of the left ventricle did not differ (p=0.1980.983). A direct correlation between the left atrial, end-systolic and diastolic volumes, left ventricle wall thickness, and an inverse relationship between the left ventricular ejection fraction and cardiometabolic risk factors was established. At the 3rd stage of cardiometabolic risk, higher values of the left atrial volume (47 [4649] ml; p=0.005), end-systolic (30.42 [29.2332.04] ml; p=0.001) and diastolic (79 [7881] ml; p=0.003) volumes of the left ventricle and lower left ventricular ejection fraction (61 [60.3562.65] ml; p=0.004) than on the 1st and 2nd stages were diagnosed.
 Conclusion. An increase in the cardiometabolic risk is associated with an increase in preload and afterload on the left heart.

Time-dependent change of relative apical longitudinal strain index in patients with wild-type transthyretin amyloid cardiomyopathy.

This study was conducted to investigate the meaning of left ventricular (LV) apical sparing in patients with wild-type transthyretin amyloid cardiomyopathy (ATTRwt-CM). 165 patients who were diagnosed with ATTRwt-CM at Kumamoto University Hospital from January 2002 to December 2020 and had sufficient data for two-dimensional speckle tracking echocardiography were enrolled. Of these, 86 patients (52%) had LV apical sparing (relative apical longitudinal strain index (RapLSI)>1.0). Multivariable logistic regression analysis revealed the following variables were significantly associated with LV apical sparing: interventricular septal thickness in diastole (odds ratio (OR), 1.19; 95% confidence interval (CI), 1.01-1.41; p<0.05); E/e' ratio (OR, 1.06; 95% CI, 1.00-1.11; p<0.05); and heart-to-contralateral ratio by 99mTc-labeled pyrophosphate scintigraphy (OR, 3.40; 95% CI, 1.07-10.83; p<0.05).Next, we compared RapLSI at the time of diagnosis with that during the follow-up period (396days (346-458) after diagnosis) in 92 patients. RapLSI increased significantly during the follow-up period compared with RapLSI at diagnosis in the non-LV apical sparing group (0.89±0.32 vs 0.74±0.18, p<0.01) but not in the LV apical sparing group (1.33±0.53 vs 1.39±0.45, p=0.46). A total of 12 patients (29%) in the non-LV apical sparing group developed LV apical sparing and 11 patients (22%) in LV apical sparing group diminished LV apical sparing during the follow-up period. Approximately half of ATTRwt-CM patients did not have LV apical sparing at diagnosis. Because RapLSI in ATTRwt-CM significantly changed over time, repeated two-dimensional speckle tracking analysis is important for suspected ATTR-CM patients.

Interventricular Septum Thickness for the Prediction of Coronary Heart Disease and Myocardial Infarction in Hypertension Population: A Prospective Study.

The aim of the present study was to evaluate the prognostic value of interventricular septum thickness (IVSd) on the incidence of cardiovascular diseases. Based on the general population in Northeast China, 10,349 participants were successfully followed up for echocardiography over a median follow-up time of 4.66 years, among which 4801 were hypertensive. Coronary heart disease (CHD) and myocardial infarction (MI) incidence were followed up. Cox proportional hazards models were used to estimate the association of the baseline IVSd with adverse outcomes. IVS hypertrophy increased incident rates of CHD and MI compared with normal IVSd in the overall population and in the female sex-stratification group. In males, IVS hypertrophy had parallel increase rates of CHD (all p &lt; 0.05). Kaplan-Meier analysis showed that IVS hypertrophy could predict CHD and MI incidence and CHD-free and MI-free survival. Multivariable Cox analysis revealed that IVS hypertrophy was correlated with CHD incidence (HR = 1.155, 95% CI = 1.155-2.861, p = 0.01) and MI incidence (HR = 2.410, 95% CI = 1.303-4.458, p = 0.005). In women, IVS hypertrophy was independently associated with CHD and MI incidence (all p &lt; 0.05). Our prospective cohort study illustrated that IVS hypertrophy detected by echocardiography has a prognostic significance for CHD and MI. Therefore, the early detection of IVSd should be conducted to avoid adverse outcomes in further clinical practice.

High Prevalence of Cardiac Amyloidosis in Clinically Significant Aortic Stenosis: A Meta-Analysis.

There is growing evidence of coexistence of aortic stenosis (AS) and transthyretin cardiac amyloidosis (CA). Not screening AS patients at the time of hospital/clinic visit for CA represents a lost opportunity. We surveyed studies that reported the prevalence of CA among AS patients. Studies that compared patients with aortic stenosis with cardiac amyloidosis (AS-CA) and AS alone were further analyzed, and meta-regression was performed. We identified nine studies with 1,321 patients of AS, of which 131 patients had concomitant CA, with a prevalence of 11%. When compared to AS-alone, the patients with AS-CA were older, more likely to be males, had higher prevalence of carpal tunnel syndrome, right bundle branch block. On echocardiogram, patients with AS-CA had thicker interventricular septum, higher left ventricular mass index (LVMI), lower myocardial contraction fraction, and lower stroke volume index. Classical low-flow low-gradient (LFLG) physiology was more common among patients with AS-CA. Patients with AS-CA had higher all-cause mortality than patients with AS alone (33% vs. 22%, P = 0.02) in a follow-up period of at least 1 year. CA has a high prevalence in patients with AS and is associated with worse clinical, imaging, and biochemical parameters than patients with AS alone.

The Effect of Growth Hormone Therapy on Cardiac Outcomes in Noonan Syndrome: Long Term Follow-up Results

Cardiac involvement is common in Noonan syndrome (NS). Concerns have been raised regarding the effect of recombinant growth hormone (rGH) use on ventricular wall thickness and a possible increased risk of cardiac side effects. This study aimed to investigate the effect of rGH on the development of hypertrophic cardiomyopathy and other cardiac findings in NS. Patients under the age of 18 years and diagnosed with NS according to the Van der Burgt criteria, were included. Patients were divided into two groups according to those receiving rGH or not at the time of obtaining cardiac measurements. Before and after the treatment, electrocardiographic and echocardiographic (ECHO) assessments were made, including interventricular septal thickness, left ventricular internal diameter, and left ventricular posterior thickness. Results were expressed as Z scores. Twenty-four NS subjects (16 boys, eight girls) were included. At the beginning of the follow up, the overall height standard deviation score was -2.56±0.94. Sixteen were on rGH. The mean rGH treatment duration was 8.3±3.8 years, and the mean dose was 0.22±0.04 mg/kg/week. The final height was 169±8.2 cm, and 10 of 11 patients who reached the final height received rGH. There was no difference between the rGH and non-rGH groups in terms of ECHO parameters pre-and post-treatment. In this cohort, there was no change in ECHO parameters on rGH and during follow-up. These results suggest that rGH is safe in NS patients with cardiac pathology under close follow-up.

Hypertrophic Obstructive Cardiomyopathy Repair with Coronary Artery Bypass Surgery: A Case Report

Background: Hypertrophic obstructive cardiomyopathy (HOCM) is a cardiac condition of an abnormal interventricular septum (IVS) thickening. It is due to an autosomal dominant mutation in sarcomeric protein genes. It had many phenotypes with different distribution of myocardial hypertrophy. Septal myectomy remains the treatment of choice for hypertrophic obstructive cardiomyopathy resistant to medical therapy. However, controversy exist regarding standard treatment option(s). Description of the Case: Here we described a case of 47-year-old patient admitted with diagnosis of acute coronary syndrome, with typical chest pain of angina class II, shortness of breath class-II (NYHA), smoker on regular renal hemodialysis. Echocardiography showed HOCM, IVS thickening, normal Left ventricle global systolic function and mild to moderate eccentric regurge. Coronary angiography revealed normal left main with total (LAD) proximal occlusion, proximal and mid (LCX) (50%) occlusion, first (OM) mid (90%) lesion, (RCA) dominant with non-flow limiting lesions. He was submitted to open heart surgery with four grafts, sub-valvular myomectomy, and successful myomectomy. Distal anastomosis was done first then myomectomy then proximal anastomosis. Patient extubated after (9) hours with stable hemodynamics and complete neurological condition, with accepted drains output. He gradually weaned from inotropic support and chest drains removed on 3rd postoperative day. All lines and pacemakers were removed, the wound was dry with stable sternum and improvement of all symptoms. Then discharged home after 9 days of hospital stay on medical treatment. Postoperative echocardiography showed significant improvement. Conclusion: Surgical treatment is the standard option in treatment of HOCM to improve symptoms.

Midterm results of latent outflow tract obstruction in hypertrophic cardiomyopathy after septal myectomy: A propensity score-matched study.

The midterm clinical outcomes of patients with latent left ventricular outflow tract (LVOT) obstruction who undergo septal myectomy are unclear. Therefore, this study aimed to evaluate the clinical outcomes of patients with latent LVOT obstruction who underwent septal myectomy. We studied 34 patients with hypertrophic cardiomyopathy (HCM) and latent LVOT obstruction who underwent septal myectomy in 2011-2019 at Anzhen Hospital. After 2:1 propensity score matching, the study cohort included 34 patients with latent LVOT obstruction and 68 patients with resting LVOT obstruction. Compared to patients with resting LVOT obstruction, patients with latent LVOT obstruction had a thinner interventricular septal thickness (18.2 ± 3.2 mm vs. 20.4 ± 5.6 mm; p = .01), while the proportion of moderate or severe mitral regurgitation was significantly higher (26.5% vs. 5.9%; p = .003). Moreover, the proportion of mitral valve procedures (26.5% vs. 5.9%; p = .004) was significantly higher in patients with latent LVOT obstruction. However, there was no intergroup difference in cardiovascular death (5.9% vs. 1.5%, p = .26). Furthermore, the 5-year survival rates after sudden cardiac death (100.0% vs. 91.7%; p = .26) and cardiovascular death (95.5% vs. 89.0%; p = .32) were similar between HCM patients with latent versus resting LVOT obstruction. Midterm clinical outcomes were similar and excellent in a matched cohort of HCM patients with latent versus resting LVOT obstruction after septal myectomy.

Echocardiographic Changes in Cardiac Function After Thoracic Endovascular Aortic Repair: A Systematic Review and Meta-Analysis

Evidence suggests thoracic stent grafts increase the aortic stiffness postimplantation. Our objective was to examine the effect of thoracic aortic stenting on heart function, as demonstrated with echocardiography. We considered nonrandomized studies examining echocardiographic parameters (left ventricle ejection fraction (LVEF), left ventricle end-diastolic (LVED) and end-systolic diameter (LVESD), posterior wall thickness (LVPWT), interventricular septal thickness (IVST), mass, and mass index) pre and poststent graft implantation in patients with thoracic aortic diseases (aneurysm, dissection, and blunt injury). MEDLINE and CENTRAL were searched (up to March 2021) for eligible studies. The National Institutes of Health Quality Assessment Tool was used for risk of bias assessment. Echocardiographic data pre and postimplantation were compared using the pooled standardized mean difference (SMD) and 95% confidence interval (CI). Four studies were included in the meta-analysis. Three of the studies were judged to be "good" quality and one "fair". Nonsignificant differences pre and postimplantation were found for ejection fraction (SMD=-0.53, 95% CI=-1.8 to 0.728, P=0.406), IVST (SMD=-0.79, 95%, CI=-3.25 to 1.66, P=0.52), EDD (SMD=-0.10, 95% CI=-0.48 to 0.28, P=0.60), ESD (SMD=-0.66, 95% CI=-2.35 to 1.02, P=0.44), and PWT (SMD=-2.20, 95% CI=-5.89 to 1.47, P=0.24). A trend toward an increase in mass postimplantation was found (SMD=0.28, 95%, CI=-0.03 to 0.60, P=0.08), but there was no significant difference in mass index (SMD=0, 95%, CI=-0.195 to 0.195, P=1). Thoracic aortic stenting does not appear to significantly impact cardiac physiology as indicated by echocardiographic parameters.

One stone hits two birds: transcatheter mitral valve edge-to-edge repair for hypertrophic obstructive cardiomyopathy and severe mitral regurgitation.

A 68-year-old woman presented with dyspnoea on exertion and intermittent palpitation followed by near fainting. The transthoracic echocardiography (TTE) revealed asymmetric myocardial hypertrophy with an interventricular septal wall thickness of 15.2 mm at diastole, and elongated anterior leaflet (Panel B) with systolic anterior motion (SAM; Panels A and C, right). Left ventricular outflow tract (LVOT) obstruction with a peak flow velocity (Vp) of 5.18 m/s and a peak pressure gradient (PPG) of 107 mmHg (Panel D) and severe eccentric mitral regurgitation (MR) were observed (Panel E). The transoesophageal echocardiography (TEE) showed MR mostly originated from A2 and A3 (Panel F). The patient was finally diagnosed as hypertrophic cardiomyopathy (HCM). After the Heart Team discussion and share decision-making, the patient then received transcatheter mitral valve edge-to-edge repair (TEER) with MitraClip system and a single XTR clip. The intraoperative TEE displayed residual trace MR (Panel J and TTE Panel I), abolishment of SAM phenomenon (Panel G, right), and an LVOT Vp of 1.84 m/s and PPG of 13 mmHg (Panel H). After the procedure, the left ventricular global longitudinal strain and circumferential strain also increased (pre-operation Panel C, left; post-operation Panel G, left). The patient got rid of prior symptoms immediately after the procedure, and she was then safely discharged home within a week.

Myocardial remodeling and fibroblast growth factor in patients with resistant hypertension

Aim. To study the prevalence and severity of left ventricular hypertrophy (LVH), its relationship with fibroblast growth factor (FGF23) in patients with resistant hypertension (RH) depending on the effectiveness of multiagent antihypertensive therapy.Material and methods. The study included 92 patients diagnosed with RH. All patients underwent 24-hour ambulatory blood pressure monitoring (ABPM), echocardiography, general laboratory tests, and the serum FGF23 level was determined.Results. According to ABPM results, patients were divided into following groups: 1st — controlled RH (n=44) and 2nd — uncontrolled (n=48) RH. The groups were comparable in sex, age, main clinical and anthropometric parameters. In group 2, the main parameters of ABPM were higher. There were no differences in general laboratory tests, In the group of uncontrolled RH, the level of FGF23 was higher — 11,7 [8,5; 15,4] pmol/ml vs 9,2 [7,1; 11,6] pmol/ml in the 1st group (p=0,0036). According to echocardiography, a comparable violation of left ventricular (LV) diastolic function, an increase in left atrial size, LV mass (LVM) and LVM index were found. In patients of the 2nd group, large values of interventricular septal thickness were revealed — 1,3 [1,2; 1,4] cm vs 1,2 [1,1; 1,3] cm in the 1st group (p=0, 0043) and relative LV wall thickness (LVWT) — 0,50 [0,48; 0,53] vs, 0,45 [0,43; 0,50] in the 1st group (p&lt;0,0001). In the 1st and 2nd groups, concentric LVH was more common (18 (41%) patients in the 1st and 26 (54,1%) in the 2nd (p=0,044) groups) than eccentric LVH (15 (34,1%) and 13 (27,1%) patients in the 1st and 2nd groups, respectively). Correlation analysis revealed a positive relationship between pulse pressure and HTN duration (r=48, p=0,02) and FGF23 level (r=0,62, p=0,004). The LVM index was positively associated with the diastolic pressure-time index (BP) (r=51, p=0,02). A positive correlation was found between relative LVWT and pulse pressure (r=0,64, p=0,02) and a negative relationship with the duration of regular antihypertensive therapy (r=47, p=0,04), A strong relationship was found between LVEF and FGF23 levels (r=0,75, p=0,005).Conclusion. For patients with uncontrolled resistant hypertension, an increase in pulse pressure and myocardial remodeling in the form of concentric hypertrophy are more characteristic. FGF23 is significantly higher in uncontrolled RH and is positively associated with pulse pressure and relative LVWT.

Evaluation for the Relationship Between Normal Serum Level of Thyroid Hormones and Left Ventricular Systolic and Diastolic Dysfunction

Background: Thyroid hormones play an important role in cardiac tissue function. Therefore, it is important to understand the relationship between thyroid hormone levels and cardiac disorders. Objectives: The present study aimed to assess the relationship between normal serum level of thyroid hormones and left ventricular systolic and diastolic dysfunction. Methods: In this cross sectional descriptive retrospective study, 391 patients were selected. They were referred to the Rajaie Cardiovascular Research Center, Tehran, Iran from 2019 to 2021. After extracting echocardiographic and laboratory data from the clinical records, the parameters affecting the left ventricular systolic and diastolic dysfunction were analyzed using statistical software. Results: The mean age of patients was 41 ± 12.8 years. Among them 58.1% of all patients were female. Tricuspid regurgitation (TR) severity had a significant relationship with thyroid stimulating hormone (TSH) level (P = 0.02). End diastolic interventricular septum thickness (IVSD) was inversely associated with thyroxin4 (T4) level (P = 0.04). Mitral valve inflow deceleration time (MVDT) was inversely correlated with thyroxin3 (T3) (P = 0.04). Left ventricular ejection fraction (LVEF) was inversely related to TSH level and end diastolic right ventricular internal diameter (RVIDd) was directly related to TSH (P = 0.05). Conclusions: Thyroid hormone levels in the normal range can be associated with the tricuspid regurgitation severity, end diastolic right ventricular internal diameter (RVIDd), mitral valve inflow deceleration time (MVDT), and. end diastolic interventricular septum thickness (IVSD). Due to the high prevalence of heart disorders, information on thyroid hormone levels can be helpful in the identification and timely treatment of these disorders.

Influence of Dorper lamb development from birth to 120 days of age on clinical and echocardiographic parameters

The expansion of the sheep model in research represents an attractive and economically beneficial academic reason for investigations in sheep echocardiography. The present study aimed to evaluate the clinical and echocardiographic parameters in Dorper lambs during the developmental period. Emphasis was placed on the use of the species in translational research for the echocardiographic diagnosis of congenital heart diseases, which can contribute to improvements in interventionist techniques. Ten Dorper lambs were evaluated at the following time points: 24 h after birth and 7, 14, 21, 30, 60, 90 and 120 days of age. Clinical parameters were compiled, and echocardiogram records were obtained without sedation. Rectal temperature was lower on the first day compared to the others. From 21 days of life, there was a reduction in HR, with differences between time points. Mean and systolic blood pressure differed, with the highest values at 90 and 120 days of age. The thickness of the interventricular septum in diastole (IVSd) increased as age progressed, with the highest value at 120 days of age, and the same occurred for LVIDd (left ventricle internal diameter in diastole), LVFWd (left ventricular free wall thickness in diastole), IVSs (interventricular septum thickness in systole), LVIDs (left ventricle internal diameter in systole) and LVFWs (left ventricular free wall thickness in systole). There were differences in the size of the LA, Ao and LA/Ao ratio, which were greater at 90 days and 120 days of age. Echocardiographic changes accompany the development of lambs, where changes in echocardiographic parameters are evident with advancing age. The echocardiographic measurements in lambs obtained in the present study are similar to those in newborns.

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.

Spironolactone effect on cardiac structure and function of patients with heart failure and preserved ejection fraction: a pooled analysis of three randomized trials.

Spironolactone is currently used in a large proportion of patients with heart failure and preserved ejection fraction (HFpEF), yet its effect on cardiac structure and function in a large population has not been well established. The aim of this study was to evaluate the impact of spironolactone on key echocardiographic parameters in HFpEF. An individual-patient-data meta-analysis of three randomized trials (HOMAGE, Aldo-DHF, and TOPCAT) was performed comparing spironolactone (9-12 month exposure) to placebo (or control) for the changes in left atrial volume index (LAVi), left ventricular mass index (LVMi), interventricular septum (IVS) thickness, E/e' ratio, and left ventricular ejection fraction (LVEF) among patients with stage B (HOMAGE) or C (Aldo-DHF and TOPCAT) HFpEF. Analysis of covariance was used to test the effect of spironolactone on echocardiographic changes. A total of 984 patients were included in this analysis: 452 (45.9%) from HOMAGE, 398 (40.4%) from Aldo-DHF, and 134 (13.6%) from TOPCAT. The pooled-cohort patient's median age was 71 (66-77) years and 39% were women. Median LAVi was 29 (24-35)ml/m2 , LVMi 100 (84-118) g/m2 , IVS thickness 12 (10-13)mm, E/e' ratio 11 (9-13), and LVEF 64 (59-69)%. Spironolactone reduced LAVi by -1.1 (-2.0 to -0.1) ml/m2 (p=0.03); LVMi by -3.6 (-6.4 to -0.8)g/m2 (p=0.01); IVS thickness by -0.2 (-0.3 to -0.1)mm (p=0.01); E/e' ratio by -1.3 (-2.4 to -0.2) (p=0.02); and increased LVEF by 1.7 (0.8-2.6)% (p < 0.01). No treatment-by-study heterogeneity was found except for E/e' ratio with a larger effect in Aldo-DHF and TOPCAT (interaction p < 0.01). Spironolactone improved cardiac structure and function of patients with HFpEF.

Abstract 9337: The Association of Echo Parameters With Health Status in Patients With Obstructive Hypertrophic Cardiomyopathy. Insights From the Explorer-HCM Trial

Introduction: The EXPLORER-HCM trial showed mavacamten, a direct cardiac myosin inhibitor, improved the health status of patients with obstructive hypertrophic cardiomyopathy (HCM). To explore physiologic mechanisms for this improvement, we examined cross-sectional and longitudinal associations of echocardiographic parameters with health status. Methods: EXPLORER-HCM was a 13-country, double-blind randomized trial of mavacamten or placebo for 30 weeks in symptomatic patients with obstructive HCM and peak LVOT gradient ≥50 mmHg. Health status was assessed with the Kansas City Cardiomyopathy Questionnaire-overall summary score (KCCQ-OS, range 0-100, higher=better). Using a series of multivariable linear regression models, we examined the association of 1) echo parameters with KCCQ-OS at baseline and 2) change in echo parameters with change in KCCQ-OS. Nonlinear associations were explored with cubic splines. As this was a mechanistic analysis, treatment was not included. Results: Among 196 patients (mean age 58±12 years, 39% women), mean KCCQ-OS was 67±18 at baseline and 76±19 at 30 weeks; mean change of 10±16 points. At baseline, only interventricular septal thickness (IVST) was significantly associated with KCCQ-OS in adjusted analyses (1.2-point decrease in KCCQ-OS per 1 mm higher IVST; 95% CI -2.2 to -0.2, p=0.015). However, when comparing changes in echo parameters with changes in KCCQ-os, decreases in LVOT gradient at rest, LVOT gradient post-exercise, LVOT gradient with Valsalva, LV mass, posterior wall thickness, and IVST were each associated with significant improvements in KCCQ-OS (FIGURE). Measures of diastolic function were not associated with KCCQ-OS, either cross-sectionally or longitudinally. Conclusions: Among patients with obstructive HCM, reductions in LVOT gradients, LV mass, and wall thickness (IVST&gt;posterior wall) were associated with significant improvements in patients’ symptoms, function, and quality of life.

Abstract 10310: Sudden Cardiac Death in Recently Diagnosed Patients With Light-Chain Cardiac Amyloidosis

Introduction: Untreated, light-chain (AL) cardiac amyloidosis is associated with a median survival of 6-months when diagnosed in advanced stage. However, current plasma cell-targeting therapies have drastically improved end-organ function and life expectancy. Yet, a portion still die despite appropriate treatment. We hypothesize this is from sudden cardiac death (SCD). Aim: To determine the incidence of and clinical characteristics associated with 90-day SCD after diagnosis of AL amyloidosis. Methods: Clinical, electrocardiographic, imaging, treatment, and outcomes were abstracted from consecutive patients diagnosed with AL amyloidosis from 2014-2022 at UT Southwestern Medical Center. Statistics were reported as mean and standard deviation. Results: In our study cohort (N=189) patients with AL amyloidosis, 18 patients (66% male, age 65 ± 9.5 y) died by 90-days (9.5%). Of these, 14 patients died by 60-days (7.3%), and 10 patient died by 30-days (5.2%). There were 7 cardiac deaths (3.6%): including one PEA arrest (0.5%), one in-hospital cardiac arrest (0.5%) and five unwitnessed out-of-hospital cardiac arrests (2.6%). Among cardiac deaths, 3 patients had endomyocardial tissue consistent with AL. Revised Mayo Stage was 66% III, 33% IV. Six patients had at least one dose of chemotherapy with bortezomib, cyclophosphamide and dexamethasone (CyBorD), Velcade/Dexamethasone, or Daratumumab/CyBorD, and 5 had at least one full cycle. The LVEF was 48.9 ± 8.1, QTc 483 ± 50 ms, interventricular septal thickness was 1.2 cm ± 0.4 cm. CMR was obtained in 4 of 7 patients, with late gadolinium enhancement present in a diffuse pattern in 75%, average LVEDV 59 ± 9.5 mL. Mean time to death was 37.2 ± 21 days. Conclusions: Sudden cardiac death may be a significant contributor to mortality among patients with newly diagnosed AL amyloidosis. These observations warrant confirmation in larger cohorts and may identify an unmet need to enhance risk stratification for SCD in this population.

Abstract 10063: Changes in Clinical Phenotype of Patients With ATTR Cardiac Amyloidosis During the Past 20 Years

Introduction: Diagnostic and therapeutic advances have led to increased awareness of transthyretin cardiac amyloidosis (ATTR-CA). We sought to characterise the change in clinical phenotype of patients with ATTR-CA over the last 20-years. Methods: We studied 1967 patients diagnosed with ATTR-CA at the National Amyloidosis Centre (NAC) from 2002-2021. Results: Analysis by 5-year quartiles revealed a substantial incremental increase in patients diagnosed, with the most marked increases seen in wild-type ATTR. Increased diagnoses were accompanied by greater proportions of patients referred following bone scintigraphy and cardiac magnetic resonance imaging (3% vs 44% vs 67% vs 76%, P&lt;0.001). Over time, median duration of symptoms prior to diagnosis diminished from 36-months between 2002-2006 to 12-months between 2017-2021 (P&lt;0.001) and a greater proportion of patients had milder disease at the time of diagnosis across the 5-yearly quartiles (NAC stage 1: 34% vs 42% vs 44% vs 53%, P&lt;0.001). The latter was associated with more favourable echocardiographic parameters of structure and function, including an incremental decrease in interventricular septal thickness(18.0±3.8mm vs 17.2±2.6mm vs 16.9±2.3mm vs 16.6±2.4mm, P=0.01), which was associated with improved survival. The improved survival associated with the year of diagnosis remained significant when censoring at trial or disease modifying medication start date (2012-2016 vs. 2017-2021: HR=1.05, 95%CI[1.03-1.07], P&lt;0.001). Conclusions: Increased awareness and advances in cardiac imaging have been associated with a substantial increase in diagnosis of ATTR-CA and at a progressively earlier stage of the disease, which has contributed to improved survival in recent years. These changes may have important implications for initiation and outcome of therapy and urgently need to be factored into clinical trial design.

Abstract 13367: APOE ε4 Carriage Associates With Improved Myocardial Performance in Older Age

Introduction: Although APOE ε 4 allele carriage confers a risk of coronary disease, its persistence in human populations might be explained by certain survival advantages (antagonistic pleiotropy) . Hypothesis: Combining data from two British cohorts– the 1946 National Survey of Health and Development (NSHD) and Southall and Brent Revised (SABRE)–we explored whether APOE ε 4 carriage associates with beneficial or unfavorable left ventricular (LV) structural and functional echocardiography parameters in older age. Methods: Based on the presence of APOE ε 4, genotypes were divided into: APOE ε 4 (ε2ε4, ε3ε4, ε 4 ε 4) and non- APOE ε 4 carriers. Echocardiographic data included: LV ejection fraction, E/e’, systolic and diastolic posterior wall and interventricular septal thickness (LVPWT s/d , IVS s/d ), LV mass and the ratio of the LV stroke volume to the LV myocardial volume called myocardial contraction fraction (MCF). Generalized linear models explored associations between APOE ε 4 genotypes as exposures and echocardiographic biomarkers as outcomes. As APOE genotype is a genetic instrumental variable (unconfounded), Model 1 was unadjusted. Model 2 was adjusted for factors associated with the outcome (sex and socio-economic position) to yield more precise estimates; subsequent models were individually adjusted for mediators (body mass index, cardiovascular disease [CVD], high cholesterol and hypertension) to explore mechanistic pathways. Random-effects meta-analyses were performed across the cohorts. Results: 2596 participants were included. Compared to non- APOE ε 4 carriers, APOE ε 4 carriers had similar cardiac phenotypes in terms of EF, E/e’, LVPWT s/d , IVS s/d and LV mass but had a 4% higher MCF (95% confidence interval [CI]: 1–7%, p =0.016) which persisted in Model 2 (95% CI 1–7%, p =0.008) but was attenuated to 3% after adjustment for CVD, diabetes and hypertension (all 95% CI 0–6% all p &lt;0.070). Conclusions: APOE ε 4 carriage associates with improved myocardial performance in older age resulting in greater LV stroke volume generation per 1 mL of myocardium. This potentially favorable cardiac phenotype adds to the growing number of reported survival advantages attributed to APOE ε4 carriage that might collectively explain its persistence in humans.

Maternal obesity in pregnancy and children's cardiac function and structure: A systematic review and meta-analysis of evidence from human studies.

The prevalence of obesity is increasing worldwide. Experimental animal studies demonstrate that maternal obesity during pregnancy directly affects cardiac structure and function in their offspring, which could contribute to their increased cardiovascular disease (CVD) risk. Currently, a systematic overview of the available evidence regarding maternal obesity and alterations in cardiac structure and function in human offspring is lacking. We systematically searched the electronic databases Embase, MEDLINE and NARCIS from inception to June 29, 2022 including human studies comparing cardiac structure and function from fetal life onwards in offspring of women with and without obesity. The review protocol was registered with PROSPERO International Prospective Register of Systematic Reviews (identifier: CRD42019125071). Risk of bias was assessed using a modified Newcastle-Ottawa scale. Results were expressed using standardized mean differences (SMD). The search yielded 1589 unique publications, of which thirteen articles were included. Compared to offspring of women without obesity, fetuses of women with obesity had lower left ventricular strain, indicative of reduced systolic function, that persisted in infancy (SMD -2.4, 95% confidence interval (CI) -4.4 standard deviation (SD) to -0.4 SD during fetal life and SMD -1.0, 95% CI -1.6 SD to -0.3 SD in infancy). Furthermore, infants born to women with obesity had a thicker interventricular septum (SMD 0.6 SD, 95% CI 0.0 to 1.2 SD) than children born to women without obesity. In conclusion, cardiac structure and function differs between fetuses and children of women with and without obesity. Some of these differences were present in fetal life, persisted in childhood and are consistent with increased CVD risk. Long-term follow-up research is warranted, as studies in offspring of older age are lacking.