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This study assessed the impact of sweetened alcohol and naringin on cardiac function in Sprague-Dawley rats. Male (n = 40) and female (n = 40) rats were allocated to control, sweetened alcohol (SOH), naringin (NA), and sweetened alcohol with naringin (SOH + NA) groups. SOH and SOH + NA rats received 10% alcohol + 20% fructose in gelatine; SOH + NA and NA rats received 50 mg/kg naringin in gelatine daily for 10 weeks. Echocardiography was performed to assess left ventricular (LV) function. LV cardiomyocyte diameters and collagen area fraction were determined by H&E and picrosirius-red staining, respectively. In males, sweetened alcohol and naringin did not affect cardiac function. Female SOH rats had increased LV end-diastolic posterior wall (p = 0.04), relative wall thicknesses (p = 0.01), and LV cardiomyocyte diameters (p = 0.005) compared with control. Female SOH and SOH + NA had reduced lateral e' and e'/a' and increased E/e' (p < 0.0001). Female SOH (p = 0.01) and SOH + NA (p = 0.04) rats had increased LV collagen area fraction compared with controls. In males, neither sweetened alcohol nor naringin affected cardiac geometry or diastolic function. In females, sweetened alcohol induced concentric remodelling, impaired LV relaxation, and elevated filling pressures. Naringin may have the potential to improve the sweetened alcohol-induced concentric remodelling; however, it did not ameliorate diastolic dysfunction in females.

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BACKGROUND: Although diastolic dysfunction is the main pathophysiological feature of hypertrophic cardiomyopathy (HCM), it remains to be clarified whether parameters of diastolic function can reliably determine HCM prognosis. In patients with reduced left ventricular (LV) distensibility, chronic elevation of LV diastolic pressure is seen with a smaller than expected LV size. Accordingly, patients with HCM with severe LV diastolic dysfunction typically demonstrate left atrial (LA) dilation and a disproportionately smaller left ventricle. Therefore, we investigated the relationship between LA/LV diameter ratio, as a potential indicator of disease progression, and outcomes in patients with HCM. METHODS: We included 468 patients in whom LA and LV end-diastolic diameter were successfully evaluated by echocardiography at the initial assessment. We divided the patients into two groups: those with an LA/LV diameter ratio > 1 and those with an LA/LV diameter ratio ≤ 1. We compared the HCM-related death rates between the two groups. RESULTS: Of the 468 patients, 96 patients (20.5 %) with HCM showed an LA/LV diameter ratio > 1. In the univariate analysis, patients with an LA/LV diameter ratio > 1 had a significantly greater likelihood of HCM-related death than patients with an LA/LV diameter ratio ≤ 1 (log-rank p = 0.002). In the multivariate Cox proportional hazards analysis, when including LA/LV diameter ratio > 1 and imbalanced baseline variables, an LA/LV diameter ratio > 1 was an independent determinant of HCM-related death (adjusted hazard ratio: 1.87, 95 % confidence interval: 1.08-3.24; p = 0.024). CONCLUSION: LA/LV diameter ratio can be easily evaluated and may be useful for risk stratification of HCM-related death in patients with HCM.

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BACKGROUND: In quantifying left ventricular (LV) diameter, which position for echocardiographic measurements, mitral valve tip level (MV-tip) or LV mid level (LV-mid), more accurately represents the LV volume is unclear. Furthermore, which factor affects the measurement error also has not been elucidated. METHODS: We enrolled 150 patients without myocardial infarction and local asynergy who underwent echocardiography and cardiac magnetic resonance imaging (CMRI). Echocardiographic LV diastolic diameter (LVDD) and LV systolic diameter (LVDS) were measured at both MV-tip and LV-mid, and the LV end-diastolic volume (LVEDV) and end-systolic volume (LVESV) were quantified using CMRI. We quantified the degree of aortic wedging as the angle between the anterior wall of the aorta and the ventricular septal surface (ASA). RESULTS: The average LVDD was smaller and average LVDS larger when measured at the MV-tip than at the LV-mid. In regression analyses, the correlation coefficient between LVDD and LVEDV was larger at LV-mid (R = 0.89) than at MV-tip (R = 0.82), and the correlation coefficient between LVDS and LVESV also larger at LV-mid (R = 0.93) than MV-tip (R = 0.87). ASA, Valsalva diameter, left atrial diameter, patient height, and LV mass significantly affected the echocardiographic measurement error, but no factor affected the measurement error when quantifying LVDD at the LV-mid level. CONCLUSIONS: The echocardiographic LV diameter measured at LV-mid has a stronger correlation with LV chamber size derived from CMRI than measurements at MV-tip. The LVDD measured at the LV-mid level is not affected by other factors.

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Aims: This study aims to investigate the association between left ventricular diastolic dysfunction (LVDD) and epicardial adipose tissue (EAT) accumulation in patients with chronic coronary syndrome (CCS) and preserved left ventricular ejection fraction (LVEF). Methods and results: The study included 314 patients with preserved LVEF who underwent coronary computed tomographic angiography (CCTA) and thoracic tissue Doppler echocardiography (TTDE). The EAT volume was measured using CCTA. LVDD was categorized into three groups: absent LVDD, undetermined LVDD, and LVDD. Multivariate logistic regression analysis was performed to assess the association between the clinical parameters, TTDE and CCTA findings, and LVDD. Patients (mean age: 66 ± 13 years; 52% men) were divided into LVDD present (30 patients, 9.6%), LVDD absent (219 patients, 69.7%), and LVDD undetermined (65 patients, 20.7%) groups. CCTA showed that patients with LVDD had a significantly higher coronary artery calcium (CAC) score and % plaque volume (%PV) than those without LVDD, whereas the prevalence of obstructive coronary artery disease was comparable between the groups. The EAT volume index correlated with each LVDD diagnostic component, except for tricuspid regurgitation velocity. A multivariate model showed that age [odds ratio (OR), 1.13; P < 0.001] and EAT volume index (OR, 1.02; P = 0.038) were independently associated with LVDD, even after adjusting for left ventricular mass index (OR, 1.05; P = 0.005). There was no significant association between the CAC score and %PV or LVDD. Conclusion: This study demonstrated that EAT volume index and left ventricular mass index were robust predictors of LVDD; however, there was no independent association between coronary atherosclerotic disease burden and LVDD.

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Cardiac allografts suffer diastolic dysfunction early post-heart transplantation (HTx) due to ischemic injury, however the natural course of diastology recovery post HTx remains unknown (Tallaj et al., 2007 [1]). We retrospectively reviewed 60 adult HTx patients between 2015 and 2021 at a single site. Invasive hemodynamics and echocardiograms were obtained at 2 weeks and 1, 3, 6, and 12 months post-HTx. RA strain by 2D feature tracking was compared to intracardiac pressure measurements. In all patients, we observed normalization of RV and RA filling pressures by post-operative week 12 and recovery of diastolic dysfunction by month 6. There was an inverse correlation between RV end-diastolic pressure and RA contractile (r = -0.192, p < 0.05) and reservoir (r = -0.128, p < 0.05) functions in the allograft. As the post-transplant care paradigm shifts away from invasive procedures, right atrial indices should be included in imaging-based allograft surveillance studies.

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AIMS: Echocardiographic diastolic parameters are used to diagnose and monitor increased left ventricular filling pressure (LVFP) and we hypothesized that increased loading conditions cause increased E/e'. Our aim was to assess the effect of preload augmentation on diastolic parameters among both healthy subjects and subjects with known cardiac disease. METHODS AND RESULTS: We included 129 subjects merged from two cohorts; one dialysis cohort (n = 47) and one infusion cohort (n = 82). Echocardiography was performed immediately before and after hemodialysis (HD) or saline infusion, under low and high loading conditions. Elevated LVFP was defined as septal E/e' ≥ 15 and/or lateral E/e' ≥ 13 at high-loading conditions. The population was divided according to elevated LVFP (n = 31) and normal LVFP (n = 98). The load difference for the population was 972 ± 460 mL, with no differences in load difference between elevated and normal LVFP (p NS). The subjects with elevated LVFP were older (63 ± 11 vs. 46 ± 16 years, p < .001), and had lower LV ejection fraction (50 ± 14 vs. 59 ± 8.1%, p < .01). After augmented preload, EDV increased in the normal LVFP group (p < .01) but remained unchanged in the elevated LVFP group (p NS). Both E and e' increased among the subjects with normal LVFP, whereas E/e' remained unchanged (∆E/e' +.1 [-.5-1.2]), p NS). Among the subjects with elevated, LVFP we observed increased E but not e', resulting in significantly increased E/e' (∆ average E/e' +2.4 [0-4.0], p < .01). CONCLUSION: Augmented preload does not seem to affect E/e' among subjects with normal LVFP, whereas E/e' seems to increase significantly among subjects with elevated LVFP.

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CONTEXT: Numerous studies have demonstrated the positive effects on metabolic factors of consuming chia seeds. However, the results of clinical trials have been inconsistent. OBJECTIVE: The aim of this study was to conduct a systematic review and meta-analysis of available randomized controlled trials to explore the effects of chia seed consumption on body weight (BW), body composition, blood pressure, and glycemic control. DATA SOURCES: A comprehensive search was conducted on the Scopus, PubMed, Medline via Ovid, ISI Web of Science, and Scholar Google databases up to August 2023. DATA EXTRACTION: The outcomes of interest included systolic blood pressure (SBP), diastolic blood pressure (DBP), BW, body mass index (BMI), body fat percentage, waist circumference (WC), fasting blood glucose (FBG), and hemoglobin A1c (HbA1c). DATA ANALYSIS: Weighted mean difference (WMD) and 95% CIs were used to determine the effect size. RESULTS: A total of 8 eligible studies were included in the analysis. The findings revealed a significant reduction in SBP (WMD: -7.19 mmHg; 95% CI, -10.63 to -3.73; P < .001) and DBP (WMD: -6.04 mmHg, 95% CI, -9.58 to -2.49; P = .001). However, no significant effects were observed on BW, body fat percentage, WC, BMI, FBG, and HbA1c. Subgroup analysis indicated that the effect of chia seed on SBP was significant in participants with a baseline SBP of less than 140 mmHg, but the effect was not dependent on the administered dose. CONCLUSION: Chia seed consumption has positive effects on SBP and DBP but does not significantly impact BW, body composition, or glycemic parameters. However, the limited amount of data from included studies should be considered as a limitation while interpreting these findings. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. CRD42023462575.

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Heart failure with preserved ejection fraction (HFpEF) includes almost half of heart failure cases typified by a specific clinical syndrome. Despite diagnostic and management advances, HFpEF still presents a diagnostic challenge and a paucity of therapies specifically aimed at enhancing survival and improving quality of life is still lacking. This review elucidates the diagnostic complexity of HFpEF, highlighting the use of both subjective and objective criteria within algorithmic frameworks. It also examines the significant impact of comorbidities on the progression of HFpEF. Additionally, we explore the latest evidence on targeting these comorbidities therapeutically, although the benefits to mortality are still limited.

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PURPOSE: Regional anaesthesia techniques provide highly effective alternative to general anaesthesia. Existing evidence on the effect of spinal anaesthesia (SA) on cardiac diastolic function is scarce. This study aimed to evaluate the effects of a single-injection, low-dose SA on left ventricular end-diastolic pressures (LVEDP) using echocardiography in euvolaemic patients undergoing elective vascular surgery. METHODS: This is a prospective study in adult patients undergoing elective vascular surgery with SA. Patients with contraindications for SA or significant valvular disease were excluded. During patients' evaluations fluid administration was targeted using arterial waveform monitoring. All patients underwent echocardiographic studies before and after SA for the assessment of indices reflective of diastolic function. LVEDP was evaluated using the E/e' ratio. Blood samples were drawn to measure troponin and brain natriuretic peptide (BNP) levels before and after SA. RESULTS: A total of 62 patients (88.7% males, 71.00 ± 9.42 years) were included in the analysis. In total population, end-diastolic volume (EDV, 147.51 ± 41.36 vs 141.72 ± 40.13 ml; p = 0.044), end-systolic volume (ESV, 69.50 [51.50] vs 65.00 [29.50] ml; p < 0.001) and E/e' ratio significantly decreased (10.80 [4.21] vs. 9.55 [3.91]; p = 0.019). In patients with elevated compared to those with normal LVEDP, an overall improvement in diastolic function was noted. The A increased (- 6.58 ± 11.12 vs. 6.46 ± 16.10; p < 0.001) and E/A decreased (0.02 ± 0.21 vs. - 0.36 ± 0.90; p = 0.004) only in the elevated LVEDP group. Patients with elevated LVEDP had a greater decrease in E/e' compared to those with normal LVEDP (- 0.03 ± 2.39 vs. - 2.27 ± 2.92; p = 0.002). CONCLUSION: This study in euvolaemic patients undergoing elective vascular surgery provides evidence that SA improved LVEDP.

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Listeria monocytogenes is a rare and often fatal cause of pericarditis. This paper presents a patient with heart failure with preserved ejection fraction, CD4+ T-cell deficiency, and L monocytogenes constrictive pericarditis. This case highlights a rare association between heart failure and immunodeficiency, in addition to the multidisciplinary management of constrictive pericarditis.

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Heart failure with preserved ejection fraction (HFpEF) and atrial fibrillation (AF) are comorbid conditions that are increasingly prevalent and have a high socioeconomic burden. This article discusses their shared pathophysiology, focusing on the triad of hypertension, obesity, and aging. We highlight the misperception that pharmacologic heart rate lowering is beneficial, which has resulted in an overprescription of beta-blockers in HFpEF and AF. In contrast, heart rate modulation through accelerated pacing provides hemodynamic and structural advantages, which have yielded significant improvements in quality of life, physical activity, and AF burden in the myPACE trial of patients with preclinical or overt HFpEF.

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BACKGROUND: Renal denervation (RDN) is an innovative procedure designed to regulate the renal sympathetic nervous system for the control of arterial hypertension (HTN). RDN has emerged as an alternative for patients with resistant HTN. However, the clinical efficacy of RDN remains incompletely elucidated. METHODS: PubMed, Embase, and Cochrane databases were searched for randomized controlled trials (RCTs) comparing the use of RDN with sham procedure or pharmacological treatment in patients with resistant HTN. Statistical analyses were performed using R Studio 4.3.2 (R Foundation for Statistical Computing, Vienna, Austria). Heterogeneity was examined with the Cochran Q test I2 statistics. Mean difference (MD) with 95% confidence interval (CI) were pooled across trials. P values of <0.05 were considered statistically significant. The primary outcomes of interest were changes from baseline in systolic blood pressure (SBP), diastolic blood pressure (DBP), and serum creatinine. RESULTS: Twenty-one RCTs comprising 3345 patients were included in this meta-analysis, whereby 2004 (59.91%) received renal denervation and 1341 (40.09%) received pharmacological treatment or sham procedure. Follow-up ranged from 2 to 48 months. Compared to control group, RDN significantly reduced SBP (MD -3.53 mm Hg; 95% CI -5.94 to -1.12; p = 0.004; I2 = 74%) and DBP (MD -1.48 mm Hg; 95% CI -2.56 to -0.40; p = 0.007; I2 = 51%). Regarding serum creatinine (MD -2.51; 95% CI -7.90 to 2.87; p = 0.36; I2 = 40%), there was no significant difference between RDN and control groups. CONCLUSION: In this meta-analysis of RCTs of patients with resistant HTN, RDN was associated with a reduction in SBP and DBP compared to sham procedure or pharmacological treatment.

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The effect of cooking aerosol on the human heart was investigated in this study. The heart rate and blood pressure of 33 healthy adults were monitored before, exactly after, and two hours post-exposure (30 minutes, 60 minutes, 90 minutes, and 120 minutes after cooking). One hundred twenty grams of ground beef was fried in sunflower oil for twenty minutes using a gas stove without ventilation. Ultrafine particles, indoor temperature, relative humidity, carbon dioxide, oil, and meat temperatures were monitored during the experiment. The average particle emission rate (S) and average decay rate (a+k) for meat frying were found to be 2.09×1013 (SD=3.94 ×1013, R2=0.98, P <0.0001) particles/min, and 0.055 (SD=0.019, R2=0.91, P <0.0001) particles/min, respectively. No statistically significant changes in diastolic blood pressure (DBP) and heart rate (HR) were observed. The average systolic blood pressure (SBP) statistically significantly increased from 98 mmHg (before the exposure) to 106 mmHg 60 minutes after the exposure. The results suggested that frying emission statistically significantly impacted blood pressure.

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Background: The benefit of pulmonary vein isolation (PVI) in patients with atrial fibrillation (AF) and heart failure with reduced ejection fraction (HFrEF) is well established; its efficacy in patients with heart failure preserved ejection fraction (HFpEF) is less clear. Objective: The objective of the study was to compare AF and heart failure (HF) rehospitalizations after PVI in patients with HFpEF vs HFrEF. Methods: The IBM MarketScan Database was used to identify patients undergoing PVI for AF. Patients were categorized by HF status: absence of HF, presence of HFrEF, or presence of HFpEF. Primary outcomes were HF and arrhythmia hospitalizations after PVI. Results: A total of 32,524 patients were analyzed: 27,900 with no HF (86%), 2948 with HFrEF (9%), and 1676 with HFpEF (5%). Compared with those with no HF, both patients with HFrEF and HFpEF were more likely to be hospitalized for HF (hazard ratio [HR] 7.27; P < .01 for HFrEF and HR 9.46; P < .01 for HFpEF) and for AF (HR 1.17; P < .01 for HFrEF and HR 1.74; P < .01 for HFpEF) after PVI. In matched analysis, 23% of patients with HFrEF and 24% patients with HFpEF demonstrated a reduction in HF hospitalizations (P = .31) and approximately one-third demonstrated decreased arrhythmia rehospitalizations (P = .57) in the 6 months after PVI. Compared with those with HFrEF in longer-term follow-up (>1 year), patients with HFpEF were more likely to have HF (HR 1.30; P < .01) and arrhythmia (HR 1.19; P < .01) rehospitalizations. Conclusion: Reductions in HF and arrhythmia hospitalizations are observed early after PVI across all patients with HF, but patients with HFpEF demonstrate higher HF rehospitalization and arrhythmia recurrence in longer-term follow-up than do patients with HFrEF.

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BACKGROUND: During the COVID-19 pandemic sex-related differences concerning the spectrum of cardiovascular complications have been observed in the acute infection, and during recovery. This study aims to emphasize sex-related disparities regarding left ventricular systolic function (LVSF), right ventricular function (RVF), diastolic dysfunction (DD), and pericardial pathologies during the post-COVID-19 syndrome. METHODS: 274 patients with post-acute COVID-19 syndrome, 127 men and 147 women, aged under 55, were evaluated within 90 days after the acute illness and followed at 3 and 6 months. RESULTS: Based on detailed transthoracic echocardiography (TTE), we identified significantly more frequently (p˂0.001) altered LVSF in men, while in women impaired RVF, and DD were significantly more common (p˂0.001). Pericardial impairment did not seem to be influenced by gender. The TTE parameters characterizing these patterns were correlated with the severity of the initial infection and the time elapsed since and alleviated in time. The multivariate regression analysis confirmed these sex-related associations and their impact on patients' functional status. CONCLUSIONS: Male patients had a higher tendency to develop altered LVSF, while female subjects had more frequently impaired RVF and DD. These abnormalities alleviated in time and exerted a significant influence on patients' functional status.

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Left ventricular diastolic dysfunction (LVDD) commonly coexists with kidney dysfunction. In this study, we investigated the presence of abnormalities in echocardiography parameters indicative of LVDD across stages of kidney function. Methods: We selected patients who visited a university hospital and had a serum creatinine and echocardiography reported in their medical records. Participants were categorized based on their kidney function: normal (estimated glomerular filtration rate [eGFR] ≥ 90 mL/min/1.73 m2), mildly decreased (eGFR: 60-90), moderately decreased (eGFR: 30-60), and severely decreased (eGFR < 30). The relationship between kidney function and echocardiography parameters was examined using logistic and linear regressions. Results: Among 4022 patients (age: 66.5 years [SD: 12.1], 41% women), 26%, 50%, 20%, and 4% had a normal, mildly, moderately, and severely decreased kidney function, respectively. Compared to patients with normal kidney function, patients with mildly decreased kidney function had higher odds for an abnormal E/e' ratio (OR: 1.51 [95% CI: 1.13, 2.02]). Patients with moderately decreased kidney function presented a higher risk of abnormal E/e' (OR: 2.90 [95% CI: 2.08, 4.04]), LAVI (OR: 1.62 [95% CI: 1.13, 2.33]), TR velocity (OR: 2.31 [95% CI: 1.49, 3.57]), and LVMI (OR: 1.70 [95% CI: 1.31, 2.20]), while patients with severely decreased kidney function had higher odds for abnormal E/e' (OR: 2.95 [95% CI: 1.68, 5.17]) and LVMI > 95 g/m2 in women or >115 g/m2 in men (OR: 2.07 [95% CI: 1.27, 3.38]). The linear regression showed a significant inverse association between eGFR and echocardiography parameters, meaning that with worse kidney function, the parameters for LVDD worsened as well. Conclusions: Abnormal echocardiography parameters of LVDD were present even in patients with mildly decreased kidney function. As the kidney function worsened, there was a gradual increase in the risk of abnormal parameters of LVDD.

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BACKGROUND: Prematurely born adults have increased risk for cardiovascular disease. There are limited cardiac data on US-born preterm individuals. We aimed to determine whether adolescents and adults born prematurely have altered left ventricular (LV) structure and function, and to interrogate diastolic function using isometric handgrip exercise. METHODS AND RESULTS: Adolescents and adults born moderately to extremely preterm (≤32 weeks gestation or <1500 g birth weight) were recruited from the Parkland Health Neonatal Intensive Care Unit Registry. Full-term participants were recruited from the local area. Study procedures included anthropometrics and vitals, handgrip testing, and echocardiography performed at rest and during isometric handgrip exercise. Data were reported as mean±SD. The study enrolled 107 preterm and 48 term participants. Preterm participants (gestational age: 29.5±2.5 weeks) were shorter with higher body mass index (P<0.001) compared with term participants. Preterm participants exhibited smaller LV end-diastolic volume index (50.8±10.1 versus 56.9±10.0 mL/m2, P<0.001), LV stroke volume index (29.6±6.0 versus 34.1±6.5 mL/m2, P<0.001), and LV mass index (67.2±13.1 versus 73.3±14.2 g/m2, P=0.002) compared with term individuals. Preterm participants also had subclinical reductions in LV peak systolic tissue velocity and peak early diastolic tissue velocity lateral at rest. Isometric handgrip exercise promoted a reduction in diastolic function and an increase in hemodynamic measures, but changes during isometric handgrip exercise were similar between groups. CONCLUSIONS: Adolescents and adults born preterm exhibit overall normal cardiac function despite smaller cardiac volumes and mass compared with individuals born full term. Effects are most pronounced at the lowest gestational ages.

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Heart failure is a complex clinical manifestation due to diastolic dysfunction and systolic dysfunction of the left ventricle (LV). Diastolic dysfunction of the LV plays an important role in worsening the quality of life (QoL) in heart failure patients. The aim of this study was to assess the relationship between the severity or grade of LV diastolic dysfunction and QoL in heart failure with reduced ejection fraction (HFrEF) patients. A retrospective cohort study was conducted at the Cardiac Center of H. Adam Malik Hospital, Medan, Indonesia, from January 2022 to December 2022. This study included inpatients and outpatients aged above 18 years who were diagnosed with HFrEF, identified by echocardiography with an ejection fraction of ≤40%. Echocardiography was performed to evaluate left ventricular diastolic dysfunction, and QoL was assessed using the Minnesota Living with Heart Failure Questionnaire (MLHFQ) 6-12 months after the severity of LV diastolic dysfunction was confirmed. The MLHFQ was classified into good and poor QoL. The severity of LV diastolic function was measured using the E/A ratio, mean E/e' ratio, tricuspid regurgitation velocity (TR Vmax), and left atrial volume index (LAVI), and was classified into grades I, II, and III. The relationships between the severity of diastolic dysfunction and other factors with QoL were measured using Chi-squared, Fisher's exact test, or Mann-Whitney test, as appropriate. A total of 96 patients were included in the study, of which 56 (58.3%) patients had grade I, 12 (12.5%) had grade II, and 28 (29.2%) patients had grade III of LV diastolic dysfunction. There were 77 (80.2%) and 19 (19.8%) patients with good and poor QoL, respectively. This study revealed a significant relationship between the severity of LV diastolic dysfunction and QoL in HFrEF patients with p=0.040. In conclusion, the degree of LV diastolic dysfunction is related to the QoL of HFrEF patients and therefore better comprehensive management strategies should be considered in HFrEF cases to address the impact of LV diastolic dysfunction on QoL.

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BACKGROUND: Assessing left ventricular diastolic function (LVDF) with echocardiography as per ASE guidelines is tedious and time-consuming. The study aims to develop a fully automatic approach of this procedure by a lightweight hybrid algorithm combining deep learning (DL) and machine learning (ML). METHODS: The model features multi-modality input and multi-task output, measuring LV ejection fraction (LVEF), left atrial end-systolic volume (LAESV), and Doppler parameters: mitral E wave velocity (E), A wave velocity (A), mitral annulus e' velocity (e'), and tricuspid regurgitation velocity (TRmax). The algorithm was trained and tested on two internal datasets (862 and 239 echocardiograms) and validated using three external datasets, including EchoNet-Dynamic and CAMUS. The ASE diastolic function decision tree and total probability theory were used to provide diastolic grading probabilities. RESULTS: The algorithm, named MMnet, demonstrated high accuracy in both test and validation datasets, with Dice coefficients for segmentation between 0.922 and 0.932 and classification accuracies between 0.9977 and 1.0. The mean absolute errors (MAEs) for LVEF and LAESV were 3.7 % and 5.8 ml, respectively, and for LVEF in external validation, MAEs ranged from 4.9 % to 5.6 %. The diastolic function grading accuracy was 0.88 with hard criteria and up to 0.98 with soft criteria which account for the top two probability in total probability theory. CONCLUSIONS: MMnet can automatically grade ASE diastolic function with high accuracy and efficiency by annotating 2D videos and Doppler images.

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BACKGROUND: Aficamten, a next-in-class cardiac myosin inhibitor, improved peak oxygen uptake (pVO2) and lowered resting and Valsalva left ventricular outflow (LVOT) gradients in adults with symptomatic obstructive hypertrophic cardiomyopathy (oHCM) in SEQUOIA-HCM (Phase 3 Trial to Evaluate the Efficacy and Safety of Aficamten Compared to Placebo in Adults With Symptomatic oHCM), a phase 3, multicenter, randomized, double-blinded, placebo-controlled study. OBJECTIVES: The authors sought to evaluate the effect of aficamten on echocardiographic measures of cardiac structure and function in SEQUOIA-HCM. METHODS: Serial echocardiograms were performed over 28 weeks in patients randomized to receive placebo or aficamten in up to 4 individually titrated escalating doses (5-20 mg daily) over 24 weeks based on Valsalva LVOT gradients and left ventricular ejection fraction (LVEF). RESULTS: Among 282 patients (mean age 59 ± 13 years; 41% female, 79% White, 19% Asian), mean LVEF was 75% ± 6% with resting and Valsalva LVOT gradients of 55 ± 30 mm Hg and 83 ± 32 mm Hg, respectively. Over 24 weeks, aficamten significantly lowered resting and Valsalva LVOT gradients, and improved left atrial volume index, lateral and septal e' velocities, and lateral and septal E/e' (all P ≤ 0.001). LV end-systolic volume increased and wall thickness decreased (all P ≤ 0.003). Aficamten resulted in a mild reversible decrease in LVEF (-4.8% [95% CI: -6.4 to -3.3]; P < 0.001) and absolute LV global circumferential strain (-3.7% [95% CI: 1.8-5.6]; P < 0.0010), whereas LV global longitudinal strain was unchanged. Several measures, including LVEF, LVOT gradients, and E/e' returned to baseline following washout. Among those treated with aficamten, improved pVO2 and reduction in N-terminal pro-B-type natriuretic peptide (NT-proBNP) were associated with improvement in lateral e' velocity and septal and lateral E/e' (all P < 0.03), whereas improvement in Kansas City Cardiomyopathy Questionnaire Clinical Summary Scores (KCCQ-CSS) was associated with a decrease in both LVOT gradients (all P < 0.001). CONCLUSIONS: Compared with placebo, patients receiving aficamten demonstrated significant improvement in LVOT gradients and measures of LV diastolic function, and several of these measures were associated with improvements in pVO2, KCCQ-CSS, and NT-proBNP. A modest decrease in LVEF occurred yet remained within normal range. These findings suggest aficamten improved multiple structural and physiological parameters in oHCM without significant adverse changes in LV systolic function. (Phase 3 Trial to Evaluate the Efficacy and Safety of Aficamten Compared to Placebo in Adults With Symptomatic oHCM [SEQUOIA-HCM]; NCT05186818).