Internal Diameter In Diastole Research Articles

Left atrial parameters predict incident atrial fibrillation and flutter in patients with heart failure with reduced ejection fraction

Abstract Background Left atrial (LA) function parameters have shown prognostic value in relation to incidence of atrial fibrillation in the general population, but this remains to be investigated in patients with heart failure with reduced ejection fraction (HFrEF). Purpose This study aimed to investigate the relationship between LA function parameters and the risk of incident atrial fibrillation/atrial flutter (AF/AFL) in patients with HFrEF. Methods Subjects free of AF/AFL were retrospectively included from a HF clinic and followed using the Danish National Patient Registry. Cox proportional hazards regression was used to assess the prognostic value of LA function parameters. These included LA ejection fraction (LAEF), peak atrial longitudinal strain (PALS), peak atrial contractile strain (PACS) and LA conduit strain (LACS). In addition, multivariable Cox regression was performed to adjust for demographic and echocardiographic parameters, including LA volume index (LAVi). The LA function parameters that remained significant in adjusted analysis were examined using cubic splines, and cutoff values corresponding to a hazard ratio (HR) equal to 1 were derived from these. Results The total study population consisted of 435 subjects with a left ventricular ejection fraction (LVEF) ≤45% (mean age 65.6±11.7 years, male sex 70.1%) free from AF/AFL at baseline. During a median follow-up of 11.4 years [IQR: 10.8, 14.2], 111 (25.5%) developed AF/AFL. Subjects who met the outcome were generally older (69.0±8.8 years vs. 64.4±12.4, p<0.001), had lower baseline heart rate, and a higher prevalence of moderate or severe valve disease (12.6% vs. 3.1%, p<0.001). They also had higher LV mass index and LV internal diastolic diameter index, but similar LVEF. These subjects had larger LAVi (30 ml/m2 [IQR: 24, 38] vs. 26 ml/m2 [IQR: 20, 32], p<0.001), while LAEF (33±14.8% vs. 39±14.9%, p<0.001), PALS (20.3% [IQR: 16.2, 26.5] vs. 23.2% [IQR: 18.6, 29.6], p=0.001), and PACS (9.7% [IQR: 6.9, 13.5] vs. 12.0% [IQR: 7.8, 16.4], p=0.004) were all significantly lower. LACS was similar between groups. In univariable Cox regression, all LA parameters were significant predictors of the AF/AFL (LAEF: HR 0.98 per 1% increase, 95% CI 0.96-0.99, p=0.0002, PALS: HR 0.96 per 1% increase, 95% CI 0.94–0.98, p=0.0008, PACS: HR 0.95 per 1%, 95% CI 0.93–0.98, p=0.0024, LACS: HR 0.96, 95% per 1% increase CI 0.92–0.998, p=0.039. In adjusted analysis, however, only LAEF (HR 0.98, 95% CI 0.976-0.995, p=0.0087) and PACS (HR 0.96, 95% CI 0.993–0.999, p=0.044) remained significant. Splines were constructed for LAEF and PACS (Figure 1), and a cutoff for increased risk of AF/AFL at 38% for LAEF and 12% for PACS, respectively, were derived (Figure 2). Conclusion LAEF and PACS are associated with risk of incident AF/AFL in patients with HFrEF, independent of clinical and echocardiographic risk factors. Our results suggest an increased risk of AF/AFL at LAEF below 38% and PACS below 12%.Figure 1 SplinesFigure 2 Cumulative incident curves

The impact of ventricular remodeling on quality-of-life outcomes after Transcatheter aortic valve replacement

BackgroundAmong patients with aortic stenosis, ventricular remodeling by hypertrophy can limit the augmentation of flow with exertion, even after valve intervention. However, the effect of hypertrophy on quality of life (QoL) improvement has not been studied. We aimed to determine the effect of ventricular hypertrophy on QoL outcomes after transcatheter aortic valve replacement (TAVR). MethodsAll patients undergoing TAVR from 2011 to 2021 at our institution were included. Groups were divided into none/mild ventricular hypertrophy (non-remodeled, NR) and moderate/severe left ventricular hypertrophy (VH) according to guideline-recommended cut-offs for left ventricular (LV) wall thickness. The Kansas City Cardiomyopathy Questionnaire (KCCQ) was utilized to assess QoL; primary outcome was KCCQ change <5 from baseline to 30 days and 1 year. ResultsWe analyzed 679 patients (NR: N = 389, VH: N = 290). Groups differed by septal thickness (1.12 cm vs. 1.44 cm, p < 0.001), posterior wall thickness (1.08 cm vs. 1.33 cm, p < 0.001), and LV internal diastolic diameter (4.34 cm vs. 4.19 cm, p = 0.006). The primary outcome was similar between NR and VH at 30 days (31.6 % vs. 28.6 %, p = 0.449) and 1 year (27.7 % vs. 21.5 %, p = 0.217). NR and VH experienced similar proportions of worsening, no change, or small, moderate, and large improvements in KCCQ score. Both groups experienced similar domain score changes and New York Heart Association class improvement. A subgroup analysis of VH patients did not reveal interaction with cavity size or stroke volume. ConclusionPatients with significant ventricular remodeling by hypertrophy and aortic stenosis have similar QoL changes after intervention compared to patients without significant remodeling.

Loss of cardiomyocyte-specific adhesion G-protein-coupled receptor G1 (ADGRG1/GPR56) promotes pressure overload-induced heart failure.

Adhesion G-protein-coupled receptors (AGPCRs), containing large N-terminal ligand-binding domains for environmental mechano-sensing, have been increasingly recognized to play important roles in numerous physiologic and pathologic processes. However, their impact on the heart, which undergoes dynamic mechanical alterations in healthy and failing states, remains understudied. ADGRG1 (formerly known as GPR56) is widely expressed, including in skeletal muscle where it was previously shown to mediate mechanical overload-induced muscle hypertrophy; thus, we hypothesized that it could impact the development of cardiac dysfunction and remodeling in response to pressure overload. In this study, we generated a cardiomyocyte (CM)-specific ADGRG1 knockout mouse model, which, although not initially displaying features of cardiac dysfunction, does develop increased systolic and diastolic LV volumes and internal diameters over time. Notably, when challenged with chronic pressure overload, CM-specific ADGRG1 deletion accelerates cardiac dysfunction, concurrent with blunted CM hypertrophy, enhanced cardiac inflammation and increased mortality, suggesting that ADGRG1 plays an important role in the early adaptation to chronic cardiac stress. Altogether, the present study provides an important proof-of-concept that targeting CM-expressed AGPCRs may offer a new avenue for regulating the development of heart failure.

Mitral valve surgery in octogenarians: long-term and hemodynamic results.

Octogenarians are often denied mitral valve (MV) surgery secondary to concerns over increased perioperative morbidity and mortality. The objective of this study was to examine the outcomes of octogenarians undergoing mitral valve repair (MVr) and replacement (MVR). The outcomes of 139 patients between the ages of 80-90 who underwent MVR/MVr between 2004-2018 at the Mazankowski Alberta Heart Institute (Edmonton, AB, Canada) were retrospectively analyzed. Follow-up was extended to a maximum of 15.8 years. Following MVR, all-cause mortality at 30 days, 1 year, 5 years, 10 years, and the longest follow-up was 7%, 14%, 36.3%, 61.8%, and 67.7%, respectively. Post-MVr, all-cause mortality at the same time points was 1.9%, 7.6%, 22.5%, 55.5%, and 100%, respectively. During the Hospitalization Index, rates of new-onset atrial fibrillation, sepsis, acute kidney injury, superficial sternal wound infection, deep sternal wound infection, mediastinal bleeding, and permanent pacemaker insertion ranged from 22.1-34.0%, 3.8-11.0%, 7.6-22.0%, 1.9-2.4%, 0-1.2%, 0%, and 0-6.1%, respectively. Rates of overall rehospitalization, as well as readmission for heart failure, stroke, myocardial infarction, and MV reoperation ranged from 71.0-85.5%, 52.2-63.3%, 10.9-22.8%, 1.9-6.0%, and 0% during the follow-up period. There were significant reductions in peak MV gradient (P=0.042) and left ventricular internal diameter in diastole (LVIDd; P=0.008) post-MVR, as well as LVIDd (P<0.001) and Left Atrial (LA) Volume Index (P=0.019) post-MVr. Octogenarians exhibit positive left atrial and left ventricular remodeling following MVR. Perioperative morbidity is low, late survival is reasonable, and long-term morbidity is considerable. Overall, these results add to the growing literature that MV surgery is relatively safe and effective in octogenarians.

Adulthood adiposity affects cardiac structure and function in later life.

Excess adiposity is associated with poorer cardiac function and adverse left ventricular (LV) remodelling. However, its importance over the adult life course on future cardiac structure and systolic and diastolic function is unknown. A total of 1690 participants in the National Survey of Health and Development birth cohort underwent repeated adiposity [body mass index (BMI)/waist-to-hip ratio (WHR)] measurements over adulthood and investigation, including echocardiography at age 60-64 years. The relationship between LV structure [LV mass (LVM), relative wall thickness, and LV internal diameter in diastole (LVIDd)] and function (diastolic: E/e', e', and left atrial volume indexed to body surface area; systolic: ejection fraction, S', and myocardial contraction fraction) was investigated using multivariable linear regression models. Increased BMI from age 20 years onwards was associated with greater LVM and LVIDd independent of confounders. Associations remained independent of current BMI for LVIDd and at age 26, 43, and 53 years for LVM. Increased BMI from 43 years onwards was associated with greater relative wall thickness, but not when BMI at age 60-64 years was accounted for. Increased BMI at age 26, 36, and 53 years and at 20 years onwards was associated with lower ejection fraction and myocardial contraction fraction, respectively, but not independently of BMI at 60-64 years. Higher BMI from 20 years onwards was associated with poorer diastolic function independent of confounders. Associations between BMI and left atrial volume indexed to body surface area persisted from 26 years onwards after adjustment for BMI at 60-64 years. Similar relationships were observed for WHR from age 43 years onwards. Higher adiposity (BMI/WHR) over adulthood is associated with evidence of adverse cardiac structure and function. Some of these associations are independent of adiposity in later life.

Cardiac Reverse Remodeling Mediated by HeartMate 3 Left Ventricular Assist Device: Comparison to Older Generation Devices.

Currently, the fully magnetically levitated left ventricular assist device (LVAD) HeartMate 3 (HM3) is the only commercially available device for advanced heart failure (HF) patients. However, the left ventricular (LV) functional and structural changes following mechanical unloading and circulatory support (MCS) with the HM3 have not been investigated. We compared the reverse remodeling induced by the HM3 to older generation continuous-flow LVADs. Chronic HF patients (n = 405) undergoing MCS with HeartWare Ventricular Assist Device (HVAD, n = 115), HM3 (n = 186), and HeartMate II (HM2, n = 104) at four programs were included. Echocardiograms were obtained preimplant and at 1, 3, 6, and 12 months following LVAD implantation. There were no differences in the postimplant serial LV ejection fraction (LVEF) between the devices. The postimplant LV internal diastolic diameter (LVIDd) was significantly lower for HM2 at 3 and 6 months compared with HVAD and HM3. The proportion of patients achieving "cardiac reverse remodeling responder" status (defined as LVEF improvement to ≥40% and LVIDD ≤5.9 cm) was 11.9%, and was similar between devices. HeartMate 3 appears to result in similar cardiac reverse remodeling as older generation CF-LVADs, suggesting that the fully magnetically levitated device technology could provide an effective platform to further study and promote cardiac reverse remodeling.

Cardiac screening in pediatric patients with neurofibromatosis type 1: similarities with Noonan syndrome?

Both Neurofibromatosis type 1 (NF1) and Noonan syndrome (NS) are RASopathies. Characteristic cardiac phenotypes of NS, including specific electrocardiographic changes, pulmonary valve stenosis and hypertrophic cardiomyopathy have not been completely studied in NF1. Purpose: The aims of this study were to assess: (1) similarities in the prevalence and types of ECG and conventional echocardiographic findings described in NS in asymptomatic patients with NF1, and (2) the presence of discrete myocardial dysfunction in NF1 patients using myocardial strain imaging. Methods: Fifty-eight patients with NF1 (ages 0–18 years), and thirty-one age-matched healthy controls underwent cardiac assessment including blood pressure measurements, a 12-lead ECG, and detailed echocardiography. Quantification of cardiac chamber size, mass and function were measured using conventional echocardiography. Myocardial strain parameters were assessed using 2-Dimensional (2D) Speckle tracking echocardiography. Results: Asymptomatic patients with NF1 had normal electrocardiograms, none with the typical ECG patterns described in NS. However, patients with NF1 showed significantly decreased calculated Z scores of the left ventricular internal diameter in diastole and systole, reduced left ventricular mass index and a higher incidence of cardiac abnormal findings, mainly of the mitral valve, in contrast to the frequently described types of cardiac abnormalities in NS. Peak and end systolic global circumferential strain were the only significantly reduced speckle tracking derived myocardial strain parameter. Conclusions: Children with NF1 demonstrated more dissimilarities than similarities in the prevalence and types of ECG and conventional echocardiographic findings described in NS. The role of the abnormal myocardial strain parameter needs to be explored.

Effect of Butorphanol-Medetomidine and Butorphanol-Dexmedetomidine on Echocardiographic Parameters during Propofol Anaesthesia in Dogs.

This study compared the effects of butorphanol-medetomidine and butorphanol-dexmedetomidine combinations on echocardiographic parameters during propofol anaesthesia in dogs. The dogs were randomly divided into two groups. In the butorphanol-medetomidine (BM) group, butorphanol (0.2 mg/kg) and medetomidine (15 μg/kg) were intravenously administered; in the butorphanol-dexmedetomidine (BD) group, butorphanol (0.2 mg/kg) and dexmedetomidine (7.5 μg/kg) was used. Anaesthesia was induced with propofol and maintained with a constant-rate infusion of propofol (0.2 mg/kg/min). The echocardiographic parameters were assessed in conscious dogs (T0). Echocardiography was conducted again at 10 min post premedication (T1), followed by assessments at 30 (T2), 60 (T3), and 90 (T4) mins. The dogs were subjected to diagnostic procedures (radiography, computed tomography) under anaesthesia. A significant reduction in heart rate and cardiac output was noted in both groups at T1. There was no significant difference in the stroke volume between the BM and BD groups. The application of butorphanol-dexmedetomidine caused a significant increase in the left ventricular internal diameter in diastole and the diameter of the left atrium compared to that caused by butorphanol-medetomidine. This study documented that butorphanol-medetomidine and butorphanol-dexmedetomidine combinations caused similar reductions in heart rate and cardiac output in both groups. 'New´ valvular regurgitation occurred following their administration.

CARDIOVASCULAR OUTCOMES IMPROVE IN CHILDREN WITH RENOVASCULAR HYPERTENSION FOLLOWING ENDOVASCULAR AND SURGICAL INTERVENTIONS

Objective: Renovascular hypertension (RVH) is a common cause of hypertension in children. It is caused by renal artery stenosis reducing the blood supply to the renal parenchyma and activating the renin-angiotensin-aldosterone axis, often leading to cardiac remodelling. This is a longitudinal observational study that aims to describe the occurrence of hypertensive changes and their severity and also any improvement in cardiac remodelling after successful endovascular and/or surgical intervention in children with RVH. Design and method: All patients with RVH referred to our centre, who had received at least one endovascular intervention, were included. Data was collected by retrospective database review over a 22-year period. We assessed oscillometric blood pressure as well as eight echocardiographic parameters pre- and post-intervention: intraventricular septal diameter (IVSD), posterior wall diameter (PWD), left ventricular internal diastolic diameter (LVIDD), fractional shortening (FS), Relative Wall Thickness (RWT), Left Ventricular Mass (LVM) and Left Ventricular Ejection Fraction (LVEF). Results: 152 patients met inclusion criteria and had on average two endovascular interventions. Six children presented in frank heart failure. 54.4% achieved normal blood pressure (BP) control after intervention. Average z-scores improved in IVSD, PWD and FS; LVMI and RWT also improved. PWD saw the greatest reduction in mean difference in children with an abnormal (z-score reduction of 0.25, p&lt;0.001) and severely abnormal (z-score reduction of 0.23, p&lt;0.001) z-scores between pre- and post-intervention echocardiograms. 45.9% of children had a reduction in prescribed antihypertensive medications. Conclusions: Our study reports improvement in cardiac outcomes after either endovascular or surgical intervention. This is evidenced on BP control and echocardiogram changes in which almost half achieved normalisation in systolic BP readings and reduction in the number of children with abnormal echocardiographic parameters.

Percutaneous Coronary Intervention as a Non-Surgical Treatment for Ischemic Mitral Regurgitation in Patients with Multi-Vessel Coronary Artery Disease.

BACKGROUND Multi-vessel coronary artery disease (MVD) represents a severe type of coronary artery disease (CAD). Ischemic mitral regurgitation (IMR) is a common mechanical complication in patients with CAD. This study aimed to retrospectively investigate the efficacy of percutaneous coronary intervention (PCI) on moderate/severe IMR in patients with MVD. MATERIAL AND METHODS Clinical data were collected from 15 patients who underwent successful treatment for MVD combined with moderate/severe IMR through the PCI procedure and achieved complete revascularization between January 2014 and December 2022. Cardiac structural and functional parameters were assessed through echocardiographic evaluations. Color flow recordings of MR jets were obtained through an enlarged view of the 4-chamber cut, and the diagnosis of MR was categorized into mild (<4 cm²), moderate (4-8 cm²), and severe (>8 cm²), based on the MR area. RESULTS The common features of the selected cases were advanced age, low body weight, and renal insufficiency. Cardiac echocardiography revealed an augmentation in the left atrial anteroposterior diameter and left ventricular internal diameter at end-systole after PCI, while the left ventricle internal diameter in diastole, left ventricular ejection fraction, and left ventricular fractional shortening were comparable to preoperative values. All patients had moderate/severe MR preoperatively, and MR improved at 1 month (2.73±0.69) and 12 months (2.26±0.58) after PCI. CONCLUSIONS In cases of MVD accompanied by moderate/severe IMR, undergoing PCI can spare certain elderly patients with low body weight and renal insufficiency from high-risk surgery, alleviating the severity of MR without undergoing mitral valve intervention.

Relationship between syringomyelia and myxomatous mitral valve disease in Cavalier King Charles spaniels.

Syringomyelia (SM) and myxomatous mitral valve disease (MMVD) are highly prevalent in Cavalier King Charles spaniels (CKCS). Cardiac status in CKCS with and without SM is currently unknown. To investigate the association between SM and MMVD severity in CKCS and CKCS with SM with and without clinical signs of SM. Fifty-five CKCS: 40 with SM (22 symptomatic and 18 asymptomatic) and 15 without SM. A combined retrospective and prospective study. MRI and echocardiography were used to diagnose SM and MMVD, respectively. The association between SM and MMVD severity (left ventricle internal diameter in diastole normalized to bodyweight [LVIDDN] and left atrium to aortic ratio [LA/Ao]) were tested using multivariable linear regression analysis adjusting for sex and age. Overall, no significant difference in LVIDDN and LA/Ao was found between CKCS with or without SM. However, CKCS with symptomatic SM had significantly smaller LVIDDN (1.45 [1.30-1.50]) (median [IQR]) and LA/Ao (1.20 [1.10-1.28]) compared to CKCS with asymptomatic SM (1.60 [1.50-1.90] and 1.40 [1.20-1.75]) as well as CKCS without SM (0.24 [0.03-0.45] and 0.30 [0.05-0.56]) (all P values <.03). An association between MMVD and SM was not confirmed in this cohort of CKCS, indicating that MMVD and SM do not co-segregate. However, CKCS with symptomatic SM had smaller left ventricle and atrial size compared to CKCS with asymptomatic SM and CKCS without SM.

Fuyu Decoction ameliorates myocardial fibrosis in rat model of heart failure by regulating Nrf2/GPX4-mediated ferroptosis

This study aims to investigate the effect and mechanism of Fuyu Decoction(FYD) in the treatment of myocardial fibrosis in the rat model of heart failure(HF). Sixty Wistar rats were randomized into a modeling group(n=50) and a sham group(n=10). A post-myocardial infarction HF model was established by ligating the left anterior descending coronary artery in rats. The successfully modeled rats were assigned into model, low-dose(2.5 g·kg~(-1)) FYD(FYD-L), high-dose(5.0 g·kg~(-1)) FYD(FYD-H), and FYD+Nrf2 inhibitor(ML385, 30 mg·kg~(-1)) groups(n=10). FYD was administrated by gavage and ML385 by intraperitoneal injection. The rats in the sham and model groups were administrated with equal amounts of normal saline by gavage. After 8 weeks of intervention, the cardiac function indicators were measured, and the myocardial tissue morphology and collagen deposition were observed. The positive expression of collagens Ⅰ and Ⅲ, apoptosis, and oxidative stress were examined, and the levels of Fe~(2+) and reactive oxygen species(ROS) were determined. The protein levels of nuclear factor erythroid 2-related factor 2(Nrf2), solute carrier family 7 member 11(SLC7A11), glutathione peroxidase 4(GPX4), and acyl-coenzyme A synthase long chain family member 4(ACSL4) in the myocardial tissue were determined. Compared with sham group, the model group showed decreased left ventricular ejection fraction(LVEF) and left ventricular fractional shortening(LVFS), increased left ventricular end internal dimension in systole(LVIDs), left ventricular internal diameter in diastole(LVIDd), and myocardial collagen deposition, positive expression of collagens Ⅰ and Ⅲ, elevated apoptosis rate and malondialdehyde(MDA), Fe~(2+), and ROS levels, lowered superoxide dismutase(SOD) and glutathione peroxidase(GSH) levels, down-regulated protein levels of Nrf2, SLC7A11, and GPX4, and up-regulated protein level of ACSL4. Compared with the model group, the above indicators were restored by FYD. Moreover, ML385 reversed the protective effect of FYD on myocardial fibrosis in HF rats. In conclusion, FYD can inhibit ferroptosis by activating the Nrf2/GPX4 pathway, thereby ameliorating myocardial fibrosis in HF rats.

Echocardiographic Evaluation of Infants Born to Mothers with Gestational Diabetes Mellitus: A Cross-sectional Analytical Study

Introduction: Gestational Diabetes Mellitus (GDM) is a chronic and progressive disease characterised by changes in the metabolism of carbohydrates, lipids, and proteins, leading to glucose intolerance. The foetal heart in GDM is affected throughout the gestational period, which may result in hyperplasia and hypertrophy of myocardial cells. Aim: To determine the cardiac function and structural changes in infants of gestational diabetic mothers using Dopplerechocardiographic data. Materials and Methods: A cross-sectional analytical study was conducted on 30 infants of mothers with GDM and 30 infants of non diabetic mothers at the Department of Physiology, R.G. Kar Medical College and Hospital, in collaboration with the Departments of Paediatric Medicine and Cardiology from January 2023 to August 2023. Neonatal screening echocardiography was performed by a cardiologist using a Philips Echocardiograph machine, Model: EPIQ 7C, Software Version: 4.0.2, with a linear convex probe of S8-3 MHz frequency to assess cardiac structure and function using 2D, M mode, and Conventional Doppler. The parameters studied included aortic root diameter (mm), left atrial diameter (mm), Interventricular Septal (IVS) in diastole (mm), left ventricular posterior wall thickness in diastole (mm), left ventricular internal diameter in diastole (mm), left ventricular internal diameter in end systole (mm), left ventricular fractional shortening (%), and left ventricular ejection fraction (%). Statistical analysis was performed using the Statistical Package for Social Sciences (SPSS) version-20.0 with an Independent Student’s t-test. Results: The mean gestational age for the cases was 38.50±2.57 weeks and 39.30±1.97 weeks for controls. The mean maternal age for cases was 25±4.37 years and for controls was 27±5.03 years. The left atrial diameter in cases (12.83±2.14 mm) was significantly smaller than that of the control (14.20±0.55 mm). The left ventricular posterior wall diameter in diastole was significantly increased in cases (4.53±0.50 mm) compared to controls (3.87±0.35 mm). Significant differences were observed in the interventricular septum in diastole {cases: 4.73±0.45 mm, control: 3.97±0.32 mm} and in the left ventricular internal diameter in end systole {cases: 12.30±1.84 mm, control: 13.83±1.02 mm} between cases and controls. Aortic root diameter was increased in 13.3% of cases. The percentage of left ventricular fractional shortening (cases: 35.47±3.74 %, Control: 38.53±2.43 %), Left Ventricular Ejection fraction (cases: 67.63±4.52 %, control: 72.17±4.89 %) were significantly decreased in cases compared to control. Conclusion: The present study demonstrated the development of ventricular hypertrophy and compromised myocardial contractility in infants of diabetic mothers.

Left ventricular strain and myocardial work in short-term peritoneal dialysis patients

Background Initiation of dialysis encompasses new cardiovascular challenges on patients with end-stage renal disease (ESRD). This study used two-dimensional speckle-tracking echocardiography (2D-STE) to investigate the change of left ventricular (LV) myocardial function undergoing peritoneal dialysis (PD) within 1–3 months. Methods A total of 56 patients with ESRD and 27 healthy controls were enrolled in this prospective study. Mean duration of PD was 44.41 ± 16.44 days. We evaluated LV myocardial function of patients with ESRD in baseline and within 1–3 months after PD by 2D-STE with global longitudinal strains (GLS) and myocardial work (MW). Based on the level of serum phosphate before PD, patients were divided into two groups: the group with normal serum phosphate or hyperphosphatemia. Results Compared with healthy controls, patients with ESRD had impaired GLS (p < .001) and increased global work index (GWI) (p = .034), global constructive work (GCW) (p < .001), global wasted work (GWW) (p < .001), and lower global work efficiency (GWE) (p = .002). After PD therapy, GWI (p = .001), GCW (p < .001), and GWW (p = .023) decreased and closed to healthy subjects (p > .05) and no significant improvement was observed in GLS (p = .387). GLS of basal segments worsened in the hyperphosphatemia group (p = .005) and GWW reduced remarkably in the group with normal serum phosphate after PD treatment (p = .008). The change of left ventricular internal diameter in diastole (LVIDd) was the only parameter influenced GWI in post-dialysis patients (β = 0.324, p = .013). Conclusions Short-term PD treatment improved LV MW in ESRD patients. They benefited more when receiving treatment before the increase of serum phosphorus.

Effect and mechanism of Jiming Powder on myocardial fibrosis in mice with myocardial infarction

Jiming Powder is a traditional ancient prescription with good therapeutic effect in the treatment of heart failure, but its mechanism lacks further exploration. In this study, a mouse model of coronary artery ligation was used to evaluate the effect and mechanism of Jiming Powder on myocardial fibrosis in mice with myocardial infarction. The study constructed a mouse model of heart failure after myocardial infarction using the method of left anterior descending coronary artery ligation. The efficacy of Jiming Powder was evaluated from multiple angles, including ultrasound imaging, hematoxylin-eosin(HE) staining, Masson staining, Sirius Red staining, and serum myocardial enzyme spectrum detection. Western blot analysis was performed to detect key proteins involved in ventricular remodeling, including transforming growth factor-β1(TGF-β1), α-smooth muscle actin(α-SMA), wingless-type MMTV integration site family member 3a(Wnt3a), β-catenin, matrix metallopeptidase 2(MMP2), matrix metallopeptidase 3(MMP3), TIMP metallopeptidase inhibitor 1(TIMP1), and TIMP metallopeptidase inhibitor 2(TIMP2). The results showed that compared with the model group, the high and low-dose Jiming Powder significantly reduced the left ventricular internal diameter in systole(LVID;s) and diastole(LVID;d), increased the left ventricular ejection fraction(LVEF) and left ventricular fractional shortening(LVFS), effectively improved cardiac function in mice after myocardial infarction, and effectively reduced the levels of myocardial injury markers such as creatine kinase(CK), creatine kinase isoenzyme(CK-MB), and lactic dehydrogenase(LDH), thus protecting ischemic myocardium. HE staining showed that Jiming Powder could attenuate myocardial inflammatory cell infiltration after myocardial infarction. Masson and Sirius Red staining demonstrated that Jiming Powder effectively inhibited myocardial fibrosis, reduced the collagen Ⅰ/Ⅲ ratio in myocardial tissues, and improved collagen remodeling after myocardial infarction. Western blot results showed that Jiming Powder reduced the expression of TGF-β1, α-SMA, Wnt3a, and β-catenin, decreased the levels of MMP2, MMP3, and TIMP2, and increased the level of TIMP1, suggesting its role in inhibiting cardiac fibroblast transformation, reducing extracellular matrix metabolism in myocardial cells, and lowering collagen Ⅰ and α-SMA content, thus exerting an anti-myocardial fibrosis effect after myocardial infarction. This study revealed the role of Jiming Powder in improving ventricular remodeling and treating myocardial infarction, laying the foundation for further research on the pharmacological effect of Jiming Powder.

Efficacy and mechanism of Xuefu Zhuyu Decoction on model rats of coronary heart disease with heart blood stasis syndrome based on metabolomics

This study investigated the effects of Xuefu Zhuyu Decoction on myocardial metabolites in a rat model of coronary heart disease with heart blood stasis syndrome and explored the therapeutic mechanism of blood circulation-promoting and blood stasis-removing therapy. SD rats were randomly divided into a sham operation group, a model group, a Xuefu Zhuyu Decoction group(14.04 g·kg~(-1)), and a trimetazidine group(5.4 mg·kg~(-1)). The sham operation group underwent thread insertion without ligation, while the other groups underwent coronary artery left anterior descending branch ligation to induce a model of coronary heart disease with heart blood stasis syndrome. Three days after modeling, drug intervention was performed, and samples were taken after 14 days of intervention. General conditions were observed, and electrocardiogram and cardiac ultrasound indices were measured. Hematoxylin-eosin(HE) staining and Masson staining were used to observe tissue pathological morphology. The enzyme linked immunosorbent assay(ELISA) was used to measure the levels of triglyceride(TG) and total cholesterol(TC) in the serum. Ultra high performance liquid chromatography-quantitative exactive-mass spectrometry(UHPLC-QE-MS) technology was used to screen differential metabolites in myocardial tissue and conduct metabolic pathway enrichment analysis. The results showed that Xuefu Zhuyu Decoction significantly improved the general condition of the model rats, reduced heart rate and ST segment elevation in the electrocardiogram, increased left ventricular ejection fraction(LVEF) and left ventricular fractional shortening(LVFS), and decreased left ventricular internal diameter in diastole(LVIDd) and left ventricular internal diameter in systole(LVIDs). HE staining and Masson staining showed that Xuefu Zhuyu Decoction effectively alleviated myocardial tissue structural disorders, inflammatory cell infiltration, and collagen fiber deposition in the model rats. ELISA results showed that Xuefu Zhuyu Decoction effectively regulated serum TG and TC levels in the model rats. There were significant differences in the metabolic phenotypes of myocardial samples in each group. Fourteen differential metabolites were identified in the Xuefu Zhuyu Decoction group, involving five metabolic pathways, including arginine and proline metabolism, glycerophospholipid metabolism, aminoacyl-tRNA biosynthesis, ether lipid metabolism, and alanine, aspartate, and glutamate metabolism. Xuefu Zhuyu Decoction improved cardiac function and myocardial structural damage in the rat model of coronary heart disease with heart blood stasis syndrome, and its biological mechanism involved the regulation of lipid metabolism, choline metabolism, amino acid metabolism, energy metabolism, and protein synthesis pathways.

Cardiac Dimensions in Normal Pregnancy: A Prospective Study.

Pregnancy, a unique physiologic state, is associated with several changes in the various body systems. The cardiovascular system is one of the systems affected, with chronic volume overload being one of the characteristic changes experienced during pregnancy. Cardiovascular disease in pregnancy is the leading cause of non-obstetric maternal death worldwide. This study aims to determine and describe the changes in left and right ventricular and atrial sizes in systole and diastole in the course of normal pregnancy. A cohort study was conducted among healthy pregnant women between the age of 18 and 40 who attended the antenatal clinic of Federal Medical Centre (FMC), Yenagoa, Bayelsa State. Fifty women were recruited during the first trimester (T1) of pregnancy and followed up until six weeks postpartum. Ethical approval was obtained from the Research Ethics Committee of Federal Medical Centre, Yenagoa, with approval number FMCY/REC/ECC/2019/JAN/150. Clinical evaluation, hematologic, biochemical, and anthropometric assessments, and two-dimensionalM-mode and Doppler echocardiography were done for the participants in each trimester of pregnancy and at six weeks postpartum. The clinical and echocardiographic parameters were analyzed using Statistical Package for the Social Sciences (SPSS) version 22.0 (IBM Corp., Armonk, NY, USA). The mean trend ofleft ventricular posterior wall thickness in diastole (LVPWd) and left ventricular posterior wall thickness in systole (LVPWs) increased progressively from the first to third trimester (T3) (not statistically significant) but dropped towardinitial values in postpartum to the level that was statistically significant for LVWPd alone when compared to baseline first trimester values. The left atrial diameter in systole (LADs) was largest in the third trimester, and the left atrial volume index (LAVI)and right ventricular basal diameter (RVD1) also showed a similar trend. The left ventricular internal diameter (LVID) in both systole and diastole increased progressively from the first to the third trimesters, but the increase was only statistically significant between the third trimester (T3) and the first trimester (T1). The right atrial diameter (RAD) and right atrial volume (RAV) alsoincreased progressively from the first to the third trimesters, but the increase was only statistically significant between the third trimester (T3) and the first trimester (T1). Changes were noticed in the cardiac chamber sizes during pregnancy. However, this reversed back to levels similar to the first trimester during the postpartum period. To aid in the early detection and treatment of cardiovascular disorders in pregnancy,screening of apparently healthy pregnant women who later developed complaints is advised as cardiovascular changes could be significant during pregnancy.

Cardiotoxicity of BRAF/MEK Inhibitors: A Longitudinal Study Incorporating Contemporary Definitions and Risk Scores

BackgroundRapidly accelerated fibrosarcoma B-type (BRAF) and mitogen-activated extracellular signal-regulated kinase (MEK) inhibitors have revolutionized treatment for patients with BRAF-mutated melanoma. Although left ventricular systolic dysfunction associated with these therapies has been reported in clinical trials, the real-world incidence is poorly defined, as are risk factors for its development. ObjectivesThis study sought to characterize the incidence, time course, and risk factors for cancer therapy–related cardiac dysfunction (CTRCD) in patients with melanoma receiving BRAF and MEK inhibitors. MethodsPatients with melanoma treated with BRAF and MEK inhibitors at a cancer hospital network between June 1, 2017, and June 30, 2020, were included retrospectively. CTRCD was defined as mild, moderate, or severe according to International Cardio-Oncology Society (ICOS) definitions. Baseline cardiotoxicity risk stratification was performed using the Heart Failure Association/ICOS tool. ResultsOf the 63 patients included, 27% developed CTRCD (17% mild and 10% moderate). No patients developed severe CTRCD or symptomatic heart failure. CTRCD occurred most frequently in patients considered to be at “low” and “medium” baseline risk of cardiotoxicity (82%). The baseline left ventricular ejection fraction and global longitudinal strain were not different in patients who developed moderate CTRCD vs those who did not. Left ventricular internal diameters in diastole and systole were larger in patients who developed moderate CTRCD compared with those who did not (left ventricular internal diameter in diastole: 4.9 ± 0.6 cm vs 4.3 ± 0.6 cm; P = 0.023; left ventricular internal diameter in systole: 3.3 ± 0.4 cm vs 2.8 ± 0.5 cm; P = 0.039). ConclusionsBRAF and MEK inhibitor–associated CTRCD is common. The utility of the Heart Failure Association/ICOS risk stratification tool appears limited in this group, and better risk prediction tools are needed. The long-term consequences of CTRCD, particularly mild CTRCD, warrant evaluation in larger prospective studies.

Investigating the effects of thermoneutral housing on skeletal and cardiac muscle function in D2 mdx mice

Since its discovery, the mdx mouse has been the foundation for research on Duchenne muscular dystrophy (DMD) and its potential therapies. Although, nearly all studies using mdx mice as an experimental model have been conducted under “standard” lab conditions using room (22C) instead of thermoneutral (TN, 30C) temperature housing. Room temperature (RT) is a mild cold stress to mice, causing metabolic adaptations that can confound experimental results, limiting their interpretation and translation to humans. This study investigated the effects of housing temperature on whole-body metabolism and skeletal and cardiac muscle function in the mdx mouse. To this end, 20 D2 mdx mice (age 5 weeks, n = 10 per group) were housed at RT and TN for 10 weeks. Metabolic cage analysis demonstrated that TN housed mdx mice displayed significantly decreased VO2 consumption and reduced food intake that was likely due to lowered daily energy expenditure. TN housed mice also had significantly lower respiratory exchange ratio values, indicative of increased fat metabolism. However, there were no differences in body mass or composition (i.e., % lean and fat mass). Treadmill-to-fatigue experiments revealed no differences in exercise performance. Furthermore, ex vivo muscle contractility analysis displayed no differences in extensor digitorum longus or soleus specific force generation between TN and RT housed mice. Analysis of cardiac structure/function demonstrated that TN housed mdx mice exhibited a reduction in cardiac output, which we attributed to diastolic dysfunction. While ejection fraction and fractional shortening were not different among the two groups, TN housing led to a significant reduction in end diastolic volume (EDV) and left ventricle internal diameter (diastole, LVID;d), as well as increased relative wall thickness (diastole, RWT;d) compared to RT housed mice. Though isovolumic relaxation time was prolonged in TN-housed mice, this did not reach statistical significance. Taken together, our results demonstrate that TN housing had minimal effects on skeletal muscle contractility, but did lead to signs of diastolic dysfunction in young mdx mice. Future studies will examine the effects of TN housing in aged mdx mice, when systolic dysfunction occurs, as well as any influence of TN housing on the efficacy of potential muscle wasting therapeutics. Overall, our results support the growing literature that highlights the importance of selecting the appropriate housing temperature when studying metabolism or muscle wasting conditions in mice. NSERC This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Echocardiographic reference intervals and cut-off values to diagnose dilated cardiomyopathy in guinea pigs (Cavia porcellus)

The objective of this study was to establish reference intervals in healthy guinea pigs and to calculate optimal cut-off values for several M-Mode parameters to diagnose dilated cardiomyopathy (DCM) phenotype. This prospective study included 146 guinea pigs. The apparently healthy group included 92 animals and was used to create reference intervals for left ventricular internal diameter in diastole (LVIDd), left ventricular internal diameter in systole (LVIDS), E-point-to-septal separation (EPSS), diastolic wall thickness and left atrium and aorta. Allometric scaling was used to normalize LVIDd(-n) and LVIDs(-n) to body weight with a scaling exponent (BWexp). The DCM phenotype group included 54 subjects and was used to calculate optimal cut-off values of several M-mode parameters. Guinea pigs with DCM phenotype had significantly larger measurements of LVIDd, LVIDs and EPSS, as well as lower FS and wall thicknesses compared to apparently healthy guinea pigs. Allometric scaling exponents to normalize LVIDd and LVIDs to BW (g) were 0.336 and 0.346, respectively. The highest area under the curve (AUC) to diagnose DCM were found for LVIDs-n (cut-off value >0.74 mm, AUC 0.996), FS (cut-off value <29%, AUC 0.995), LVIDd-n (cut-off value >1.07 mm, AUC 0.980) and EPSS (cut-off value >1.4 mm, AUC 0.944). M-mode and 2D reference intervals for guinea pigs are presented, including lower and upper limits. Diagnosis of DCM phenotype in guinea pigs can be established using parameters known to be useful in other species, namely LVIDs, LVIDs-n, FS, LVIDd, LVIDd-n and EPSS.