Systolic Volume Research Articles

Intradialytic non-invasive hemodynamic monitoring: usefulness of cardiac preload values in predicting hemodynamic instability

IntroductionAdequate control of patient blood volume in hemodialysis (HD) is essential as a modifiable risk factor for morbidity and mortality. In this study, we propose continuous non-invasive hemodynamic monitoring using bioreactance (Starling SV.Baxter) and real-time characterization of cardiac preload data to aid in the accurate assessment of volume status and improvement of tolerance in HD. MethodologyObservational and prospective study on the relationship between cardiac preload data and intradialytic hemodynamic instability. Forty-six stable HD patients were recruited. Clinical, analytical, and dialysis data were collected from all participants. The protocol included bioimpedance (BIVA), pre- and post-dialysis echocardiography and tissue Doppler, and monitoring of hemodynamic parameters during the session. ResultsAccording to the Fall20 definition, 24 patients (51.19%) experienced intradialytic hypotension (IDH). We found no relationship between IDH and analytical, echocardiographic, BIVA parameters, or relative blood volume measurement (BVM) values. Regarding hemodynamic monitoring, indexed systolic volume (ISV) was lower in patients with IDH (38.2 ± 0.9 vs. 39.2 ± 1.9; p < 0.001). Indexed systolic volume variation (ISVV) and heart rate (HR) were higher in the IDH group (14.1 ± 0.7 vs. 13.5 ± 0.7; p < 0.0001), (70.01 ± 2.1 vs. 68.97 ± 1.1; p < 0.0001), respectively. Indexed cardiac output (ICO) and indexed peripheral resistances (IPR) were also lower in the IDH group (2.62 ± 0.09 vs. 2.65 ± 0.13; p < 0.05) and (3201 ± 325 vs. 3432 ± 231; p < 0.05), respectively. Patients who started the session with lower preload (ΔSV after infusion of 250 cc ≥ 10%) more frequently developed IDH (p < 0.001). ConclusionsNon-invasive hemodynamic monitoring and preload data may constitute a valid tool in managing the volume status of HD patients and preventing IDH.

Features of indicators of macrohemodynamics and systemic inflammation in patients with community-acquired pneumonia combined with gastroesophageal reflux disease

Relevance. The clinical course, treatment approaches, and outcomes of community-acquired pneumonia (CAP) often depend on microcirculatory disorders. The significant prevalence of gastroesophageal reflux disease (GERD) in the population determines the frequency of CAP. Study of the pathogenetic basis of the combined course of CAP in individuals with GERD, incl. microcirculation systems, can target correction paths and increase the effectiveness of therapy.Objective. To identify indicators of systemic inflammation and macrohemodynamics in patients with CAP combined with GERD.Material and methods. A total of 123 patients were under observation, incl. with mild CAP without signs of GERD (group I) — 38, with CAP and GERD — 49 (group 2), and 36 patients with GERD without CAP — group 3. In all patients with CAP, along with traditional studies, the concentrations of C-reactive protein (CRP) and brain natriuretic peptide (BNP) were determined in the blood, and echocardioscopy (EchoCS) was performed to determine the end systolic (ES) and diastolic (ED) volumes of the left ventricle (LV) and right ventricles (RV), blood flow velocity at the level of the pulmonary artery (Vmax PA), pressure gradients ΔPmax at the level of the tricuspid valve (TV), PA, and LV isovolumic relaxation time (IVRT). Control values for indicators were obtained from 34 practically healthy donors.Results. In all patients with CAP, at the beginning of therapy, intoxication and respiratory syndromes were observed, and pneumonia was diagnosed on an X-ray. Patients in groups II and III had characteristic symptoms of GERD. Blood tests revealed leukocytosis in all patients with CAP. The initial CRP concentration in group 1 was 5.2, group 2 — 7.7, group 3 — 1.2 times higher than normal. The initial concentration of BNP in all groups did not differ from the control. By discharge, CRP levels in all patients had decreased: however, in group II, they remained higher than in healthy people (2.6 times (p &lt; 0.05) and higher than in group I, 1.3 times (p &lt; 0.05). Before discharge, the BNP level in group II increased by 1.2 times compared with baseline in group I, in healthy individuals, and in group III. When analyzing the EchoCS indicators in group II patients, a significant increase in the initial indicators of LV EDV and LV ESV and decrease in EF and IVRT were observed. After treatment, no significant dynamics of volume and velocity parameters were observed in patients in group II; in patients in group I, pressure gradients at the TC and PA levels remained slightly reduced.Conclusions. An increase in CRP levels in patients with GERD characterizes low-intensity inflammation, which potentiates systemic inflammation in patients with CAP combined with GERD and is accompanied by an increase in BNP.

Abstract 4135531: The Ubiquitin-Specific Protease 30 Inhibitor, MTX652, Attenuates Cardiac Dysfunction And Remodelling In a Murine Model Of Transverse Aortic Constriction

Introduction: Mitochondrial abnormalities are a characteristic of heart failure leading to energy deprivation and disease worsening. The mitochondrial deubiquitinating enzyme USP30, removes ubiquitin and represses PINK1/PARKIN-mediated mitophagy leading to accumulation of dysfunctional mitochondria. In this study we investigated the role of MTX652, a clinical stage USP30 inhibitor, in a mouse model of cardiac hypertrophy using transverse aortic constriction (TAC). Hypothesis: Inhibition of USP30 will promote mitophagy resulting in clearance of dysfunctional mitochondria and improved cellular health leading to cardioprotective effects. Aims: To determine if MTX652 can protect from TAC induced cardiac hypertrophy and remodelling. Methods: Male C57BL/6 mice, 8 weeks old, were subjected to sham surgeries or TAC using a 26G needle to induce cardiac pressure overload. MTX652 (1.5 or 5 mg/kg, n =12-13) or vehicle ( n =11) was administered orally, twice daily, starting 2 days post-surgery. Captopril (30 mg/kg/d, n =13) was also included as a positive control. After 4 weeks, echocardiography assessed left ventricle (LV) function and morphology. Cell based assays assessed MTX652 target engagement and TOM20 ubiquitination in vitro. Results: LV hypertrophy and wall thickening was observed in TAC animals. Treatment with MTX652 decreased systolic LV volume (1.5 mg/kg p&lt;0.05 and 5 mg/kg p&lt;0.01) and diameter (1.5 mg/kg p&lt;0.01 and 5 mg/kg p&lt;0.05,) demonstrating comparable effects to Captopril. A reduction in anterior wall thickness in diastole was also observed with MTX652 (5 mg/kg, p&lt;0.01). Cardiac dysfunction was also evident in TAC animals with MTX652 showing improvements in both ejection fraction (1.5 mg/kg and 5 mg/kg, p&lt;0.0001) and fractional shortening (1.5 mg/kg and 5 mg/kg, p&lt;0.0001). Cellular target engagement for MTX652 was confirmed in HeLa-YFP-Parkin cells with an EC 50 of 2.7 nM ( n =2). Furthermore, the USP30 substrate TOM20 was ubiquitinated following MTX652 treatment in vitro (EC 50 =6.1 nM, n =4) providing evidence of mitophagy activation, a finding also confirmed in mouse heart tissue (MTX652, 5mg/kg). Conclusions: The USP30 inhibitor, MTX652 significantly protected mice from TAC induced cardiac hypertrophy and LV dysfunction. Furthermore, MTX652 potentiates ubiquitylation of TOM20 as a mechanism to promote mitophagy. These data suggest our clinical stage molecule could provide a novel therapeutic approach for the treatment of cardiac hypertrophy and heart failure.

Abstract 4138716: A novel Urocortin-2 analog COR-1167 corrects cardiac and renal dysfunction on top of Empagliflozin in a rat model of acute decompensated heart failure

Introduction: Urocortin-2 (UCN-2) is a peptide belonging to the corticotropin-releasing factor family that has cardiovascular, renal, metabolic and anti-inflammatory actions and improves cardiac function in human heart failure (HF) and cardiorenal dysfunction in chronic HF models. However, UCN-2 has a short half-life and intravenous delivery limits its therapeutic use. COR-1167 was discovered as a stable UCN-2 analog with qd pharmacological effects when injected subcutaneously. Hypothesis: Whether COR-1167 exerts chronic cardiorenal protection in Acute Decompensated HF (ADHF) is unknown, and in particular on background of SGLT2 inhibition, therefore both treatments were tested in a rat model of ADHF. Methods: Rats had coronary artery ligation to induce MI and a reduced ejection fraction phenotype. Three months later, rats were treated with vehicle or Empagliflozin (Empa) at 10 mg/kg/day PO. One month after starting Empa, two acute decompensation events were induced by administrating NaCl solution (1.8 g/kg, PO) on Day 0 and Day 14. Empa treated ADHF rats received vehicle or COR-1167 (3 µg/kg/day) by SC injections starting at 12 hours after the first decompensation and all treatments continued for 14 days. The groups were ADHF, ADHF + Empa and ADHF + Empa + COR-1167 (n=7-10/group). Left ventricular (LV) hemodynamics (cardiac catheters), cardiac output (echocardiography) and LV tissue perfusion (magnetic resonance imaging), cardiac mitochondrial coupling and ATP production (Seahorse) were measured 1 day after the second decompensation, while urine volume (uVol) and urine Na + excretion (uNa + ) collected from metabolic cages were analyzed 7 days after the first decompensation. Results: Compared to ADHF control rats, Empa treatment had no effect on systolic blood pressure (SBP), cardiac output (CO), LV end systolic pressure volume relationship (LVESPVR), LV end diastolic pressure volume relationship (LVEDPR), mitochondrial coupling and ATP production, but it increased myocardial perfusion, uVol and uNa + excretion. Compared to ADHF + Empa rats, COR-1167 treatment increased SBP, CO, LVESPVR, myocardial perfusion, mitochondrial coupling and ATP production, uVol, uNa + , while decreasing LVEDPVR. Conclusion: In the setting of ADHF, significant cardiorenal benefits and decongestion occurred when COR-1167 was administered on top of an SGLT2 inhibitor.

Abstract 4125026: Effect Of Pressure-Controlled Intermittent Coronary Sinus Occlusion On Echocardiographic Features In Patients With STEMI: A Systematic Review And Meta-Analysis With Trial Squential Analysis

Introduction: Primary percutaneous coronary intervention (pPCI) is the treatment of choice for patients with ST-segment elevation myocardial infarction (STEMI). Nevertheless, pPCI is still associated with poorer outcomes particularly left ventricular dysfunction. Pressure-controlled intermittent coronary sinus occlusion (PiCSO) is a novel therapeutic approach proposed to improve myocardial perfusion and its function in patients with STEMI. Therefore, we performed this meta-analysis to evaluate the effects of PiCSO on left ventricular function in STEMI patients. Methods: We performed a comprehensive search on PubMed, Scopus, and Web of Science. Our primary endpoints were left ventricular ejection fraction (LVEF%), left ventricular end diastolic volume (LVEDV), and left ventricular end systolic volume (LVESV). The secondary endpoint was infarct size. We performed Trial Squential Analysis (TSA), and we pooled our continuous data as mean difference (MD) and 95% confidence interval (CI) in the fixed effects model. Results: A total of four studies, with 335 patients, were included in the analysis. Our pooled analysis showed that PiCSO significantly increased LVEF% compared to pPCI (MD = 3.52, 95% CI [1.05, 6.00], P= 0.005). However, there was no significant difference between the two groups in terms of LVESV and LVEDV (MD = -1.1, 95% CI [-9.28, 7.08], P= 0.79; MD = -1.69, 95% CI [-9.14, 5.76], P= 0.66, respectively). With regard to infarct size, a significant reduction was observed in PiCSO group compared to pPCI (MD = -4.26, 95% CI [-7.39, -1.14], P= 0.007). The TSA curve crossed the conventional boundary for statistical significance, indicating that the available evidence reach the predetermined threshold. Conclusions: Our meta-analysis revealed that PiCSO could mitigate left ventricular dysfunction in STEMI patients by improving LVEF% and reducing infarct size. Nevertheless, PiCSO failed to show a positive impact on LVESV and LVEDV. Further large-scale studies are warranted to draw a definitive conclusion.

Abstract 4147633: Structural and Electrophysiological Cardiac Changes in Children with Osteogenesis Imperfecta (OI)

Introduction: Osteogenesis imperfecta (OI) is an inherited type 1 collagen disorder leading to bone fragility and increased fractures. Cardiovascular disease is the leading cause of death of adults with OI, but studies on cardiac changes from this collagen defect in children are sparse. We aim to fill this gap by assessing changes in EKG and echocardiogram (ECHO) variables in children with OI. Hypothesis: Children with OI will exhibit arrhythmogenic EKG changes and/or ECHO abnormalities which will precede changes that are documented in adults. Methods: 53 children with OI receiving care at Children’s Mercy-Kansas City were identified via ICD-10 codes. 64 with Duchenne Muscular Dystrophy (DMD, expected cardiac abnormalities) and 55 with non-accidental trauma (NAT, no expected cardiac abnormalities) served as controls. We specifically compared the most recent EKG and ECHO metrics extracted from medical charts by Kruskal-Wallis testing. Results: EKG: Children with OI differed from both NAT and DMD. OI had shorter median PR intervals (p&lt;0.001) plus longer median QRS (p&lt;0.001) and QTc intervals (p=0.002) than NAT. DMD had the shortest PR and longest QRS and QTc (see Table). Echo: The three groups showed no difference in systolic/diastolic BP or LV thickness. However, OI differed from NAT and/or DMD in other metrics. OI had higher end diastolic volume (p&lt;0.001), end systolic volume (p&lt;0.001) and stroke volume (p&lt;0.05) than NAT, but lower values than the DMD group. Similarly, OI children had higher LV mass and LV internal diastolic and systolic diameters than NAT, but lower than DMD (p&lt;0.001). OI LVOT diameter and Aortic root diameter were lower than NAT, but not as low as DMD (p&lt;0.05 and p&lt;0.001, respectively). Conclusion: Children with OI exhibit EKG and ECHO abnormalities that are similar to but less severe than for DMD, a group in which cardiovascular abnormalities are well documented. These abnormalities may be predictive of arrythmia/sudden cardiac death and/or functional decline in heart function. Our data suggest that OI children could benefit from ongoing routine cardiology studies along with orthopedic/metabolic management. Future studies would assess effects of age and OI treatments on cardiac abnormalities.

Systems Pharmacology to Explore the Potential Mechanism of Ginseng Against Heart Failure.

The aim of this study is to elucidate the pharmacological mechanism underlying the effects of Ginseng Radix et Rhizoma (ginseng) in heart failure (HF), providing a theoretical foundation for its clinical application. The potential mechanism of ginseng in the context of HF was investigated using systems pharmacology that combined network pharmacology, Gene Expression Omnibus (GEO) analysis, molecular docking, and experimental verification. Network pharmacology was employed to identify drug-disease targets. Core gene targets were subsequently subjected to enrichment analysis by integrating network pharmacology with GEO. Molecular docking was utilized to predict the binding affinities between identified targets and ginseng compounds. Furthermore, the therapeutic efficacy of ginseng was validated in an isoproterenol (ISO)-induced rat model of HF. The modulation of key signaling pathways by ginseng was confirmed through Western blot analysis. A total of 154 potential targets of ginseng in the treatment of HF were identified through network pharmacology analysis. The analysis of GSE71613 revealed that the PI3K-Akt pathway, reactive oxygen species, oxidative phosphorylation, MAPK signaling, and Ras signaling pathways are predominantly associated with patients with HF. By integrating the findings from network pharmacology and GEO analysis, ginsenoside Rg1 and ginsenoside Rb3 were identified as the potential components in ginseng, while FN1 and PRKAA2 were recognized as key targets involved in the PI3K-AKT and AMPK pathways, respectively. Molecular docking analysis revealed a strong affinity between the potential components and the identified core targets. In vivo experiments indicated that the extract of ginseng (EPG) significantly ameliorated ISO-induced cardiac dysfunction by improving cardiac parameters such as cardiac left ventricular internal systolic diameter, left ventricular end-diastolic volume, left ventricular end systolic volume, and left ventricular ejection fraction, while also reducing malondialdehyde production. In addition, EPG was found to enhance superoxide dismutase activity and ATP levels, while concurrently reducing the levels of interleukin (IL)-1β, IL-6, and TNF-α. The extract also reduced myocardial oxygen consumption, inflammatory cell infiltration, and the number of damaged myocardial fibers. Moreover, EPG was observed to upregulate the expression of p-PI3K, p-AKT, p-AMPK, and Bcl-2, while downregulating the expression of p-NFκB, TGF-β, and Bax. The therapeutic effects of ginseng on HF are primarily mediated through the PI3K-Akt and AMPK pathways. Ginsenoside Rg1 and ginsenoside Rb3 have been identified as potential therapeutic agents for HF.

Topological recursion for hyperbolic string field theory

We derive an analog of Mirzakhani’s recursion relation for hyperbolic string vertices and investigate its implications for closed string field theory. Central to our construction are systolic volumes: the Weil-Petersson volumes of regions in moduli spaces of Riemann surfaces whose elements have systoles L ≥ 0. These volumes can be shown to satisfy a recursion relation through a modification of Mirzakhani’s recursion as long as L ≤ 2 sinh−1 1. Applying the pants decomposition of Riemann surfaces to off-shell string amplitudes, we promote this recursion to hyperbolic string field theory and demonstrate the higher order vertices are determined by the cubic vertex iteratively for any background. Such structure implies the solutions of closed string field theory obey a quadratic integral equation. We illustrate the utility of our approach in an example of a stubbed scalar theory.

Visual assessment of cerebrospinal fluid flow dynamics using 3D T2-weighted SPACE sequence-based classification system.

Flow-related signal void artifacts can be visualized on the T2-weighted (T2W) three-dimensional sampling perfection with application-optimized contrast (3D-SPACE) sequence. Flow void artifacts in the cerebral aqueduct and the fourth ventricle can provide information about cerebrospinal fluid (CSF) flow dynamics. In this study, we aimed to test the performance of the T2W 3D-SPACE sequence in assessing the CSF flow in the aqueduct and/or fourth ventricle. A total of 137 patients (age range = 3-89 years) who underwent CSF flow study were included. The amount of signal loss on T2W 3D-SPACE due to flow in the aqueduct and fourth ventricle was assessed and graded using a 4-point scale of 0 (absence of flow void) to 3 (signal void filling the aqueduct and entire fourth ventricle). A correlation was then sought between the quantitative values obtained by phase-contrast magnetic resonance imaging (PC-MRI) and the amount of signal void in the 3D-SPACE sequence. At the aqueduct level, there was a statistically significant difference in the forward flow velocity and the flow volume among different grades (all P < 0.001). In the grade 3 group, CSF peak systolic flow velocity and mean flow volume were found to be significantly higher than in the other grades (P < 0.001). The mean aqueduct area in the grade 0 group was found to be significantly different from that in the other classes (P < 0.001). The amount of signal loss in the fourth ventricle observed on T2W 3D-SPACE is correlated with the peak systolic velocity and flow volume measured quantitatively in PC-MRI.

Association of Objectively Measured Sedentary Behavior With Arterial Stiffness: Findings From the Nijmegen Exercise Study.

Sedentary behavior (SB) may affect arterial stiffness, preceding the development of cardiovascular disease. We investigated the association of objectively measured SB with arterial stiffness. We also investigated factors that affected this association. We recruited adult volunteers and measured SB with thigh-worn accelerometery for 24 hrs/day for eight consecutive days. Central (carotid-femoral pulse wave velocity, cfPWV, gold standard) and local carotid arterial stiffness (stiffness index Beta and pressure-strain elasticity EP) were measured with ultrasound. Linear regression was used and adjusted for demographics, cardiometabolic factors, and moderate-to-vigorous physical activity (MVPA) volume. Effect modification was studied with interaction terms. Participants (N = 664, 64 (standard deviation: 11, range: 23-89) years, 397 (59.8%) male) demonstrated 9.1 (1.6) hrs/day of SB, and arterial stiffness was 8.6 (3.0) m/s for cfPWV, 6.4 (2.9) for Beta, and 87 (43) kPa for EP. SB was not associated with cfPWV (β = 0.04 95% CI (-0.11, 0.18), p = 0.60). The association of SB with local arterial stiffness was modified by systolic blood pressure (SBP) and MVPA volume. Stratified analyses revealed positive associations of SB with Beta (β = 0.29 (0.05, 0.53), p = 0.016) and EP (β = 4.83 (1.39, 8.27), p = 0.006) in participants with SBP > 134 mmHg or > 103 min/day of MVPA (β = 0.23 (0.03, 0.42), p = 0.024 and β = 3.55 (0.82, 6.29), p = 0.011, respectively). We found no association of objectively measured SB with central arterial stiffness. However, SB was positively associated with local carotid stiffness in participants with higher SBP or MVPA levels. In certain subgroups, SB may affect carotid arterial stiffening, reinforcing the relation between SB and cardiovascular disease.

Tirzepatide Reduces LV Mass and Paracardiac Adipose Tissue in Obesity-Related Heart Failure: SUMMIT CMR Substudy.

Obesity is a known risk factor for heart failure with preserved ejection fraction (HFpEF) and is considered a distinct phenotype with more concentric remodeling. Epicardial adipose tissue (EAT) is also increased in obesity-related HFpEF and is associated with adverse events. The Cardiac Magnetic Resonance (CMR) Substudy of the SUMMIT trial was aimed to examine the effects of tirzepatide on cardiac structure and function with the underlying hypothesis that it would reduce left ventricular (LV) mass and EAT in obesity-related HFpEF. One hundred seventy-five patients with obesity-related HFpEF from the parent study of tirzepatide (2.5mg SQ weekly, increasing to a maximum of 15mg weekly) or matching placebo underwent CMR at baseline, which consisted of multiplanar cine imaging. One hundred six patients completed the CMR and had adequate image quality for analysis of LV and LA structure and function and paracardiac (epicardial plus pericardial) adipose tissue at both baseline and 52 weeks. The prespecified primary endpoint of this substudy was between-group changes in LV mass. LV mass decreased by 11 g (95% C.I. -19 to -4) in the treated group (n = 50) when corrected for placebo (n =56) (p=0.004). Paracardiac adipose tissue decreased in the treated group by 45 ml (95% C.I. -69 to -22) when corrected for placebo (p<0.001). The change in LV mass in the treated group correlated with changes in body weight (p<0.02) and, tended to correlate with changes in waist circumference and blood pressure (p=0.06 for both). The LV mass change also correlated with changes in LV end diastolic volume and LA end diastolic and end systolic volumes (p<0.03 for all). The CMR substudy of the SUMMIT trial demonstrated that tirzepatide therapy in obesity-related HFpEF led to reduced LV mass and paracardiac adipose tissue as compared to placebo and the change in LV mass paralleled weight loss. These physiologic changes may contribute to the reduction in heart failure events seen in the main SUMMIT trial.

Echocardiographic associates of impaired sleep quality in patients with anxiety and depression

Abstract Objective Sleep health, mental health and cardiovascular health are multidimensional constructs that are strongly associated with each other. Anxiety and depression are the most common psychiatric diseases in the community and frequently comorbid in routine clinical practice. This study sought to investigate whether there is an association between sleep quality and echocardiographic parameters in patients with anxiety and/or depression. Methods The clinical and instrumental find­ings of consecutive patients diagnosed with either of anxiety disorders and/or depressive disorders and underwent cardiac examination in our tertiary center on the same day were retrospectively reviewed. The diagnosis was made by a psychiatrist according to the criteria listed in the fifth edition of The Diagnostic and Statistical Manual of Mental Disorders. Afterwards, Hospital Anxiety and Depression Scale (HADS) and Pittsburgh Sleep Quality Index (PSQI) were applied to patients to assess symptom severity and sleep quality, respectively. Subsequent to psychiatric examination, the patients underwent echocardiographic examination that includes two-dimensional conventional echocardiography, tissue doppler imaging (TDI) echocardiography, atrial conduction times, and left atrium (LA) volumes and functions. Results The final study population consisted of 167 patients and divided into two groups according to their PSQI score: PSQI&amp;lt;5 (normal sleep quality) (n=32) and PSQI≥5 (impaired sleep quality) (n=135). Aortic diameter, left ventricular (LV) end-systolic diameter, LV end-diastolic and -systolic volume, LV stroke volume and LV stroke volume index, LV outflow tract velocity–time integral (LVOT-VTI), and LA conduit volume calculations were significantly lower in patients with impaired sleep quality compared to patients with normal sleep quality. The other echocardiographic parameters including LV systolic functions, doppler and TDI echocardiography indices, atrial conduction times, atrial mechanical functions including LA function index (LAFI) were similar among groups. Correlation analysis yielded a negative, weak but statistically significant correlation between LAFI and PSQI score (r=-0.17, p=.030) (Figure 1A). Left intra-AEMD positively and significantly correlated with PSQI score at a weak level (r=0.16, p=.043) (Figure 1B). Aortic diameter, LV stroke volume index, LVOT-VTI and conduit volume were determined as echocardiographic parameters significantly associated with impaired sleep quality in univariate analysis. Among these parameters, only conduit volume remained as significant and independent associate of impaired sleep quality in multivariate logistic regression analysis (Odds ratio:0.91, 95% Confidence interval:0.85-0.98, p=.018) (Table 1). Conclusion There is an independent association between LA conduit volume and impaired sleep quality in patients suffering from anxiety and/or depressive disorders.Figure 1Table 1

Prognostic value of multiparametric cardiac magnetic resonance after revascularized STEMI

Abstract Despite early revascularization of STEMI through angioplasty, the prognosis following STEMI remains poor for a non-negligible percentage of patients (1). In this setting, multiple imaging parameters have demonstrated their prognostic value. The aim of the present study is to evaluate which of these parameters are the most potent predictors of events following revascularized STEMI. Methods A prospective observational study was conducted, including a cohort of revascularized STEMI patients and who underwent cardiac MRI during the first week. The protocol included cardiac functional analysis and with b-SSFP sequences for evaluation of volumes, mass, ejection fraction and also circumferential and radial strain with feature tracking. STIR sequences were used to assess edema and salvaged myocardium, IR-FGE sequences were employed for evaluation of necrosis size and microvascular obstruction. Intra-infarct hemorrhage assessment was performed using T2* mapping sequences as previosly described (2,3,4) . A semi-automatic analysis was conducted, considering as microvascular obstruction segments with hypointensity in the infarct core and as segments with hemorrhage those with a T2* less than 20 ms. The association of imaging parameters with cardiovascular events in the first year following STEMI was studied using ROC curves. Variables with significant association were analyzed using a multivariate logistic regression model. Results Ninety-four patients with a mean age of 63 (SD 13) years were included. Nine of them had cardiovascular events in the first year and two of them died. The relative extent of necrosis and microvascular obstruction, minimal radial strain, left ventricular ejection fraction (LVEF) and indexed left ventricular end- systolic volume (ILVESV) showed significant association with cardiovascular events after STEMI. Variables with significant association were entered into a multivariate predictive model, revealing that the extent of microvascular obstruction (OR: 1.9, p=0.02) and the left ventricular end-systolic volume (OR: 1.04, p&amp;lt;0.01) are the only independent predictors of cardiovascular events following STEMI. Conclusion Although multiple imaging parameters have shown prognostic value after STEMI, the ILVESV and the extent of microvascular obstruction are the only independent predictors of events following STEMI.Multiparametric cardiac MR in STEMIAREA UNDER ROC CURVE OF CMR PARAMETERS

Deep learning enables the fully automated quantification of high-resolution cardiac CT images: human in loop for model development

Abstract Introduction Cardiac computed tomography (CCT) images provide vast spatial and temporal information. Segmentation of the structure of interest is necessary to provide quantitative information. However, manual segmentation of cardiac substructures is highly time-consuming. Objective This study aims to develop a robust deep-learning segmentation model for cardiac substructure segmentation in 3D CCT images. Method We initially developed a 3D U-Net architecture, incorporating extensive augmentation, for the segmentation of the Left Ventricle Myocardium (LVM), the blood cavities of the Left and Right Ventricles (LV, RV), and the Left and Right Atria (LA, RA). This model utilized CT images from 20 patients who had available manual segmentation. Subsequently, we applied this initial model to datasets from two centers, including different generations of scanners. We then visually inspected the segmentation, selected the highest-quality segmentations, and modify it if necessary, and excluded the low-quality data. We continued fine-tuning the model with the new dataset until we reached a count of 456 patients. As there were multiple images from one patient during this model's development, we generated datasets to develop a new model using the entire new dataset to avoid any data leakage in the reported metrics. The model was developed using data from Center 1 (5-fold cross-validation) and then evaluated on an external test set from Center 2 (126 patients) and also 4D images from Center 1. Various metrics were calculated to assess the model's performance. Results In the internal test set, utilizing 5-fold CV, the model demonstrated high segmentation accuracy, achieving an overall Dice coefficient of 0.98, with individual scores of 0.96 for LVM, 0.98 for LV, 0.98 for RV, 0.99 for RA, and 0.98 for LA. We assessed the automatic quantification capability of the segmentation model from 256 patients, resulting in an R2 value greater than 0.92 for both LV end-diastolic and systolic volumes. In contrast, the model maintained robust performance on the external dataset, achieving an overall Dice coefficient of 0.96, with individual scores of 0.95 for LVM, 0.98 for LV, 0.97 for RV, 0.98 for RA, and 0.94 for LA. Conclusion We provided a large cohort of ground truth segmentations for different cardiac CT substructures using a human-in-the-loop strategy. Subsequently, we developed a deep learning model for highly accurate automated segmentation of these substructures. This model allows for fast and fully automatic segmentation and quantification of 3D and 4D cardiac CT images, from which various quantitative metrics can be extracted from different cardiac substructures.

Cardiac remodeling in rheumatoid arthritis: assessing the influence of anti-CCP and rheumatoid factor

Abstract Background Anti-cyclic citrullinated peptide (anti-CCP) antibodies and rheumatoid factor (RF), markers of Rheumatoid Arthritis (RA) activity, are associated with adverse cardiovascular outcomes, suggesting a potential link between RA and cardiac remodeling. Purpose Our study aimed to explore the correlation between antibody levels (anti-CCP and RF) and left ventricular (LV) remodeling in RA patients without known heart disease. Additionally, it sought to identify other disease-related factors that correlate with LV remodeling. Methods A cross-sectional study of 124 RA patients aged ≥ 18 years, classified per the 2010 ACR/EULAR criteria, collected blood samples for CRP, and antibody levels (RF ≥ 20 IU/ml and anti-CCP ≥ 5 IU/ml via ELISA). Transthoracic echocardiography (TTE) was conducted using a linear method in a long-axis parasternal 2D window. Sixty-two patients exhibited LV remodeling and were matched with 62 patients without it. Echocardiographic variables included were those to calculate the relative wall thickness (RWT, cut-off value 0.42) and left ventricular mass index (LVMI, cut-off values of 43-95 g/m2 in women and 49-115 g/m2 in men) along with left ventricular end diastolic (LVIDd), and systolic volumes (LVIDs), and left ventricular ejection fraction (LVEF). Statistical analyses employed the Chi-square test, Student's t-test, or Mann-Whitney U test as applicable, with correlations assessed using Spearman's rho, an analysis was conducted on the area under the curve (AUC) and a significance level of p ≤ 0.05. Results The most common type of LV alteration in our study was concentric remodeling (74.2%). A statistically significant difference was observed in the levels of Anti-CCP titers 193.85 IU/ml (p &amp;lt; .001), RF IgM 200.00 IU/ml (p &amp;lt; .001) and IgA 185.5 IU/ml (p &amp;lt; .001) in patients with LV remodeling. Anti-CCP and RF IgA antibody levels exhibited a moderate correlation with the presence of LV remodeling, with rho 0.387 (p &amp;lt; .001) and rho 0.344 (p &amp;lt; .001), respectively. The RWT showed a moderate correlation with anti-CCP titers with rho 0.298 (p .001). AUC analysis anti-CCP titers demonstrated better diagnostic performance for the existence of cardiac remodeling (0.722, 95% CI 0.628-0.816, p &amp;lt; .001), RF IgA (0.696, 95% CI 0.602-790, p &amp;lt; .001) and IgM (0.650, 95% CI 0.563-755, p .002). Conclusion In summary, among RA patients without heart failure (HF), LV remodeling and elevated RWT correlate with antibody levels independently of traditional cardiovascular risk factors. Patients with altered LV geometry exhibit higher antibody titers, highlighting the need for RA-related biomarkers that correlate with changes in LV structure and function Recognizing association between autoimmunity and HF development holds significant implications for both prevention and treatment strategies in RA patients.

Surgical reduction of a high-flow dialysis fistula has long-term positive effects of the heart

Abstract Introduction Part of chronic haemodialysis patients develop a high-flow arteriovenous fistula (AVF). The volume overload caused by the presence of a high-flow AVF leads to increased cardiac output, dilation of cardiac chambers, increased pulmonary artery pressure or even to the development of high-output heart failure. Our previous data showed a positive effect of AVF flow-reducing surgery in 6 weeks follow-up. Purpose The purpose of this study was to analyse the long-term effect of AVF blood flow (Qa) reduction on cardiac structure and function. Methods We included patients with high-flow AVFs (defined as Qa over 1500 mL/min) indicated for blood flow reduction surgery for heart failure symptoms or pre-defined echocardiographic changes (left ventricular hypertrophy, severe secondary valvular regurgitations, or pulmonary hypertension). Echocardiography was performed one day before the surgery, the 6 weeks, 6 months, and 12 months thereafter. Qa was measured by ultrasound during the same visits. Results 27 patients were included, 20 men and 7 women, aged 57 ± 13 years. The procedure led to an immediate decrease in Qa. However, we observed failure of the procedure within 1 year in 8 (= 30%) patients defined by increased Qa back to pre-surgery values. Detailed results are displayed in Table 1. Estimated pulmonary arterial systolic pressure and left atrial volume remained significantly lower after 1 year despite the Qa rise. Effective cardiac output (= difference of cardiac output and Qa) rose immediately and remained increased during the follow-up period despite the increase in AVF blood flow. Conclusions We observed a long-time positive effect of AVF blood flow reduction surgery on the heart despite a significant Qa rise. The effective cardiac output remained increased despite the gradual increase of Qa, probably due to the adaptation of systemic arterioles.

Functional status is associated with mean right atrial pressure derived from cardiac MRI

Abstract Background Right atrial pressure (RAP) is a key metric in haemodynamic assessment. Elevated RAP is associated with poor prognosis in heart failure and pulmonary hypertension and physiologically with fluid overload. RAP can be measured invasively or non-invasively, but Cardiac MRI (CMR) currently cannot estimate RAP. Purpose To develop a model to estimate RAP from CMR from paired right heart catheter (RHC) and CMR assessments. Assess correlation to WHO functional status prior to prospective clinical validation studies. Methods Patients were recruited to a registry of those referred for assessment of dyspnoea between 2012 and 2020. Inclusion criteria were age &amp;gt;18 years, signs and symptoms of heart failure and adequate CMR image quality. Patients diagnosed with pulmonary arterial hypertension were excluded. RHC and CMR were performed on the same day. CMR 2- and 4- chamber cines were used to measure chamber dimensions, strain, ejection fraction and stroke volume with operator reviewed AI contours in MASS research software. Pearson’s product-moment correlation coefficient (r ) was used to assess relationships between CMR metrics and invasive mRAP. Variables were then included in stepwise multiple linear regression models to predict mRAP. These were compared with receiver-operator curve analysis and DeLong’s test. Kruskal-Wallis test compared median mRAP between WHO functional class groups. Results The cohort of 672 patients was divided based upon invasive mRAP ≤ 8mmHg (44%) and mRAP &amp;gt; 8mmHg (56%). Higher mRAP was associated with increased age, male sex and a higher diastolic blood pressure but there was no difference in rates of heart failure types although the majority had preserved ejection fraction (51% vs 52%) with few having reduced ejection fraction (4.1% vs 8%). Right atrial (RA) dimensions, strain and ejection fraction had the strongest correlation with mRAP with moderate correlation to right ventricular (RV) measurements. Multivariable models contained simple RA dimensions (model 1), RA dimensions and strain (model 2), RA and RV dimensions (model 3) and RA end systolic volume corrected for body mass index and sex (model 4). All models had similar predictive capability (Figure 1 Panel A). RA end systolic volume was isolated in model 1 as the only variable required for mRAP prediction (coefficient = 0.06, p &amp;lt; 0.001). Using a threshold of mRAP &amp;gt;8mmHg ROC analysis demonstrated an area under the curve of 0.78 (95% Confidence interval 0.75 to 0.81) (Figure 1 Panel B). Worse WHO functional Class at time of assessment was significantly associated with increased CMR derived mRAP (P&amp;lt;0.001) (Figure 2). Conclusions mRAP can be estimated with moderate confidence from CMR RA end systolic volume. Limited available clinical data suggest functional status may be predicted by CMR derived mRAP. Further studies on wider populations are required to validate this model externally, refine it and determine its prognostic clinical significance.

Clec4e deletion in cardiac resident cells leads to smaller infarct size and better cardiac remodeling following myocardial ischemia-reperfusion injury

Abstract Introduction Clec4e-signalling in cardiac resident cells and circulating immune cells stimulates recruitment of proinflammatory leukocytes to infarcted myocardium following ischemia reperfusion injury (I/R) and contributes to ischemic myocardial damage. Clec4e deletion is associated with reduced cardiac injury and better left ventricular structural and functional remodeling. The mechanisms of this cardioprotective effect remain unknown. Research question: We investigated whether Clec4e gene function in cardiac resident cells vs infiltrating immune cells mediates cardioprotection during myocardial ischemia-reperfusion injury. Methods We generated chimeric mice by performing bone marrow transfer in wild type (WT) C57Bl6/J and C57Bl6/J Clec4e-/- mice. Following total body irradiation using 9.5 Gy in 8w-old WT and Clec4e-/- receptor mice, 5 x 10^6 bone marrow cells originating from Clec4e-/- and WT donor mice, respectively, were injected IV. Four weeks later, mice were anesthetized and subjected to ischemia reperfusion injury (I/R) by transient occlusion of the LAD for 60 min. Troponin levels were measured at 90 min post I/R and 7T-magnetic resonance imaging with late gadolinium enhancement (LGE) for infarct size evaluation was performed at 24 hours and 28 days post I/R without LGE. Mice were euthanized at 28 days post I/R and the heart and long shaft bones were processed for postmortem immunohistochemistry and analysis of BM chimerism. Results Immunohistochemical analysis of CLEC4E expression on a bone marrow smear 8 w post bone marrow transfer confirmed successful BM chimerism (7% vs 99%, p&amp;lt;0.01). TnI levels at 90 minutes and LGE assessed infarct size on MRI at 24 hours were not significantly different between groups (n=17 in both groups) (42.1 vs 48.4 ng/ml, and 25.2 vs 31.5% of LVmass in Clec4e-/- mice with WT bone marrow versus in WT mice with Clec4e-/- BM, respectively) suggesting similar myocardial damage . After 28 days, mean LV end diastolic volumes (43µL vs 55µL), and mean end systolic volumes (13µL vs 25µL) were significantly (p&amp;lt;0,05) smaller in Clec4e-/- mice with WT bone marrow resulting in better preserved global LV function (LVEF 62% vs 47%, p&amp;lt;0,05, fig A). Infarct size, semiquantitatively assessed using planimetry on Sirius red stains showed a smaller infarct size in the Clec4e-/- mice with WT bone marrow (6.9% vs 19.8%, p&amp;lt;0.01). Figure B shows a representative example of LGE infarct size to scar tissue on MRI and Sirius red staining. Conclusion Clec4e gene deletion in cardiac resident cells, but not in infiltrating hematopoietic immune cells is associated with better functional and structural remodeling after myocardial I/R. Inhibition of Clec4e signaling via blocking antibodies or small molecule inhibitors in cardiac myocytes might be a promising cardioprotective strategy.

Prognostic yield of echocardiographic measures of cardiac structure and function in HFrEF patients with vs without an ICD or CRT-D

Abstract Background Selected echocardiographic measures of cardiac structure and function are known to be associated with mortality in patients with Heart Failure with reduced Left Ventricular (LV) Ejection Fraction (HFrEF). Whether the predictive ability of measures of cardiac structure and function remain after implantation of an Implantable Cardioverter Defibrillator (ICD) or Cardiac Resynchronization Therapy-Defibrillator (CRT-D) is unknown among patients with HFrEF. Purpose To compare the predictive ability of echocardiographic measures of cardiac structure and function in HFrEF patients with or without an ICD/CRT-D. Methods Echocardiographic examinations were performed between 2003 and 2013 and retrieved from 2168 patients with HFrEF. Patients that had an ICD or CRT-D implanted during follow-up were identified through registries. The endpoint was all-cause mortality and follow-up was 100% to date. Images were analyzed offline in accordance with current guidelines. Associations were assessed by Cox multivariable regression and Cox univariable interaction models. Results After a median of 169 days, 677 patients had an ICD or CRT-D implanted. In total, 68% vs 80% of patients with and without an ICD, respectively, were men (p&amp;lt;0.001) and the median age were 70 vs 71 years (p=0.192). There was a significant difference in resting heart rate (median 74 vs 69, p&amp;lt;0.001) and frequency of ischemic heart disease (64% vs 81%, p&amp;lt;0.001) between the groups. Patients with an ICD had a higher mortality rate (69 per 1000 people/year vs 92 per 1000 people/year, p&amp;lt;0.001) and died significantly faster (median 9.3 vs 8.2 years, p&amp;lt;0.001). Patients with an ICD had higher Left Atrial (LA) End Systolic Volume (59.2 vs 67.3, p&amp;lt;0.001), LA Volume Index (28.5 vs 33.9, p&amp;lt;0.001), LV End Diastolic Volume (137.7 vs 153.7, p&amp;lt;0.001), and LV Mass Index (114.5 vs 124.5, p&amp;lt;0.001), as well as lower LA strain (9.8 vs 6.3, p&amp;lt;0.001) and TAPSE (2.0 vs 1.7, p&amp;lt;0.001). In patients without an ICD, Right Ventricular strain was associated with mortality (HR = 1.05 per 1% decrease mm/m2 [1.005, 1.11] when adjusting for covariates whereas in patients with an ICD, LA Volume Index (HR 1.14 per 1 increase [1.03, 1.25], and LV Ejection Fraction (HR 0.96 per 1% increase [0.92, 0.99]) were associated with mortality when adjusting for covariates. ICD/CRT-D implantation significantly modified the prognostic yield of LV End Diastolic Volume (HR per 1 ml increase: 0.99 without vs 1.01 with an ICD/CRT-D, p=0.005) and LV Mass Index (HR per 1 g/m2 increase: 1.00 without and 1.01 with an ICD/CRT-D, p=0.031). Conclusion Different echocardiographic measures were stronger prognosticators in HFrEF patients with and without an ICD or CRT-D, respectively, and ICD implantation modified the prognostic yield of LV End Diastolic Volume and LV Mass Index in HFrEF patients.Table 1Forest plot

The impact of multimorbidity on cardiac remodelling in the UK Biobank

Abstract Background/Introduction Previous work has suggested that multimorbidity is associated with higher all-cause mortality and cardiovascular mortality in the UK Biobank (UKB). The impact of multimorbidity on cardiac remodelling as measured by cardiovascular magnetic resonance (CMR) has not been studied in large cohorts. Purpose To determine if CMR biomarkers act as surrogates for adverse cardiovascular outcomes in multimorbidity. Method We analysed 44957 UKB participants who had CMR. Self-reported cancer (UKB field ID 20001) and non-cancer illnesses (UKB field ID 20002) were used to calculate comorbidity count with multi-morbidity defined as 2 or more illnesses. The predictive value of comorbidity count (exposure counts measured in quintiles) on CMR traits (outcomes) was evaluated using a univariable and multivariable generalised linear model. Covariates included sex, age, BMI, smoking status, regular alcohol intake, and the Townsend deprivation index, a measure of socioeconomic deprivation. The first model utilised univariable regression without covariates with subsequent iterations including age and sex and then all covariates. An interaction term was included for age and sex and a quadratic term for age in the models. CMR outcome measures were indexed left ventricular mass (LVM), indexed left ventricular end diastolic volume (LVEDV), indexed left ventricular end systolic volume (LVESV), indexed left ventricular stroke volume (LVSV), left ventricular ejection fraction (LVEF), global longitudinal strain (GLS), and indexed maximal left atrial volume (LA). The absolute value of GLS was used in the regression models. Variance inflation factor testing was used to check for collinearity. Analyses were completed using R v4.1.1. Results Median comorbidity count was 2. The burden of long-term conditions in this population of European ancestry with largely healthy individuals is lower than in other large population cohorts. Table 1 summarises multivariable analyses for comorbidity count, LVM and GLS. Due to high collinearity relating to age in the model, we centred age around the mean. LVM was higher with multimorbidity (top quintile Beta 0.63 (95% CI 0.23 to 1.04), P = 2.21x10-03). GLS was lower with multimorbidity (top quintile Beta -0.29 (95%CI -0.42 to 0.16), P = 8.10x10-6). LA volume was lower with multimorbidity (top quintile Beta -0.63(95% CI -1.22 to 0.04), P = 3.53 x 10-2). LVEF and other volume measures were not associated with multimorbidity. Conclusion Multimorbidity in this large cohort was associated with adverse cardiac structural and functional remodelling on CMR. These include a lower global longitudinal strain and higher LV mass.