Left Ventricular End-diastolic Pressure Research Articles

Prognostic Impact of Left Atrial Strain in Patients Hospitalized for Acute Heart Failure With Atrial Fibrillation.

Patients with atrial fibrillation (AF) and heart failure (HF) have elevated left ventricular end-diastolic pressure in addition to decreased left atrial (LA) function, but there are few reports of useful prognostic indices that can be seen on echocardiography. In this study, we investigated the association between LA reservoir strain (LARS) and prognosis in this group of patients. We retrospectively enrolled patients with acute HF complicated by AF who were consecutively admitted to hospital between January 2014 and December 2018. A total of 320 patients (mean age 79±12 years, 163 women) were included in the analysis. During a median follow-up of 473 days, 92 cardiovascular deaths and 113 all-cause deaths occurred. In the multivariate analysis, LARS was an independent predictor of all-cause death (hazard ratio [HR] 0.94, 95% confidence interval [CI] 0.90-0.99, P=0.016). Multivariate analysis also showed that the patients in the lowest LARS tertile (<7.16%) had a significantly increased risk of cardiovascular death (HR 1.76, 95% CI 1.05-2.96; P=0.033) and all-cause death (HR 1.90, 95% CI 1.17-3.08; P=0.009) in comparison with patients in the highest LARS tertile (>10.52%). We found a significant association between LARS and death in patients with AF and HF. Patients with reduced LARS had poor prognosis, suggesting the need for aggressive therapy to improve their LA dysfunction.

The Beneficial Effects of Scrophularia atropatana Methanolic Extract on Myocardial Infarction in Rats

Background: Myocardial infarction (MI) is the leading cause of death among cardiovascular diseases. Reperfusion, the most harmful phase, is accompanied by inflammatory, oxidative, and apoptotic cascades in cardiomyocytes, impairing the hemodynamic and histologic status of the cardiac tissue. The Scrophularia genus is well known for the cardioprotective effects of its species, showing beneficial impacts on blood pressure and arrhythmias in previous studies. Objectives: Regarding the mechanisms involved in MI and the cardioprotective effects of the Scrophularia genus, in this study, we evaluated the cardioprotective effects of Scrophularia atropatana on MI. Methods: Isoproterenol (ISO) injections (100 mg/kg, sc, 24-hour intervals) were used to induce MI in rats. In intervention groups, two hours after the first ISO injection, 5, 10, and 20 mg/kg S. atropatana extract was administered by gavage (24-hour intervals) for three days. Cardiac hemodynamic parameters were measured by placing a catheter into the right carotid artery and the left ventricle. Total antioxidant status (TAS), malondialdehyde (MDA) and lactate levels, and histopathologic changes were evaluated. Results: Induction of MI was accompanied by declined median arterial pressure (MAP), left ventricular systolic pressure (LVSP), and total antioxidant status (TAS) levels. In contrast, the heart rate, left ventricle end-diastolic pressure (LVEDP), malondialdehyde (MDA), and lactate levels were elevated in the MI group. Scrophularia atropatana treatment increased the MAP, LVSP, and TAS levels and significantly reduced the heart rate, LVEDP, MDA, and lactate levels. Also, S. atropatana treatment prevented histopathologic changes post-MI. Conclusions: The improving effects of S. atropatana on MI injuries suggest its potential as a complementary cardioprotective medication.

Three-vessel coronary infusion of cardiosphere-derived cells for the treatment of heart failure with preserved ejection fraction in a pre-clinical pig model.

Heart failure with preserved ejection fraction (HFpEF) is a major public health concern. Its outcome is poor and, as of today, barely any treatments have been able to decrease its morbidity or mortality. Cardiosphere-derived cells (CDCs) are heart cell products with anti-fibrotic, anti-inflammatory and angiogenic properties. Here, we tested the efficacy of CDCs in improving left ventricular (LV) structure and function in pigs with HFpEF. Fourteen chronically instrumented pigs received continuous angiotensin II infusion for 5weeks. LV function was investigated through hemodynamic measurements and echocardiography at baseline, after 3weeks of angiotensin II infusion before three-vessel intra-coronary CDC (n = 6) or placebo (n = 8) administration and 2weeks after treatment (i.e., at completion of the protocol). As expected, arterial pressure was significantly and similarly increased in both groups. This was accompanied by LV hypertrophy that was not affected by CDCs. LV systolic function remained similarly preserved during the whole protocol in both groups. In contrast, LV diastolic function was impaired (increases in Tau, LV end-diastolic pressure as well as E/A, E/E'septal and E/E'lateral ratios) but CDC treatment significantly improved all of these parameters. The beneficial effect of CDCs on LV diastolic function was not explained by reduced LV hypertrophy or increased arteriolar density; however, interstitial fibrosis was markedly reduced. Three-vessel intra-coronary administration of CDCs improves LV diastolic function and reduces LV fibrosis in this hypertensive model of HFpEF.

A new indicator of contrast-induced nephropathy in patients undergoing elective coronary angiography: tissue doppler-derived E/(EA × SA) index.

Hemodynamic instability plays an important role in the development of contrast-induced nephropathy (CIN), which is an important complication of coronary angiography. Left ventricular (LV) end-diastolic pressure (LVEDP) accurately reflects hemodynamic changes. In clinical practice, measuring LVEDP invasively presents some challenges and is not always accessible. This study aimed to investigate the relationship between tissue Doppler-derived early diastolic conduction velocity (E)/[early mitral annular diastolic velocity (Ea), × peak systolic annular velocity (Sa)] index, an important surrogate for LVEDP, and CIN in patients undergoing elective coronary angiography (ECA). This retrospective study included 388 consecutive patients undergoing ECA. CIN was defined as a 25% or 0.5 mg/dL increase in serum creatinine compared to baseline values within 72 hours after ECA. Mehran score was calculated in all patients and systolic and diastolic functions were evaluated with Doppler echocardiography. The incidence of CIN was 9.7%. There was a positive correlation between LV EDP levels and LV E/(Ea × Sa) index (r = 0.691, p < 0.001). Higher LV E/(Ea × Sa) index (OR = 1.03, p < 0.001) and Mehran score (OR = 1.41, p < 0.001) were independent predictors of CIN. The threshold value of LV E/(Ea × Sa) index in predicting CIN was > 1.71 with 75.7% sensitivity and 84.3% specificity (AUC = 0.825). In patients undergoing ECA, the non-invasively measured E/(Ea × Sa) index can be used as a risk indicator for CIN.

Association of Left Ventricular End-Diastolic Pressure With Angiographic Reflow and Short-Term Clinical Outcomes in Patients Presenting with ST-Elevation Myocardial Infarction (STEMI) Undergoing Primary Percutaneous Coronary Intervention (PPCI)

Association of Left Ventricular End-Diastolic Pressure With Angiographic Reflow and Short-Term Clinical Outcomes in Patients Presenting with ST-Elevation Myocardial Infarction (STEMI) Undergoing Primary Percutaneous Coronary Intervention (PPCI)

Role of Systolic Blood Pressure to Left Ventricular End-Diastolic Pressure Ratio in Prediction of Major Adverse Cardiovascular Events in Patients with ST-segment Elevation Myocardial Infarction Treated by Primary Percutaneous Coronary Intervention

Role of Systolic Blood Pressure to Left Ventricular End-Diastolic Pressure Ratio in Prediction of Major Adverse Cardiovascular Events in Patients with ST-segment Elevation Myocardial Infarction Treated by Primary Percutaneous Coronary Intervention

Cinnamaldehyde protects donor heart from cold ischemia–reperfusion injury via the PI3K/AKT/mTOR pathway

With the growing shortage of organs, improvements in donor organ protection are needed to meet the increasing demands for transplantation. Here, the aim was to investigate the protective effect of cinnamaldehyde against ischemia–reperfusion injury (IRI) in donor hearts exposed to prolonged cold ischemia. Donor hearts were harvested from rats pretreated with or without cinnamaldehyde, then subjected to 24 h of cold preservation and 1 h of ex vivo perfusion. Hemodynamic changes, myocardial inflammation, oxidative stress, and myocardial apoptosis were evaluated. The PI3K/AKT/mTOR pathway involved in the cardioprotective effects of cinnamaldehyde was explored through RNA sequencing and western blot analysis. Intriguingly, cinnamaldehyde pretreatment remarkably improved cardiac function through increasing coronary flow, left ventricular systolic pressure, +dp/dtmax, and −dp/dtmax, decreasing coronary vascular resistance and left ventricular end-diastolic pressure. Moreover, our findings indicated that cinnamaldehyde pretreatment protected the heart from IRI by alleviating myocardial inflammation, attenuating oxidative stress, and reducing myocardial apoptosis. Further studies showed that the PI3K/AKT/mTOR pathway was activated after cinnamaldehyde treatment during IRI. The protective effects of cinnamaldehyde were abolished by LY294002. In conclusion, cinnamaldehyde pretreatment alleviated IRI in donor hearts suffering from prolonged cold ischemia. Cinnamaldehyde exerted cardioprotective effects through the activation of the PI3K/AKT/mTOR pathway.

Long-term Ovariectomy Reduces Tolerance of Rats to Myocardial Ischemia-reperfusion Injury.

The harmful impact of ovariectomy on myocardial ischemia-reperfusion (M/IR) injury has been established in the short term. In this study, we aimed to investigate the long-term effects of ovariectomy on M/IR injury. Two methods involving dorsolateral skin incisions were used to induce the ovariectomized (OVX) rat model. The rats were divided into 2 groups: Control and OVX (n = 6). At the end of the study, the hearts were isolated and subjected to global ischemia using the Langendorff apparatus. Cardiac function indices (CFIs) were recorded, including left ventricular end-diastolic pressure (LVEDP), peak rates of positive (+dp/dt) and negative (-dp/dt) changes in LV pressure, and LV-developed pressure (LVDP). At the end of the reperfusion period, the hearts were used to measure the size of the infarct, levels of nitric oxide metabolites (NOx), and mRNA expression of NO synthase (NOS) enzymes, including endothelial (eNOS), neuronal (nNOS), and inducible (iNOS). Compared to controls, OVX rats had larger infarct size by 51%, higher LVEDP by 29%, and lower recovery of +dp/dt, -dp/dt, and LVDP by 29%, 22%, and 35%, respectively. Furthermore, in heart tissue, rats that underwent OVX had significantly higher concentrations of nitrate, nitrite, and NOx by 79%, 82%, and 83%, respectively. Additionally, these rats had lower mRNA levels of eNOS by 38% and higher mRNA levels of iNOS by 71%. The long-term deficiency of estrogen increased the expression of iNOS and decreased the expression of eNOS in the heart tissue of OVX rats. Imbalanced NOS expressions were associated with exacerbated responses to M/IR injury in OVX rats.

Estimating elevated left ventricular end-diastolic pressure by automated left atrial strain analysis in patients with aortic stenosis

Abstract Funding Acknowledgements Type of funding sources: None. Background The evaluation of left ventricular (LV) filling pressure using left atrial (LA) reservoir strain on echocardiography has demonstrated high feasibility and good accuracy. Other LA strain components, such as conduit and booster strain, may show additional diagnostic value for the detection of elevated LV filling pressure. The current automated LA strain analysis has the potential to predict elevated LV end-diastolic pressure (LVEDP) using all LA strain components. Aims The aim of this study is to assess the diagnostic accuracy of automated LA strain for the detection of elevated LVEDP as measured by invasive catherization in comparison to conventional echocardiographic parameters. Methods We included the patients with aortic stenosis (AS) who underwent echocardiography within 48 hours prior to transcatheter aortic valve implantation and had LVEDP measured by catherization during procedure. Patients with atrial fibrillation, previous mitral valve surgery, and mitral stenosis were excluded. LA strain components were measured from apical 4-chamber view using commercial software (AutoStrain LA, Tomtec). (Abstract Picture 1) Elevated LVEDP was defined as a threshold of LVEDP ≥16 mmHg. The cut-off value of conventional echocardiographic parameters for detection of elevated LVEDP were determined according to current guidelines. Results A total of 95 patients (84 ± 7 years, 53% men) were included in this study. Elevated LVEDP was shown in 42 patients. The sensitivity and diagnostic accuracy for the detection of elevated LVEDP on automated LA strain were the best among conventional echocardiographic parameters, including peak reservoir LA strain. (Abstract picture 2) The diagnostic accuracy of automated LA strain was similar between in patients with LV ejection fraction ≥ 50% and those with LV ejection fraction &amp;lt;50% (82% vs 86%). Conclusions Automated LA strain analysis demonstrated superior diagnostic accuracy for the detection of elevated LVEDP in patients with AS. It might thus serve as a non-invasive and accurate alternative method for assessment of elevated LV filling pressure.

Astragaloside IV attenuates cardiac hypertrophy in rats born from mothers with intrauterine hypoxia through the PKCβII/Egr‑1 pathway.

Astragaloside IV (AS-IV) is a naturally occurring agent that confers several wide-ranging reported pharmacological effects, such as cardioprotective, antioxidative and pro-angiogenic activities. Although it was previously reported that AS-IV could attenuate neonatal rat myocardial ischemia-reperfusion injury, the possible effects of AS-IV on the development of cardiac hypertrophy associated with intrauterine hypoxia (IUH) remain unclear. The present study established a model of IHU by placing the pregnant rats in a plexiglass chamber with an oxygen supply of 10% before neonatal rat delivery. To investigate the in vivo effect of AS-IV on cardiac hypertrophy, neonatal rats with hypertension were randomly grouped to receive AS-IV (20 mg/kg), AS-IV (40 mg/kg), AS-IV (80 mg/kg) or vehicle for 12 weeks, followed by left ventricular (LV) hemodynamics and heart tissue histological analysis. Rats born from mothers with IHU displayed pathological features of cardiac hypertrophy. However, AS-IV 40 and 80 mg/kg significantly decreased the heart/body weight (BW), LV mass (LVM)/BW, heart mass/tibia length (TL) and LVM/TL ratios. H&E staining showed that 40 and 80 mg/kg AS-IV prevented the morphometric changes induced by IHU. According to data from LV hemodynamics measurements, AS-IV 80 mg/kg reversed the increased systolic blood pressure, diastolic blood pressure, LV systolic pressure, LV end-diastolic pressure, dP/dt maximum and heart rate induced by IHU. Mechanistically, ERK1/2 activation and early growth response 1 (Egr-1) protein expression were both upregulated by IHU induction, which was reversed by AS-IV treatment. In conclusion, these data suggested that AS-IV could attenuate cardiac hypertrophy in neonatal rats born from mothers with IHU through the protein kinase C β type isoform 2/Egr-1 pathway, but the underlying mechanism requires further investigation.

Sevoflurane exerts protection against myocardial ischemia–reperfusion injury and pyroptosis through the circular RNA PAN3/microRNA-29b-3p/stromal cell-derived factor 4 axis

ObjectiveSevoflurane is suggested to exert protective functions against myocardial ischemia–reperfusion injury (MIRI). However, the particular mechanism remains elusive. Therefore, this research explored the mechanism of sevoflurane in MIRI-induced damage and pyroptosis. MethodsSubsequent to gain-or loss-of-function assays or/and sevoflurane treatment, the MIRI model was developed in rats. Cardiac function and body and heart weight of rats were evaluated, followed by measurement of apoptosis and creatine kinase MB (CK-MB), lactate dehydrogenase (LDH), and pyroptosis-related protein levels. After loss-of-function assays or/and sevoflurane treatment in human cardiomyocytes (HCMs), the hypoxia/reoxygenation (H/R) model was constructed. In HCMs, cell viability, apoptosis, and pyroptosis-related proteins were detected. Circular RNA PAN3 (circPAN3), microRNA (miR)-29b-3p, and stromal cell-derived factor 4 (SDF4) expression was determined in rat myocardial tissues and HCMs. Mechanistically, interactions among circPAN3, miR-29b-3p, and SDF4 were analyzed. ResultsMIRI modeling increased miR-29b-3p expression and diminished circPAN3 and SDF4 expression in H/R-treated HCMs and MIRI rats, which was nullified by sevoflurane preconditioning. Mechanistically, circPAN3 negatively targeted miR-29b-3p to upregulate SDF4. Moreover, sevoflurane preconditioning reduced heart weight/body weight ratio, LDH, CK-MB, myocardial infarct size, left ventricular end-diastolic pressure, apoptosis, and pyroptosis, while elevating the increase and decrease of left ventricular pressure (±dp/dt max) and left ventricular systolic pressure in MIRI rats. In addition, sevoflurane preconditioning augmented viability while diminishing apoptosis and pyroptosis in H/R-treated HCMs. Moreover, circPAN3 silencing or miR-29b-3p overexpression abrogated alleviatory effects of sevoflurane on myocardial injury and pyroptosis in vitro. ConclusionSevoflurane treatment ameliorated myocardial injury and pyroptosis in MIRI via circPAN3/miR-29b-3p/SDF4 axis.

BIO6: Acute In Vivo Studies of the Left Atrial Assist Device and Simulated Diastolic Heart Failure

Purpose: The Left Atrial Assist Device (LAAD) is a mixed-flow pump in development for patients who have diastolic heart failure (DHF). The device is implantable in the mitral plane and delivers blood from the left atrium to the left ventricle to mitigate high left atrial pressure. The purpose of this study was to assess the operational in vivo performance of the LAAD with simulated DHF conditions. Methods: The LAAD was implanted in calves (n=8; mean weight 84.5 kg) using cardiopulmonary bypass (CPB) support through a left atrial incision. Various pump-operating conditions, including mean pump speeds ranging from 3,600 to 5,200 rpm and three DHF conditions with a balloon (0, 50 and 70 mL) inflated inside the left ventricle, were tested and evaluated. The hemodynamics for each pump setting were recorded. As for the DHF conditions, the effect of the balloon inflation was evaluated before and after the LAAD implantation in 5 cases (mean weight 89.1 kg) among the 8 calves. Results: The LAAD responded to all control inputs and ran as expected during the experiment. Anatomical fit of the LAAD was suitable for all hearts, but some suction events were occasionally observed at speeds over 4,400 rpm, mainly due to of the small size of the normal left atrium. For the simulated DHF conditions, the baseline data (without LAAD) showed lower cardiac output and aortic pressure (Fig 1A and 1B) and higher LAP and left ventricle end diastolic pressure (Fig 1C and 1D) as the DHF conditions increased in severity. The LAAD seemed to mitigate the severity of the simulated DHF hemodynamics (Fig 1A-D). Conclusion: The acute implantations of the LAADs in calves were successful, and the pump showed improvement of the hemodynamics in the simulated DHF conditions. Additional studies, including chronic evaluations are underway.Figure 1. The in vivo hemodynamics changes under 50 and 70 mL of balloon inflation compared with no balloon inflation. A: Cardiac output (CO), B: Arterial pressure (AoP), C: Left atrial pressure (LAP), and D: Left ventricular end-diastolic pressure (LVEDP).

Coronary artery disease is associated with impaired atrial function regardless of left ventricular filling pressure

BackgroundLeft atrial (LA) strain is impaired in left ventricular (LV) diastolic dysfunction, associated with increased LV end diastolic pressure (LVEDP). In patients with preserved LV ejection fraction (LVEF), coronary artery disease (CAD) is known to impair LV diastolic function. The relationship of LVEDP with CAD and impact on LA strain is not well studied. Methods and resultsPatients with LVEF >50% (n = 37, age 61 ± 7 years) underwent coronary angiography, high-fidelity LV pressure measurements and cardiac magnetic resonance imaging. LA volumes, LA emptying fraction (LAEF), LA reservoir strain (LARS) and LA long-axis shortening (LALAS) were measured. By coronary angiography, patients were assigned into 3 groups: severe-CAD (n = 19, with obstruction of major coronary arteries >70% and/or history of coronary revascularization), mild-to-moderate-CAD (n = 10, obstruction of major coronary arteries 30–60%), and no-CAD (n = 8, obstruction of major coronary arteries and branches <30%). Overall, LVEF was 65 ± 8% and LVEDP was 14.4 ± 5.6 mmHg. Clinical characteristics, LVEDP and LV function measurements were similar in 3 groups. Severe-CAD group had lower LAEF, LALAS and LARS than those in no-CAD group (P < 0.05 all). In regression analysis, LARS and LALAS were associated with CAD severity and treatment with Nitrates, whereas LAEF and LAEFactive were associated with CAD severity, treatment with Nitrates and LA minimum volume (P < 0.05 all). LAEFpassive was associated with LVED volume (P < 0.05). ConclusionsLA functional impairment may be affected by coexistent CAD severity, medications, in particular, Nitrates, and loading conditions, which should be considered when assessing LA function and LA-LV interaction. Our findings inspire exploration in a larger cohort.

Metabolomics analysis in rat hearts with ischemia/reperfusion injury after diazoxide postconditioning.

Background: Diazoxide is a selective mitochondrial-sensitive potassium channel opening agent that has a definite effect on reducing myocardial ischemia/reperfusion injury (MIRI). However, the exact effects of diazoxide postconditioning on the myocardial metabolome remain unclear, which might contribute to the cardioprotective effects of diazoxide postconditioning. Methods: Rat hearts subjected to Langendorff perfusion were randomly assigned to the normal (Nor) group, ischemia/reperfusion (I/R) group, diazoxide (DZ) group and 5-hydroxydecanoic acid + diazoxide (5-HD + DZ) group. The heart rate (HR), left ventricular developed pressure (LVDP), left ventricular end-diastolic pressure (LVEDP), and maximum left ventricular pressure (+dp/dtmax) were recorded. The mitochondrial Flameng scores were analysed according to the ultrastructure of the ventricular myocardial tissue in the electron microscopy images. Rat hearts of each group were used to investigate the possible metabolic changes relevant to MIRI and diazoxide postconditioning. Results: The cardiac function indices in the Nor group were better than those in the other groups at the end point of reperfusion, and the HR, LVDP and +dp/dtmax of the Nor group at T2 were significantly higher than those of the other groups. Diazoxide postconditioning significantly improved cardiac function after ischaemic injury, and the HR, LVDP and +dp/dtmax of the DZ group at T2 were significantly higher than those of the I/R group, which could be abolished by 5-HD. The HR, LVDP and +dp/dtmax of the 5-HD + DZ group at T2 were significantly lower than those of the DZ group. The myocardial tissue in the Nor group was mostly intact, while it exhibited considerable damage in the I/R group. The ultrastructural integrity of the myocardium in the DZ group was higher than that in the I/R and 5-HD + DZ groups. The mitochondrial Flameng score in the Nor group was lower than that in the I/R, DZ and 5-HD + DZ groups. The mitochondrial Flameng score in the DZ group was lower than that in the I/R and 5-HD + DZ groups. Five metabolites, namely, L-glutamic acid, L-threonine, citric acid, succinate, and nicotinic acid, were suggested to be associated with the protective effects of diazoxide postconditioning on MIRI. Conclusion: Diazoxide postconditioning may improve MIRI via certain metabolic changes. This study provides resource data for future studies on metabolism relevant to diazoxide postconditioning and MIRI.

Disagreement of ESC guidelines from 2016 and 2021 and HFA-PEFF and H2 FPEF scores in diagnosis of heart failure with preserved ejection fraction in atrial fibrillation patients

Abstract Funding Acknowledgements Type of funding sources: None. Background Heart failure with preserved ejection fraction (HFpEF) frequently coexists with atrial fibrillation (AF). The gold-standard test for HFpEF diagnosis remains invasive assessment of left ventricular end-diastolic pressures but noninvasive diagnostic scoring systems have been developed to aid accurate diagnosis. However, the diagnosis of HFpEF in patients with AF is more difficult because some diagnostic criteria for HFpEF may be associated with AF instead of HFpEF per se. Purpose To compare the guidelines and scoring systems for HFpEF diagnosis in patients with AF, and to indicate the most relevant clinical and echocardiographic parameters supporting the diagnosis of HFpEF in an AF cohort. Methods Consecutive patients with paroxysmal or persistent AF scheduled for catheter ablation were included. Clinical characteristics and transthoracic echocardiography examination was collected at baseline visit. The European Society of Cardiology (ESC) guidelines from 2016 and 2021 as well as scoring systems (HFA-PEFF and H2FPEF scores) were used to diagnose HFpEF. In the H2FPEF score, patients with AF alone, score of 3, were assessed as group with the low risk for HFpEF (instead of intermediate risk according to the H2FPEF score), as all enrolled patients had AF. Multiple logistic regression was performed to find optimal parameters predicting HFpEF, that was defined as diagnosis of HFpEF according to all following scores: ESC guidelines from 2016 and 2021 and high risk in HF2FPEF and HF-PEFF scores. Results We analysed 325 patients (median age 65 [59-72], 36% women). Considerable differences were observed in HFpEF diagnoses when stratifying patients according to ESC 2016 and ESC 2021 guideline definitions; the percentage of HFpEF patients reduced from 55% (n=180) to 28% (n=90). The agreement of HF2PEF score relative to HFA-PEFF score was 46% (n=25/55), 54% (n=115/213) and 35% (n=20/57) of patients regarding low, intermediate and high risk for HFpEF, respectively. Overall, 5.8% of patients (n=19) had HFpEF (Figure 1). These 19 patients were older (median age 70 vs 65, p&amp;lt;0.001), had more often persistent AF (63% vs 30%; p&amp;lt;0.001) and vascular disease (37% vs 14%, p=0.017) as compared to those without HFpEF. Based on multiple logistic regression, higher values of N-terminal-pro hormone BNP (NT-proBNP; OR 1.02, 95CI 1.01-1.03) and LA volume index (LAVI; OR 1.13, 95%CI 1.04-1.23) were independent predictors of having HFpEF in AF population. The NT-proBNP of 45 pmol/L and LAVI of 45ml/kg2 were ideal cutoffs and constructed a model to predict HFpEF which fitted with a concordance index of 0.91 (95% CI 0.87–0.94) (Figure 2). Conclusions The differences in HFpEF definition in the guidelines and various scoring systems lead to considerable difference in stratification of HFpEF in AF patients. In our population, just 5.8% of AF patients were diagnosed with HFpEF regarding ESC guidelines and high risk for HFpEF in scoring systems.

Improvement in cerebral oxygen saturation with sinus conversion during off pump coronary artery bypass graft: A case report.

Near-infrared spectroscopy (NIRS) is a noninvasive bedside tool for monitoring regional cerebral oxygen saturation (rSO2). The sinus conversion of atrial fibrillation (AF) was shown to be responsible for increasing rSO2. However, the reason for this improvement has not yet been clearly explained. We report the case of a 73-year-old woman who underwent cardioversion during an off-pump coronary artery bypass under NIRS and live hemodynamic monitoring. Unlike previous studies that failed to control and compare all conditions during procedures, this case showed real-time fluctuating hemodynamic and hematological values, such as hemoglobin (Hgb), central venous pressure (CVP), mean arterial pressure (MAP), cardiac index (CI), left ventricular end-diastolic pressure (LVEDP), and SVO2. The rSO2 increased immediately after cardioversion and decreased during the obtuse marginal (OM) graft and after AF was obtained. However, no other hemodynamic data showed the same or opposite directional changes in the rSO2. Significant instantaneous changes were observed in rSO2 using NIRS after sinus conversion, without obvious hemodynamic alterations in the systemic circulation or other monitoring values.

Characterization of a robust mouse model of heart failure with preserved ejection fraction.

Heart failure (HF) is a leading cause of morbidity and mortality particularly in older adults and patients with multiple metabolic comorbidities. Heart failure with preserved ejection fraction (HFpEF) is a clinical syndrome with multisystem organ dysfunction in which patients develop symptoms of HF as a result of high left ventricular (LV) diastolic pressure in the context of normal or near normal LV ejection fraction (LVEF; ≥50%). Challenges to create and reproduce a robust rodent phenotype that recapitulates the multiple comorbidities that exist in this syndrome explain the presence of various animal models that fail to satisfy all the criteria of HFpEF. Using a continuous infusion of angiotensin II and phenylephrine (ANG II/PE), we demonstrate a strong HFpEF phenotype satisfying major clinically relevant manifestations and criteria of this pathology, including exercise intolerance, pulmonary edema, concentric myocardial hypertrophy, diastolic dysfunction, histological signs of microvascular impairment, and fibrosis. Conventional echocardiographic analysis of diastolic dysfunction identified early stages of HFpEF development and speckle tracking echocardiography analysis including the left atrium (LA) identified strain abnormalities indicative of contraction-relaxation cycle impairment. Diastolic dysfunction was validated by retrograde cardiac catheterization and analysis of LV end-diastolic pressure (LVEDP). Among mice that developed HFpEF, two major subgroups were identified with predominantly perivascular fibrosis and interstitial myocardial fibrosis. In addition to major phenotypic criteria of HFpEF that were evident at early stages of this model (3 and 10 days), accompanying RNAseq data demonstrate activation of pathways associated with myocardial metabolic changes, inflammation, activation of extracellular matrix (ECM) deposition, microvascular rarefaction, and pressure- and volume-related myocardial stress.NEW & NOTEWORTHY Heart failure with preserved ejection fraction (HFpEF) is an emerging epidemic affecting up to half of patients with heart failure. Here we used a chronic angiotensin II/phenylephrine (ANG II/PE) infusion model and instituted an updated algorithm for HFpEF assessment. Given the simplicity in generating this model, it may become a useful tool for investigating pathogenic mechanisms, identification of diagnostic markers, and for drug discovery aimed at both prevention and treatment of HFpEF.

Mitochondrial dysfunction and cardiac ischemia/reperfusion injury are attenuated by nandrolone: Role of JAK-STAT3 pathway

AimTo investigate the effect of acute treatment with the anabolic steroid (AS) nandrolone decanoate in mitochondrial homeostasis and JAK-STAT3 signaling during the progression of cardiac ischemia/reperfusion injury (IR). MethodsMale Wistar rats (2 months old) were randomly allocated into four experimental groups: Control (CTRL), IR, AS, and AS + AG490. All animals were euthanized 3 days after a single intramuscular injection of nandrolone at 10 mg/kg (AS and AS + AG490 groups) or vehicle (CTRL and IR groups). Baseline mRNA expression of antioxidant enzymes superoxide dismutase (SOD) 1 and 2, glutathione peroxidase, catalase, and myosin heavy chain (MHC) α and β were compared between CTRL and AS groups. Isolated hearts were submitted to ex vivo ischemia and reperfusion, except for hearts from the CTRL group. Before the IR protocol, the JAK-STAT3 inhibitor AG490 was perfused in hearts from the AS + AG490 group. Heart samples were collected during reperfusion to investigate the effects on mitochondrial function.ResultsAntioxidant enzyme mRNA expression was unaffected, whereas the AS group exhibited decreased β- MHC/α-MHC ratio versus the CTRL group. Compared to the IR group, the AS group exhibited better recovery of post-ischemic left ventricular (LV) end-diastolic pressure and LV-developed pressure levels, while infarct size significantly decreased. Furthermore, mitochondrial production, transmembrane potential, and swelling were improved, whereas ROS formation was decreased versus the IR group. These effects were prevented by the perfusion of JAK-STAT3 inhibitor AG490. ConclusionThese findings suggest that acute nandrolone treatment can provide cardioprotection by recruiting the JAK-STAT3 signaling pathway and mitochondrial preservation.

The impact of aortic valve regurgitation on the combination therapy of VA-ECMO and Imeplla support in severe cardiogenic shock: a simulation study

Background: The utilization of a combination of veno-arterial extracorporeal membrane oxygenation (VA-ECMO) and Impella, ECPELLA, has become widespread among patients with cardiogenic shock. The utilization of VA-ECMO in the presence of aortic regurgitation (AR) can result in significant left ventricular (LV) distention. Additionally, the implantation of Impella via the aortic valve frequently induces AR clinically. We established a simulation model and evaluated the impact of AR on hemodynamics under ECPELLA. Furthermore, assuming that the reverse flow of AR is strongly determined by aortic pressure (AP) level, we simulated a scenario where AP was further decreased. Methods: We employed Simulink® (Mathworks, Inc.). The systemic and pulmonary circulations were modeled using a 5-element resistance-capacitance network. Four cardiac chambers were represented by time-varying elastance. We compared the aortic regurgitant flow (Far), total systemic flow (Ftotal), and LV pressure-volume relationship under various severities of AR and varying Impella (0-3.7 L/min) and VA-ECMO (0-5 L/min) flows. AR grades were adjusted by the regurgitant resistance and classified as mild, moderate, and severe, mimicking a clinical scenario. Results: Without AR, ECMO significantly increased Ftotal and raised LV end-diastolic pressure (LVEDP). Impella increased Ftotal and decreased LVEDP. The concomitant presence of AR exacerbated the increase of LVEDP by ECMO and the reduction of LVEDP by Impella. Under ECPELLA support (VA-ECMO: 3 L/min) with mild AR, the increase of Impella support (1 to 3.5 L) increased Ftotal and Far, while decreasing LVEDP, indicating the prevention of AR-induced LV distention. Additionally, the presence of mild AR prevented the Impella-induced left ventricular suction that is commonly observed under ECPELLA support with high-flow VA-ECMO. In the case of moderate AR, while the hemodynamic trends were similar to those observed under mild AR, Impella was unable to prevent the increment of LVEDP to a critical level (&lt; 20 mmHg). However, by decreasing AP through reducing resistance (e.g. vasodilators), both Far and LVEDP were dramatically reduced and Ftotal was increased under ECPELLA support. Conclusion: The concomitant presence of AR in ECPELLA condition increased LV load, while prevented LV suction. The use of vasodilator in ECPELLA with AR could attenuate AR, increase systemic perfusion, and reduce LV load. The optimal control of Impella and VA-ECMO flows and AP can maximize the hemodynamic and LV unloading impacts of ECPELLA. no funding 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.

PO-01-208 A COMPUTATIONAL MODEL TO TRACK CHANGES IN LEFT VENTRICULAR END-DIASTOLIC PRESSURE DURING ATRIAL FIBRILLATION

Heart failure and Atrial Fibrillation (AF) commonly occur concomitantly, resulting in significant morbidity and mortality. Thus, monitoring of heart failure status is essential in directing medical therapy in these patients. Left ventricular (LV) filling pressures are one of the most important parameters in assessing worsened or acutely decompensated left heart failure, however current LV pressure monitoring strategies include invasive devices and catheterization. Our study aims to develop a computational model of heart failure in AF and demonstrate that beat-to-beat variations in RR intervals during AF can be exploited to predict changes in LV filling pressure. We used a modified Research CardioVascular SIMulator (RCVSIM) human cardiovascular model to simulate an intact circulatory system in patients with AF over 300 seconds. To simulate beat-by-beat variation of rhythm in AF, the length of each RR-interval was drawn randomly from a Mixed Gaussian Distribution. We modelled worsening HF by changing LV end-systolic compliance in the simulator, using compliances ranging from 1 to 3.5 mL/mmHg, with interval increases in compliance of 0.1 mL/mmHg. Stroke volumes, RR-intervals, and LV end-diastolic pressures are recorded for each simulation. This was repeated for mean heart rates from 60 to 110 beats per minute. Stroke volumes were found to have a strong linear correlation with the previous beat’s RR-interval for all mean heart rates tested (Spearman rho = 0.9-0.97). In Figure 1 below, we show the slope of the RR-interval versus stroke volume (SV/RR-interval) plotted against average LV end-diastolic pressure for all LV systolic compliances noted above and a mean heart rate of 84 beats per minute. A cubic function fit to this plot shows excellent goodness-of-fit with the simulated data with a coefficient of determination (R2) of 0.99. This relationship remained consistent for all mean heart rates tested, and all cubic fits had R2 greater than 0.98. Our study provides a highly accurate model for estimating LV end-diastolic pressures over a broad range of LV systolic heart failure in simulated AF patients using only stroke volume and RR-intervals. Further work using photoplethysmography or continuous non-invasive arterial pressure (CNAP) monitoring could potentially be used to obtain these measures non-invasively, thus leading to a non-invasive method for tracking heart failure in patients with AF.