Left Ventricular End-diastolic Pressure Research Articles

Contrast media volume reduction with the DyeVertTM system to prevent acute kidney injury in stable patients undergoing coronary procedures.

Contrast associated acute kidney injury (CA-AKI) can lead to an increased risk of adverse events. Contrast media (CM) volume reduction has been advocated as a pivotal strategy to prevent CA-AKI in stable patients undergoing percutaneous coronary procedures. To compare the effectiveness of CM volume reduction with the DyeVertTM system versus conventional strategy in reducing the risk of CA-AKI. We prospectively collected data from 136 patients with stable coronary artery disease at high risk of CA-AKI treated with left ventricular end diastolic pressure (LVEDP)- guided hydration and undergoing interventions with the use of the DyeVertTM (Osprey Medical Inc.) system. Patients previously enrolled in the LVEDP-guided hydration arm of the "Renal Insufficiency Following Contrast MEDIA Administration triaL III" (REMEDIAL III) were considered as controls. Propensity score was used to perform 1:1 matching to adjust for major confounders. The primary outcome was the occurrence of CA-AKI, as defined by an absolute increase of creatinine values ≥0.3 mg/dL at 48 h. Patients in the DyeVert group were treated with a significant lower CM volume (median: 47.5 vs. 84.0 mL, p < 0.001). The trend in creatinine increase was lower (p = 0.004) and the Δ of creatinine (0-48 h) showed a higher drop (-0.18 vs. -0.10 mg/dL, p = 0.036) in the DyeVert group. The risk of CA-AKI was significantly lower in DyeVert group compared to control group (5.1% vs. 16.8%; odds ratio 0.27, 95% confidence interval [0.12-0.61]). CM volume reduction with the DyeVertTM system seems to be superior to conventional strategies in reducing the occurrence of CA-AKI.

Left atrial strain as a predictor of left ventricular filling pressures in coronary artery disease with preserved ejection fraction: a comprehensive study with left ventricular end-diastolic and pre-atrial contraction pressures.

Assessing left ventricular (LV) filling pressure (LVFP) is challenging in patients with coronary artery disease (CAD) and preserved LV ejection fraction (LVEF). We aimed to correlate left atrial strain (LAS) with two invasive complementary parameters of LVFP and compared its accuracy to other echocardiographic data to predict high LVFP.This cross-sectional, single-center study enrolled 81 outpatients with LVEF > 50% and significant CAD from a database. Near-simultaneous echocardiography and invasive measurements of both LV end-diastolic pressure (LVEDP) and LV pre-atrial contraction (pre-A) pressure were performed in each patient, based on the definition of LVEDP > 16 mmHg and LV pre-A > 12 mmHg as high LVFP.A moderate to strong correlation was observed between LAS reservoir (LASr), contractile strain, and LVEDP (r: 0.67 and 0.62, respectively; p < 0.001); the same was true for LV pre-A (r: 0.65 and 0.63, respectively; p < 0.001). LASr displayed good diagnostic performance to identify elevated LVFP, which was higher when compared to traditional parameters. Median value of LASr was higher for an isolated increase of LVEDP than for simultaneously high LV pre-A. The cutoff found to predict high LVFP was lower for LV pre-A than that one for LVEDP. In the current study, LASr did not provide an additional contribution to the 2016 diastolic function algorithm.LAS is a valuable tool for predicting LVFP in patients with CAD and preserved LVEF. The choice of LVEDP or LV pre-A as the representative marker of LVFP leads to different cutoffs to predict high pressures. The best strategy for adding this tool to a multiparametric algorithm requires further investigation.

Abstract 103: Combined Dapagliflozine And Eplerenone Treatment Improve Cardiorenal Function In Rats With Chronic Kidney Disease.

Background: Patients with chronic kidney disease (CKD) present higher risk of cardiovascular (CV) complications as well as renal function decline. The DAPA-CKD trial showed reduced CV events in diabetic and non-diabetic CKD patients treated with Dapagliflozine (DAPA). Mineralocorticoid Receptor Antagonists (MRAs) have shown similar beneficial effects in diabetic CKD patients (FIDELIO-CKD &amp; FIGARO-CKD trials) but impact in non-diabetic CKD patients is unkown. The aim of this study was to compare DAPA and Eplerenone (EPLE), alone or in combination on renal and CV functions in a non-diabetic rat CKD model. Methods: CKD was induced in Sprague Dawley rats by 5/6 nephrectomy. Rats were treated with DAPA (10 mg/kg/day PO), EPLE (100 mg/kg/day PO) or the combination during 3 months. Results: After 3 months kidney fibrosis is decreased in the 3 treated groups compared to untreated CKD. No changes of creatinine clearance were observed while albuminuria increased in the DAPA groups with no significant effects of EPLE. The fractional shortening and the cardiac output were not modified by the treatments (not shown). Cardiac hemodynamic was improved with reduced LV end diastolic pressure (LVEDP) in the CKD rats treated with EPLE or a combination of EPLE and DAPA while LV end diastolic pressure volume relationship (LVEDPVR) was decrease by both DAPA and EPLE and further decreased by DAPA + EPLE. Decreased cardiac perfusion was prevented with EPLE alone or with the combination. Conclusion: The use of DAPA + EPLE appears to be more effective than DAPA or EPLE alone on diastolic function in non-diabetic CKD rats while cardiac perfusion is improved by EPLE only.

Abstract 080: The Non-steroidal Mineralocorticoid Receptor Antagonist Finerenone Improves Diastolic Dysfunction In Preclinical Non-diabetic Chronic Kidney Disease

Background: The mineralocorticoid receptor (MR) plays an important role in the development of Chronic Kidney Disease (CKD) and its overactivation contributes to the progression of cardiovascular complications. Antagonizing the overactivation of the MR with MR antagonists (MRA) is a therapeutic option. Finerenone, is a non-steroidal MRA recently studied in two large clinical trials showing the beneficial effects lowering the risks of CKD progression and cardiovascular events in stage 1 to 4 CKD patients with type 2 diabetes (T2D) (FIDELIO-DKD and FIGARO-DKD trials) Aim: To test whether finerenone improves renal and/or cardiac functions in preclinical non-diabetic CKD. Methods: non-diabetic CKD was induced by 5/6 nephrectomy in 6 weeks old Sprague Dawley rats. Finerenone (10 mg/kg/day) was administered as preventive or as curative treatment. Left ventricle (LV) function/hemodynamics, LV tissue perfusion and GFR were assessed in vivo at the age of 24 weeks. Results: 12 weeks after 5/6 nephrectomy, the rats showed classical signs of CKD: reduced GFR and increased kidney weight; associated with LV diastolic dysfunction confirmed by increased in LV end-diastolic pressure (LVEDP), LV relaxation constant (Tau) and LV end-diastolic pressure volume-relation (LVEDPVR), while LV perfusion was reduced. Both prevention and curative treatment with finerenone reduced significantly both LVEDPVR and Tau; and increased LV tissue perfusion. Finerenone treatment did not impact reduced kidney GFR but reduced renal hypertrophy. Conclusion: Both preventive and curative finerenone improves non-diabetic CKD related LV diastolic function, independently from changes in kidney function.

Metformin effects on cardiac parameters in non-diabetic Iraqi patients with heart failure and mid-range ejection fraction - a comparative two-arm parallel clinical study.

Heart failure (HF) remains a difficult challenge to the healthcare system, necessitating promoting interventions and multidrug management. Metformin, typically used to manage diabetes, has emerged as a promising intervention in the treatment of HF. This study aimed to assess the effect of adding metformin to the standard treatment of HF on cardiac parameters. This clinical study comprised 60 newly diagnosed HF patients randomly assigned to two groups: Group C received standard HF treatment, while Group M received standard HF treatment in addition to daily metformin (500 mg). After 3 months of treatment, group M showed a significantly higher ejection fraction (EF) compared to Group C (6.1% and 3.2%, respectively; p-value=0.023) and a reduction in the left ventricular end-diastolic pressure (LVEDD) (0.28, and 0.21 mm respectively; p-value=0.029). No significant differences were observed in the interventricular septal thickness (IVST) or left ventricular end-systolic pressure (LVESD). For cardiac markers, N-Terminal pro-BNP (NT-proBNP) showed the highest reduction in Group M compared to Group C (719.9 pg/ml and 271.9 pg/ml respectively; p-value=0.009). No significant changes were reported for soluble ST2. Metformin demonstrated cardiac protective effects by increasing EF and reducing NT-proBNP. Given its affordability and accessibility, metformin offers a valuable addition to the current HF treatment options. This positive effect may be attributed to mechanisms that enhance the impact of conventional HF treatments or vice versa.

Cardioprotective effect of naringin against the ischemia/reperfusion injury of aged rats.

Aging is known as a main risk factor in the development of cardiovascular diseases. Naringin (NRG) is a flavonoid compound derived from citrus fruits. It possesses a wide spectrum of pharmacological properties, including antioxidant anti-inflammatory, and cardioprotective. This investigation aimed to assess the cardioprotective effect of NRG against the ischemia/reperfusion (I/R) injury in aged rats. In this study, D-galactose (D-GAL) at the dose of 150 mg/kg/day for 8 weeks was used to induce aging in rats. Rats were orally gavaged with NRG (40 or 100 mg/kg/day), in co-treatment with D-GAL, for 8 weeks. The Langendorff isolated heart was used to evaluate the effect of NRG on I/R injury in aged rats. NRG treatment diminished myocardial hypertrophy and maximum contracture level in aged animals. During the pre-ischemic phase, reduced heart rate was normalized by NRG. The effects of D-GAL on the left ventricular end diastolic pressure (LVDP), the rate pressure product (RPP), and the minimum and maximum rate of left ventricular pressure (±dp/dt) improved by NRG treatment in the perfusion period. NRG also enhanced post-ischemic recovery of cardiac functional parameters (± dp/dt, and RPP) in isolated hearts. An increase in serum levels of the lactate dehydrogenase (LDH), the creatine kinase-MB (CK-MB), and the tumor necrosis factor-alpha (TNF-α) were reversed by NRG in aged rats. It also normalized the D-GAL-decreased the superoxide dismutase (SOD) activity in the heart tissue. NRG treatment alleviated cardiac injury in aged hearts under conditions of I/R. NRG may improve aging-induced cardiac dysfunction through anti-oxidative and anti-inflammatory mechanisms.

Vagus nerve stimulation-induced stromal cell-derived factor-l alpha participates in angiogenesis and repair of infarcted hearts.

We aim to explore the role and mechanism of vagus nerve stimulation (VNS) in coronary endothelial cells and angiogenesis in infarcted hearts. Seven days after rat myocardial infarction (MI) was prepared by ligation of the left anterior descending coronary artery, the left cervical vagus nerve was treated with electrical stimulation 1h after intraperitoneal administration of the α7-nicotinic acetylcholine inhibitor mecamylamine or the mAChR inhibitor atropine or 3days after local injection of Ad-shSDF-1α into the infarcted heart. Cardiac tissue acetylcholine (ACh) and serum ACh, tumour necrosis factor α (TNF-α), interleukin 1β (IL-1β) and interleukin 6 (IL-6) levels were detected by ELISA to determine whether VNS was successful. An inflammatory injury model in human coronary artery endothelial cells (HCAECs) was established by lipopolysaccharide and identified by evaluating TNF-α, IL-1β and IL-6 levels and tube formation. Immunohistochemistry staining was performed to evaluate CD31-positive vessel density and stromal cell-derived factor-l alpha (SDF-1α) expression in the MI heart in vivo and the expression and distribution of SDF-1α, C-X-C motif chemokine receptor 4 and CXCR7 in HCAECs in vitro. Western blotting was used to detect the levels of SDF-1α, V-akt murine thymoma viral oncogene homolog (AKT), phosphorylated AKT (pAKT), specificity protein 1 (Sp1) and phosphorylation of Sp1 in HCAECs. Left ventricular performance, including left ventricular systolic pressure, left ventricular end-diastolic pressure and rate of the rise and fall of ventricular pressure, should be evaluated 28days after VNS treatment. VNS was successfully established for MI therapy with decreases in serum TNF-α, IL-1β and IL-6 levels and increases in cardiac tissue and serum ACh levels, leading to increased SDF-1α expression in coronary endothelial cells of MI hearts, triggering angiogenesis of MI hearts with increased CD31-positive vessel density, which was abolished by the m/nAChR inhibitors mecamylamine and atropine or knockdown of SDF-1α by shRNA. ACh promoted SDF-1α expression and its distribution along with the branch of the formed tube in HCAECs, resulting in an increase in the number of tubes formed in HCAECs. ACh increased the levels of pAKT and phosphorylation of Sp1 in HCAECs, resulting in inducing SDF-1α expression, and the specific effects could be abolished by mecamylamine, atropine, the PI3K/AKT blocker wortmannin or the Sp1 blocker mithramycin. Functionally, VNS improved left ventricular performance, which could be abolished by Ad-shSDF-1α. VNS promoted angiogenesis to repair the infarcted heart by inducing SDF-1α expression and redistribution along new branches during angiogenesis, which was associated with the m/nAChR-AKT-Sp1 signalling pathway.

Increasing Incidence of ST-Elevation Acute Coronary Syndrome in Young South Asian Population, a Challenge for the World? An Assessment of Clinical and Angiographic Patterns and Hospital Course of Premature Acute Myocardial Infarction

The incidence of premature ischemic heart disease (IHD) is increasing because of urbanization, a sedentary lifestyle, and various other unexplored factors, especially in South Asia. This study aimed to assess the distribution of premature ST-elevation acute coronary syndrome (STE-ACS) with its clinical and angiographic pattern along with hospital course in a contemporary cohort of patients who underwent primary percutaneous intervention at a tertiary care center in the South Asian region. We included consecutive patients of either gender diagnosed with STE-ACS and who underwent primary percutaneous intervention. Patients were stratified based on age as ≤40years (young) and >40years (old). Clinical characteristics, angiographic patterns, and hospital course were compared between the 2 groups. Of the total of 4,686 patients, 466 (9.9%) were young (≤40years). Young patients had a lower prevalence of hypertension (40.8% vs 54.5%, p<0.001), diabetes (26.6% vs 36.4%, p<0.001), metabolic syndrome (14.8% vs 24%, p<0.001), history of IHD (5.8% vs 9.3%, p=0.013) and a higher frequency of smoking (33% vs 24.7%, p<0.001), positive family history (8.2% vs 3.2%, p<0.001), and single-vessel involvement (60.1% vs 33.2%, p<0.001). The composite adverse clinical outcome occurrence was significantly lower in young patients (14.2% vs 19.5%, p=0.006). On multivariable analysis, history of IHD in young, whereas age, Killip class III/IV, intubated, arrhythmias on arrival, diabetes, history of IHD, pre-procedure left ventricular end-diastolic pressure, ejection fraction <40%, and slow flow/no-reflow during the procedure were found to be the independent predictors of adverse clinical outcome in old patients. In conclusion, we have a substantial burden of premature STE-ACS, mostly in male patients potentially driven by smoking and positive family history. Despite favorable pathophysiology, with mostly single-vessel hospital courses of STE-ACS in the young equally lethal in nature.

Long-term inorganic nitrate administration protects against myocardial ischemia-reperfusion injury in female rats

BackgroundThe favorable effects of nitrate against myocardial ischemia-reperfusion injury (MIRI) have primarily focused on male rats and in short term. Here we determine the impact of long-term nitrate intervention on baseline cardiac function and the resistance to MIRI in female rats.MethodsFemale Wistar rats were randomly divided into untreated and nitrate-treated (100 mg/L sodium nitrate in drinking water for 9 months) groups (n = 14/group). At intervention end, levels of serum progesterone, nitric oxide metabolites (NOx), heart NOx concentration, and mRNA expressions of NO synthase isoforms (NOS), i.e., endothelial (eNOS), neuronal (nNOS), and inducible (iNOS), were measured. Isolated hearts were exposed to ischemia, and cardiac function indices (CFI) recorded. When the ischemia-reperfusion (IR) period ended, infarct size, NO metabolites, eNOS, nNOS, and iNOS expression were measured.ResultsNitrate-treated rats had higher serum progesterone (29.8%, P = 0.013), NOx (31.6%, P = 0.035), and higher heart NOx (60.2%, P = 0.067), nitrite (131%, P = 0.018), and eNOS expression (200%, P = 0.005). Nitrate had no significant effects on baseline CFI but it increased recovery of left ventricular developed pressure (LVDP, 19%, P = 0.020), peak rate of positive (+ dp/dt, 16%, P = 0.006) and negative (–dp/dt, 14%, P = 0.014) changes in left ventricular pressure and decreased left ventricular end-diastolic pressure (LVEDP, 17%, P < 0.001) and infarct size (34%, P < 0.001). After the IR, the two groups had significantly different heart nitrite, nitrate, NOx, and eNOS and iNOS mRNA expressions.ConclusionsLong-term nitrate intervention increased the resistance to MIRI in female rats; this was associated with increased heart eNOS expression and circulating progesterone before ischemia and blunting ischemia-induced increased iNOS and decreased eNOS after MIRI.

Acute hyperglycemia, a rabble-rouser or innocent bystander? A prospective analysis of clinical implications of acute hyperglycemia in STE-ACS patients

BackgroundAcute hyperglycemia is considered an independent prognosticator of both in-hospital and long-term outcomes in patients with acute coronary syndrome (ACS). This study aimed To analyze the incidence of acute hyperglycemia and its impact on the adverse in-hospital outcome in patients with STE-ACS undergoing primary percutaneous coronary intervention (PCI).MethodsIn this study, we enrolled patients presenting with STE-ACS and undergoing primary PCI at a tertiary care cardiac center. Acute hyperglycemia was defined as random plasma glucose (RBS) > 200 mg/dl at the time of presentation to the emergency room.ResultsOf the 4470 patients, 78.8% were males, and the mean age was 55.52 ± 11 years. In total, 39.4% (1759) were found to have acute hyperglycemia, and of these, 59% (1037) were already diagnosed with diabetes. Patients with acute hyperglycemia were observed to have a higher incidence of heart failure (8.2% vs. 5.5%; p < 0.001), contrast-induced nephropathy (10.9% vs. 7.4%; p < 0.001), and in-hospital mortality (5.7% vs. 2.5%; p < 0.001). On multivariable analysis, acute hyperglycemia was found to be an independent predictor of mortality with an adjusted odds ratio of 1.81 [1.28–2.55]. Multi-vessel disease (1.73 [1.17–2.56]), pre-procedure left ventricular end-diastolic pressure (LVEDP) (1.02 [1.0-1.03]), and Killip class III/IV (4.55 [3.09–6.71]) were found to be the additional independent predictors of in-hospital mortality.ConclusionsAcute hyperglycemia, regardless of diabetic status, is an independent predictor of in-hospital mortality among patients with STE-ACS undergoing primary PCI. Acute hyperglycemia, along with other significant predictors such as multi-vessel involvement, LVEDP, and Killip class III/IV, can be considered for the risk stratification of these patients.

Abstract P2010: Relationship between echocardiographic parameters and invasively measured left ventricular filling pressure in the persistent atrial fibrillation with preserved left ventricular systolic function

Background: Among patients with normal systolic function, elevated left ventricular end diastolic pressure (LVEDP) could represent early diastolic dysfunction or could be the main physiological consequence of diastolic dysfunction. However, the evaluation of LVEDP using classic echocardiographic assessment has been challenging in the setting of atrial fibrillation (AF). The aim of this study was to investigate the methods for predicting LVEPD in patients with persistent AF. Methods: Clinical data, laboratory data, and echocardiography findings were assessed in 90 patients with chronic AF who were undergoing diagnostic left-heart catheterization. LVEDP and standard echocardiographic measurements including pulmonary arterial systolic pressure (PASP) were evaluated. Results: E/e’ (r=0.448, p&lt;0.001), E/Vp (r=0.471, p&lt;0.001) and PASP (r=0.421, p&lt;0.001) correlated well with LVEDP (figure 1). Using receiver operating characteristic analysis, the optimal cut-off for E/e’ was 13 (sensitivity, 88%; specificity, 65%) to predict LVEDP of &gt;15 mmHg (figure ). Conclusion: E/e’, E/Vp and PASP were well correlated with LVEDP in patients with AF with preserved EF. E/e’ greater than 13 may suggest elevated LVEDP (&gt;15 mmHg) in patients with persistent AF.

Abstract P2159: Naltrindole Attenuates Phorbol 12-myristate 13-acetate Induced Superoxide Release In Polymorphonuclear Leukocytes Independently Of Delta Opioid Receptor Antagonism

Naltrindole (NTI) is a selective delta opioid receptor antagonist that recently has been shown to be cardioprotective in both in vivo and ex vivo studies. In vivo, NTI showed cardioprotective effects that were dose-dependent significantly reducing infarct size up to 82% compared to controls subjected to ischemia-reperfusion (I/R) injury (p&lt;0.05). In ex vivo isolated rat I/R hearts, NTI significantly reduced infarct size compared to controls (p&lt;0.01). NTI restored cardiac left ventricular end diastolic pressure to near baseline values compared to controls or other general opioid receptor antagonists in ex vivo hearts, suggesting a tissue salvaging mechanism independent of opioid delta receptor antagonism. Polymorphonuclear leukocytes (PMNs) do not express opioid receptors. In this study, we investigated NTI attenuation of PMN superoxide (SO) release in vitro . We hypothesized that NTI would attenuate PMN SO release via a calcium handling mechanism, a similar mechanism that explained cardioprotective effects of NTI pretreatment mitigating ischemic hypercontracture due to an increase in intracellular calcium. Rat PMNs (5x10 6 ) were incubated for 15 min at 37 o C in the presence or absence (dH 2 O vehicle controls) of NTI (10μM, 50μM, or 200μM). PMN SO release was calculated by the change in absorbance at 550 nm over 420 sec via ferricytochrome c reduction after phorbol 12-myristate-13 acetate (PMA) stimulation (100nM). Cell viability was determined microscopically by 0.2% trypan blue exclusion at the end of the assay. Data were analyzed using ANOVA Fisher’s PLSD post-hoc test. NTI significantly decreased PMN SO release from 30 sec to 420 sec. Changes in final absorbance of NTI 200μM (0.244±0.07, n=8, p&lt;0.05) and 50μM (0.293±0.06, n=4, p&lt;0.05), but not NTI 10μM (0.412±0.07, n=5), were significant compared to controls (0.487±0.12, n=9). Cell viability was not significantly different compared to PMA across all NTI concentrations. These results suggest that NTI reduces I/R injury and PMN SO release, by a means independent of delta opioid receptor antagonism. Future studies will assess NTI SO attenuation in human umbilical vein endothelial cells. We will use different concentrations to investigate optimal concentration response.

Abstract P2004: T Lymphocytes Promote Diastolic Dysfunction And Fibrosis In A Non-Hypertensive Angiotensin II Mouse Model Of Heart Failure

Background: Angiotensin (Ang) II signaling and diastolic dysfunction are hallmarks of heart failure (HF). Ang II promotes hypertension (HTN)-mediated cardiac fibrosis and remodeling as well as T lymphocyte activation during the pathogenesis of HF. We hypothesized that AngII induces HF, independent of HTN, through T cell activation in a mouse model. Methods: Using a non-HTN AngII model, we administered AngII (0.2 μg/kg/day) or H 2 O vehicle through subcutaneous pumps in wild type (WT) or T cell receptor α knockout ( Tcrα -/- ; bereft of T cells) mice (15 wks old, N=5-7/group). We used flow cytometry to detect T cells (CD45+CD3+) in LV single-cell suspensions. LV dimensions, ejection fraction (EF), and diastolic function (isovolumetric relaxation time - IRT) were measured after 4 wks with Doppler echocardiography. LV end-diastolic pressure (EDP) was measured with a Millar catheter. Heart slides were stained with picrosirius red to measure interstitial fibrosis. Results: T cells were significantly increased in the LV by AngII vs H 2 O (23.0±2.1% vs 9.4±1.7%, p&lt;0.001). All groups had similar LV dimensions and EF (not shown). AngII increased IRT (15.1±1.0 vs 8.6±0.6 ms, p&lt;0.0001) and LVEDP (9.0±1.3 vs 3.2±0.5 mmHg, p&lt;0.001) in WT mice vs H 2 O, but did not increase IRT and LVEDP in Tcrα-/- mice (11.8±0.8 vs 9.5±0.8 ms and 3.2±0.8 vs 2.9±0.5 mmHg; all p=ns), which were significantly lower than that of WT mice (all p&lt;0.05). AngII increased interstitial fibrosis in WT mice (2.2±0.2 vs 0.7±0.1%, p&lt;0.0001) while Tcrα-/- hearts had significantly less fibrosis (1.0±0.1%, p&lt;0.001). Conclusions: T cells are increased in the LV and promote diastolic dysfunction and fibrosis in a non-HTN AngII HF mouse model.

Abstract P3077: Withdrawal Of High Fat Diet And L-NAME Dampens T Cell Activation And Ameliorates Pathology In Experimental Heart Failure With Preserved Ejection Fraction (HFPEF) Through Modulation Of The T Cell IRE1a-XBP1 Axis

Introduction: Cardiometabolic HFpEF is characterized by T cell systemic inflammation and can be modeled preclinically with high fat diet (HFD) and L-NAME. Metabolic perturbations can alter T cell function through modulation of the unfolded protein response (UPR). How T cells are activated in HFpEF and whether T cell inflammation can be tuned by removing cardiometabolic stress remains unknown. Hypothesis: HFD and L-NAME induce reversible alterations in T cell UPR signaling that modulate T cell dependent cardiac inflammation and pathology in experimental HFpEF. Methods: Male C57/BL6J mice (wild-type, WT), OT-II antigen restricted mice, and CD4 Cre Xbp1 fl/fl mice were fed a high-fat diet (HFD) and L-NAME (H/L) for 5 weeks. WT mice were switched to standard diet (STD) for two additional weeks. WT mice receiving HFD or L-NAME only, or TAC surgery (a model of HF with reduced EF) were used as controls. Left ventricular (LV) end diastolic pressure volume relationship (EDPVR) was assessed using invasive hemodynamic analyses and LV EF by echocardiography. Cardiac and splenic T cells were characterized by flow cytometry and T cell UPR was evaluated by qPCR and Western blot. Results: 5 weeks of H/L was sufficient to induce cardiac T cell infiltration and splenic T cell activation. OTII mice fed H/L showed increased cardiac CD4 + T cell infiltration compared to STD controls, indicating T cell activation is not cardiac antigen restricted. Furthermore, splenic T cell characterization revealed H/L resulted in decreased phosphorylation of the UPR protein inositol-requiring enzyme 1α (IRE1α) and reduced expression of X box-binding protein 1 ( Xbp1s/u ) compared to T cells from mice exposed to HFD or L-NAME alone, STD, or WT TAC controls. CD4 Cre+ Xbp1 fl/fl mice (T cell Xbp1 -/- ) fed with H/L had increased cardiac T cell infiltration compared to Cre - controls. Lastly, Xbp1s expression in splenic CD4 + T cells was recovered after withdrawal of H/L and resulted in partial reduction of cardiac hypertrophy, decreased EDPVR, as well as less cardiac T cell infiltration compared to mice kept on H/L. Conclusions: Reversible downregulation of the T cell IRE1α-XBP1 axis is a unique T cell signature of HFpEF that contributes to T cell inflammation and adverse cardiac remodeling.

Abstract P3103: Heart Failure In Menopause: Treatment With Rock Inhibitor And Atorvastatin

In advanced age, women tend to develop heart failure with preserved ejection fraction (HFpEF) due to estrogen depletion. The signaling pathway of ROCK is involved in cardiac complications consequent to female aging. Thus, this work investigated the comparative effects of atorvastatin and ROCK inhibitor, fasudil on the treatment of HFpEF induced by oophorectomy (OVX) in spontaneously hypertensive rats (SHR). Protocols were approved by the Animal Care and Use Committee at Universidade Federal do Rio de Janeiro. Under anesthesia with ketamine (80 mg/kg, i.p.) and xylazine (15 mg/kg, i.p.), female SHR were submitted to OVX procedure and after 8 wks were randomly orally treated with either vehicle or atorvastatin (40 mg/kg) or fasudil (10 mg/kg) during 4 wks. At the end of treatment, hemodynamic parameters were evaluated using echocardiography and LV catheterization. Cardiac tissues were collected for histologic analysis. Cardiac hypertrophy was reversed by treatment with atorvastatin or fasudil. Increased systolic pressure of LV was observed in SHR-OVX group (149.2 ± 7.9 mmHg), which was partially reduced by fasudil (123.4 ± 7.4 mmHg) and normalized by atorvastatin (94.5 ± 3.9 mmHg). Reduction of the increased diastolic dysfunction observed by echocardiogram was confirmed, since the recovery of the increased LV end diastolic pressure of SHR-OVX (32.1 ± 1.8 mmHg) occurred after treatment with atorvastatin (22.4 ± 9.6 mmHg) and fasudil (11.9 ± 2.4 mmHg). Fibrosis was observed because of the increased collagen deposition in SHR-OVX (6.2 ± 0.1%), with partial reduction with fasudil (4.4 ± 0.3%) and normalization after treatment with atorvastatin (1.9 ± 0.7%). Cell proliferation was evaluated using the p38 marker, where the percentage of nuclei marked was determined in relation to the total, through immunohistochemical technique. An increase in nuclear p38 in the SHR-OVX group was observed (23.2 ± 3.2%), however, the treatment with atorvastatin (12.1 ± 1.7%) and fasudil (5.3 ± 1.3%) reduced the nuclear p38 detection. In conclusion, atorvastatin and fasudil promoted recovery of HFpEF induced by estrogen depletion in SHR. Inhibition of ROCK signalling by atorvastatin could be involved in the reduction of diastolic dysfunction observed in OVX-SHR group.

Association Between Coronary Flow Reserve and Left Ventricular End Diastolic Pressure

Association Between Coronary Flow Reserve and Left Ventricular End Diastolic Pressure

Pediatric restrictive cardiomyopathy: a case report.

Restrictive cardiomyopathy (RCM) is a rare childhood cardiomyopathy that is a challenging diagnostic problem for clinicians. We describe a case of an 8-year-old girl with a 2-year history of shortness of breath on exertion. Electrocardiogram and echocardiography showed biatrial enlargement, while cardiac magnetic resonance showed biatrial dilation and normal pericardial thickness. Left and right heart catheterization revealed a left ventricular (LV) end-diastolic pressure (EDP) of 20 mmHg, right ventricular (RV) EDP of 13 mmHg, and pulmonary arterial systolic pressure of 51 mmHg. LV and RV pressure traces showed that LV and RV pressures moved concordantly with respiration, and that the systolic area index was 0.98. Cardiac catheterization data were therefore supportive of RCM. Next-generation sequencing identified a heterozygous variant of the troponin I gene (TNNI3; c.574C>T). Combining these findings led to a diagnosis of RCM. The patient's parents chose conservative treatment, but at the 12-month follow-up she died of worsening heart failure and cerebral infarction. This case emphasizes the need for cardiac catheterization and genetic testing in RCM, and suggests that anticoagulants should be recommended to reduce the risk of thromboembolic events.

Changing haemodynamic status of patients referred for transcatheter aortic valve intervention during the COVID-19 pandemic.

Delays in the diagnosis and referral of aortic stenosis (AS) during the coronavirus disease 2019 (COVID-19) pandemic may have affected the haemodynamic status of AS patients. We aimed to compare clinical and haemodynamic characteristics of severe AS patients referred for transcatheter aortic valve implantation (TAVI) or balloon aortic valvuloplasty (BAV) before the pandemic versus two subsequent periods. This study compared three 1‑year historical cohorts: apre-COVID-19 group (PCOV), a1st-year COVID-19 group (COV-Y1) and a2nd-year COVID-19 group (COV-Y2). The main parameters were baseline New York Heart Association (NYHA) functional class, left ventricular ejection fraction (LVEF) and left ventricular end-diastolic pressure (LVEDP). Demographics, procedural characteristics and 30-day clinical outcomes were assessed. The transition time between heart team decision and TAVI was examined. Pairwise group comparisons were performed (PCOV vs COV-1Y and COV-1Y vs COV-2Y). Atotal of 720patients were included with 266, 249 and 205patients in the PCOV, COV-Y1 and COV-Y2groups, respectively. BAV was performed in 28patients (4%). NYHA class did not differ across the cohorts. Compared to PCOV, LVEF was slightly lower in COV-Y1 (58% (49-60%) vs 57% (45-60%), p = 0.03); no difference was observed when comparing COV-Y1 and COV-Y2. LVEDP was higher in COV-Y1 than in PCOV (20 mm Hg (16-26 mm Hg) vs 17 mm Hg (13-24 mm Hg), p = 0.01). No difference was found when comparing LVEDP between COV-Y1 and COV-Y2. Thirty-day mortality did not differ between groups. Transition time was reduced in the COVID era. Duration of hospital stay declined over the study period. Patients undergoing TAVI during the COVID-19 pandemic had more advanced AS illustrated by lower LVEF and higher LVEDP, but there were no differences in clinical outcome. The TAVI pathway became more efficient.

Left Ventricular End-Diastolic Pressure for the Prediction of Contrast-Induced Nephropathy and Clinical Outcomes in Patients With ST-Elevation Myocardial Infarction Who Underwent Primary Percutaneous Intervention (the ELEVATE Study)

Contrast-induced nephropathy (CIN) is an important complication of percutaneous coronary intervention (PCI). We investigated whether left ventricular end-diastolic pressure (LVEDP) in patients who underwent PCI might be additive to current risk stratification of CIN. Data from consecutive patients who underwent primary PCI for ST-elevation myocardial infarction between 2013 and 2018 at Western Health in Victoria, Australia were analyzed. CIN was defined as a 25% increase in serum creatinine from baseline or 44 µmol/L increase in absolute value within 48 hours of contrast administration. Compared with patients without CIN (n=455, 93%), those who developed CIN (n=35, 7%) were older (64 vs 58 years, p=0.006), and had higher peak creatine kinase (2,862 [1,258 to 3,952] vs 1,341 U/L [641 to 2,613], p=0.02). The CIN group had higher median LVEDP (30 [21-33] vs 25 mmHg [20-30], p=0.013) and higher median Mehran risk score (MRS) (5 [2-8] vs 2 [1-5], p<0.001). Patients with CIN had more in-hospital major adverse cardiovascular and cerebrovascular events (composite end point of death, new or recurrent myocardial infarction or stent thrombosis, target vessel revascularization or stroke) (23% vs 8.6%, p=0.01), but similar 30-day major adverse cardiovascular and cerebrovascular events (20% vs 15%, p=0.46). An LVEDP >30 mmHg independently predicted CIN (odds ratio 3.4, 95% confidence interval 1.46 to 8.03, p=0.005). The addition of LVEDP ≥30 mmHg to MRS marginally improved risk prediction for CIN compared with MRS alone (area-under-curve, c-statistic=0.71 vs c-statistic=0.63, p=0.08). In conclusion, elevated LVEDP ≥30 mmHg during primary PCI was an independent predictor of CIN in patients treated for ST-elevation myocardial infarction. The addition of LVEDP to the MRS may improve risk prediction for CIN.

Effects of pre-electroacupuncture on blood pressure and cardiac function in high-salt-induced hypertension rats

To observe the effects of pre-electroacupuncture at "Taichong"(LR3), "Neiguan"(PC6) and "Waiguan"(TE5) on blood pressure and cardiac function of high-salt-induced hypertension rats, so as to explore the possible mechanism of pre-electroacupuncture in improving hypertension. Twenty-four SD rats were randomly divided into control group, high-salt group and pre-electroacupuncture group, with 8 rats in each group. The hypertension model was established by feeding high-salt diet for 7 weeks. In the pre-electroacupuncture group, rats received electroacupuncture intervention at bilate-ral LR3, PC6 and TE5 (2 Hz/15 Hz, 2 mA) for 30 min, once a day, from the first day of modeling, for a total of 7 weeks. The blood pressure of rats was monitored by caudal artery noninvasive blood pressure measurement technique before and at the 1st, 3rd, 5th and 7th week of modeling. At the 8th week of the experiment, left ventricular catheterization was performed and biological signal acquisition system was used to detect left ventricular hemodynamics indexes and analyze left ventricular function, the car-diac mass ratio was measured to evaluate the degree of myocardial hypertrophy. The mRNA expressions of atrial natriuretic peptide(ANP), myosin heavy chain 7(MYH7), α-smooth muscle actin(α-SMA), interleukin(IL)-1β, and IL-6 of myocardial tissues were detected by quantitative real-time PCR. Sirius red staining was used to observe the degree of myocardial fibrosis. Compared with the control group, systolic blood pressure, diastolic blood pressure, mean arterial pressure, left ventricular end-diastolic pressure (LVEDP), cardiac mass ratio，and the mRNA expressions of ANP, MYH7, α-SMA, IL-1β, and IL-6, and sirius red staining area of myocardium were all significantly increased(P<0.01,P<0.05)，maximal rate of rise and descent of left ventricular pressure(LVP±dP/dtmax) were decreased (P<0.05,P<0.01) in the high-salt group. Compared with the high-salt group, rats in the pre-electroacupuncture group had lower systolic blood pressure, diastolic blood pressure, mean arterial pressure, LVEDP，cardiac mass ratio，higher LVP±dP/dtmax,down-regulated mRNA expressions of ANP, MYH7, α-SMA, IL-1β, IL-6, and smaller area of sirius red staining(P<0.05, P<0.01). Pre-electroacupuncture tends to lower blood pressure, improve cardiac function and reduce myocardial fibrosis in high-salt-induced hypertension rats, which may be associated with inhibiting inflammatory response.