Left Ventricular End-diastolic Pressure Research Articles

Influence of carvedilol and thyroid hormones on inflammatory proteins and cardioprotective factor HIF-1α in the infarcted heart

Inflammatory pathways of Toll-like receptor 4 (TLR4) and NLRP3 inflammasome contribute to acute myocardial infarction (AMI) pathophysiology. The hypoxia-inducible factor 1α (HIF-1α), however, is a key transcription factor related to cardioprotection. This study aimed to compare the influence of carvedilol and thyroid hormones (TH) on inflammatory and HIF-1α proteins and on cardiac haemodynamics in the infarcted heart. Male Wistar rats were allocated into five groups: sham-operated group (SHAM), infarcted group (MI), infarcted treated with the carvedilol group (MI+C), infarcted treated with the TH group (MI+TH), and infarcted co-treated with the carvedilol and TH group (MI+C+TH). Haemodynamic analysis was assessed 15 days post-AMI. The left ventricle (LV) was collected for morphometric and Western blot analysis. The MI group presented LV systolic pressure reduction, LV end-diastolic pressure elevation, and contractility index decrease compared to the SHAM group. The MI+C, MI+TH, and MI+C+TH groups did not reveal such alterations compared to the SHAM group. The MI+TH and MI+C+TH groups presented reduced MyD88 and NLRP3 and increased HIF-1α levels. In conclusion, all treatments preserve the cardiac haemodynamic, and only TH, as isolated treatment or in co-treatment with carvedilol, was able to reduce MyD88 and NLRP3 and increase HIF-1α in the infarcted heart.

Diagnostic value of parameters derived from planar MUGA for detecting HFpEF in coronary artery disease patients

BackgroundIn recent years, heart failure with preserved ejection fraction (HFpEF) has received increasing clinical attention. To investigate the diagnostic value of diastolic function parameters derived from planar gated blood-pool imaging (MUGA) for detecting HFpEF in coronary atherosclerotic heart disease (coronary artery disease, CAD) patients.MethodsNinety-seven CAD patients with left ventricular ejection fraction ≥ 50% were included in the study. Based on the left ventricular end-diastolic pressure (LVEDP), the patients were divided into the HFpEF group (LVEDP ≥ 16 mmHg, 47 cases) and the normal LV diastolic function group (LVEDP < 16 mmHg, 50 cases). Diastolic function parameters obtained by planar MUGA include peak filling rate (PFR), filling fraction during the first third of diastole (1/3FF), filling rate during the first third of diastole (1/3FR), mean filling rate during diastole (MFR), and peak filling time (TPF). Echocardiographic parameters include left atrial volume index (LAVI), peak tricuspid regurgitation velocity (peak TR velocity), transmitral diastolic early peak inflow velocity (E), average early diastolic velocities of mitral annulars (average e′), average E/e′ ratio. The diastolic function parameters obtained by planar MUGA were compared with those obtained by echocardiography to explore the clinical value of planar MUGA for detecting HFpEF.ResultsThe Receiver-operating characteristic curve analysis of diastolic function parameters obtained from planar MUGA and echocardiography to detect HFpEF showed that: among the parameters examined by planar MUGA, the area under the curve (AUC) of PFR, 1/3FF, 1/3FR, MFR and TPF were 0.827, 0.662, 0.653, 0.663 and 0.809, respectively. Among the echocardiographic parameters, the AUCs for average e′, average E/e′ ratio, peak TR velocity, and LAVI values were 0.747, 0.706, 0.735, and 0.633. The combination of PFR and TPF showed an AUC of 0.856. PFR combined with TPF value demonstrated better predictive value than average e′ (Z = 2.020, P = 0.043).ConclusionDiastolic function parameters obtained by planar MUGA can be used to diagnose HFpEF in CAD patients. PFR combined with TPF was superior to the parameters obtained by echocardiography and showed good sensitivity and predictive power for detecting HFpEF.

Overlapping and Distinct Features of Cardiac Pathology in Inherited Human and Murine Ether Lipid Deficiency.

Inherited deficiency in ether lipids, a subgroup of glycerophospholipids with unique biochemical and biophysical properties, evokes severe symptoms in humans resulting in a multi-organ syndrome. Mouse models with defects in ether lipid biosynthesis have widely been used to understand the pathophysiology of human disease and to study the roles of ether lipids in various cell types and tissues. However, little is known about the function of these lipids in cardiac tissue. Previous studies included case reports of cardiac defects in ether-lipid-deficient patients, but a systematic analysis of the impact of ether lipid deficiency on the mammalian heart is still missing. Here, we utilize a mouse model of complete ether lipid deficiency (Gnpat KO) to accomplish this task. Similar to a subgroup of human patients with rhizomelic chondrodysplasia punctata (RCDP), a fraction of Gnpat KO fetuses present with defects in ventricular septation, presumably evoked by a developmental delay. We did not detect any signs of cardiomyopathy but identified increased left ventricular end-systolic and end-diastolic pressure in middle-aged ether-lipid-deficient mice. By comprehensive electrocardiographic characterization, we consistently found reduced ventricular conduction velocity, as indicated by a prolonged QRS complex, as well as increased QRS and QT dispersion in the Gnpat KO group. Furthermore, a shift of the Wenckebach point to longer cycle lengths indicated depressed atrioventricular nodal function. To complement our findings in mice, we analyzed medical records and performed electrocardiography in ether-lipid-deficient human patients, which, in contrast to the murine phenotype, indicated a trend towards shortened QT intervals. Taken together, our findings demonstrate that the cardiac phenotype upon ether lipid deficiency is highly heterogeneous, and although the manifestations in the mouse model only partially match the abnormalities in human patients, the results add to our understanding of the physiological role of ether lipids and emphasize their importance for proper cardiac development and function.

Prognostic Implications of Left Atrial Stiffness Index in Heart Failure Patients With Preserved Ejection Fraction

BackgroundThe left atrium (LA) plays an important role in the pathophysiology and disease progression of heart failure with preserved ejection fraction (HFpEF). ObjectivesThis study sought to assess the prognostic potential of LA stiffness index in patients who have HFpEF. MethodsThis study retrospectively screened patients with elevated left ventricular end-diastolic pressure (≥16 mm Hg) and preserved ejection fraction (≥50%) between January 1, 2004, and December 31, 2019. All patients underwent left heart catheterization to measure left ventricular end-diastolic pressure. Among these, 307 patients who had suitable image quality for left peak atrial longitudinal strain (PALS) measurement were analyzed. The study population was classified into low LA stiffness (n = 178, early diastolic transmitral inflow velocity/mitral annulus early diastolic velocity [E/e′]/PALS ≤0.26) and high LA stiffness (n = 129, E/e′/PALS >0.26) according to the best LA stiffness index (E/e′/PALS) cutoff value. The primary outcome was a composite of mortality or hospitalization caused by heart failure during follow-up. ResultsLA stiffness index showed good correlations with E/e′ (r = 0.737; P < 0.001), LA volume index (r = 0.529; P < 0.001), right ventricular systolic pressure (r = 0.404; P < 0.001), and log N-terminal pro–B-type natriuretic peptide (r = 0.540; P < 0.001). LA stiffness index demonstrated better predictive performance than echocardiographic diastolic parameters did (P < 0.001). Patients with low LA stiffness had better clinical outcomes than those with high LA stiffness during a median follow-up of 6 years did (P < 0.001). In multivariable analysis, LA stiffness index was independently associated with increased risk of the composite endpoint of death or heart failure hospitalization (HR: 1.59 [95% CI: 1.01-2.51]; P = 0.044). ConclusionsIncreased LA stiffness was associated with increased risk for all-cause mortality and hospitalization caused by heart failure in patients who have HFpEF, and its prognostic role was more pronounced than that of indexes of left ventricular filling pressure.

Can volume-reduced plasma products prevent transfusion-associated circulatory overload in a two-hit animal model?

Transfusion-associated circulatory overload (TACO) is a pulmonary transfusion complication and a leading cause of transfusion-related morbidity and mortality. Volume overload and rising hydrostatic pressure as a consequence of transfusion are seen as the central pathway leading to TACO. A possible preventative measure for TACO could be the use of low-volume blood products like volume-reduced lyophilized plasma. We hypothesize that volume-reduced lyophilized plasma decreases circulatory overload leading to a reduced pulmonary capillary pressure and can therefore be an effective strategy to prevent TACO. A validated two-hit animal model in rats with heart failure was used. Animals were randomized to receive 4 units of either solvent-detergent pooled plasma (SDP) as control, standard volume lyophilized plasma (LP-S) or hyperoncotic volume-reduced lyophilized plasma (LP-VR). The primary outcome was the difference between pre-transfusion and post-transfusion left ventricular end-diastolic pressure (ΔLVEDP). Secondary outcomes included markers for acute lung injury. LVEDP increased in all randomization groups following transfusion. The greatest elevation was seen in the group receiving LP-VR (+11.9 mmHg [5.9-15.6]), but there were no significant differences when compared to groups receiving either LP-S (+6.3 mmHg [2.9-13.4], p=0.29) or SDP (+7.7 mmHg [4.5-10.5], p=0.55). There were no significant differences in markers for acute lung injury, such as pulmonary wet/dry weight ratios, lung histopathology scores or PaO2 /FiO2 ratio between the three groups. Transfusion with hyperoncotic volume-reduced plasma did not attenuate circulatory overload compared to standard volume plasma and was therefore not an effective preventative strategy for TACO in this rat model.

Mechanical Assist Device-Assisted Percutaneous Coronary Intervention: The Use of Impella Versus Extracorporeal Membrane Oxygenation as an Emerging Frontier in Revascularization in Cardiogenic Shock.

The extracorporeal membrane oxygenation (ECMO) procedure aids in the provision of prolonged cardiopulmonary support, whereas the Impella device (Abiomed, Danvers, MA) is a ventricular assist device that maintains circulation by pumping blood into the aorta from the left ventricle. Blood is circulated in parallel with the heart by Impella. It draws blood straight into the aorta from the left ventricle, hence preserving the physiological flow. ECMO bypasses the left atrium and the left ventricle, and the end consequence is a non-physiological flow. In this article, we conducted a detailed analysis of various publications in the literatureand examined various modalities pertaining to the use ofECMO and Impella for cardiogenic shocks, such as efficacy, clinical outcomes, cost-effectiveness, device-related complications, and limitations. The Impella completely unloads the left ventricle, thereby significantly reducing the effort of the heart. Comparatively, ECMO only stabilizes a patient with cardiogenic shock for a short stretch of time and does not lessen the efforts of the left ventricle ("unload" it). In the acute setting, both devices reduced left ventricular end-diastolic pressure and provided adequate hemodynamic support. By comparing patients on Impella to those receiving ECMO, it was found that patients on Impella were associated with better clinical results, quicker recovery, limited complications, and reduced healthcare costs; however, there is a lack of conclusive studies performed demonstrating the reduction in long-term mortality rates. Considering the effectiveness of given modalities and taking into account the various studies described in the literature, Impella has reported better clinical outcomes although more clinical trials are needed for establishing the effectiveness of these interventional approaches in revascularization in cardiogenic shock.

Oxymatrine ameliorates myocardial injury by inhibiting oxidative stress and apoptosis via the Nrf2/HO-1 and JAK/STAT pathways in type 2 diabetic rats

The necessity of increasing the efficiency of organ preservation has encouraged researchers to explore the mechanisms underlying diabetes-related myocardial injuries. This study intended to evaluate the protective effects of oxymatrine (OMT) in myocardial injury caused by type 2 diabetes mellitus. A model of diabetic rats was established to simulate type 2 diabetes mellitus using an intraperitoneal injection of a single dose of 65 mg/kg streptozotocin with a high-fat and high-cholesterol diet, and diabetic rats were subsequently treated with OMT (60, 120 mg/kg) by gavage for 8 weeks. Thereafter, diabetic rats demonstrated notable decreases in left ventricular systolic pressure (LVSP), ±dp/dtmax, and in the activities of glutathione peroxidase, superoxide dismutase, and catalase. Moreover, we found notable increases in left ventricular end-diastolic pressure, fasting blood glucose, and malondialdehyde, as well as changes in cell apoptosis and decreased expression levels of Nrf2, HO-1, tyrosine protein kinase JAK (JAK), and signal transducer and transcription activator (STAT). Treatment with OMT alleviated all of the measured parameters. Collectively, these findings suggest that activation of the Nrf2/HO-1 and inhibition of the JAK/STAT signaling are involved in mediating the cardioprotective effects of OMT and also highlight the benefits of OMT in ameliorating myocardial injury in diabetic rats.

Improvement in LV end-diastolic pressure after primary PCI and its impact on patients' recovery.

In this study, we evaluated the change in left ventricular end-diastolic pressure (LVEDP) after primary percutaneous coronary intervention (PCI) and its impact on in-hospital outcomes and 30-day and three-month quality of life (SAQ-7), ejection fraction (EF), and major adverse cardiovascular events (MACE). LVEDP ≥19 mmHg was taken as elevated LVEDP. In a sample of 318 patients, 18.9% (n=60) were females and mean age was 55.7 ± 10.52 years. Post-procedure elevated LVEDP was observed in 20.8% (n=66) with a mean reduction of 1.65 ± 4.35 mmHg. LVEDP declined in 39% (n=124) and increased in 10.7% (n=34). In-hospital mortality rate (9.1% vs. 2.4%, p=0.011), 30-day MACE (9.1% vs. 4.0%), and three-month MACE (21.2% vs. 5.6%) were found to be significantly higher among patients with elevated LVEDP, respectively. Elevated LVEDP was found to be associated with a reduced SAQ-7 score (89.84 ± 8.09 vs. 92.29 ± 3.03, p<0.001) and reduced (25-40%) EF (55.6% vs. 22.6%) at three-month follow-up. LVEDP declined acutely in a significant number of patients after primary PCI. Post- procedure elevated LVEDP was found to be associated with poor quality of life and an increased risk of immediate and short-term MACE.

Transient Increase in the Terminal Negative Deflection of the P Wave in Lead V1 during Treadmill Testing Identifies Exercise Induced Aggravated Left Ventricular Dysfunction

Terminal negative deflection of the P wave in lead V1 is produced by posteriorly directed depolarization of the left atrium. A value of more than 0.04 mm sec suggests increase in left atrial pressure. Transient new appearance of this finding during treadmill testing suggests transient exercise induced increase in left atrial pressure. Indirectly it suggests transient exercise induced/aggravated increase in left ventricular end diastolic pressure. In presence of clinical and/or electrocardiographic findings of myocardial ischemia, this finding suggest ischemia induced left ventricular dysfunction. Earlier this finding appears during exercise and longer it lasts during recovery, more severe is the left ventricular dysfunction.

A total closed chest swine model of acute myocardial infarction-related cardiogenic shock: A critical double coronary sub-occlusion approach

The management of acute myocardial infarction-related cardiogenic shock (AMICS) represents a significant challenge, with mortality rates remaining high (40–60%), despite recent advances. Current animal models of myocardial infarction are either associated with a very high rate of per-procedure malignant arrhythmia, or with very low impairment of hemodynamic parameters, or with the inability to have complete coronary reperfusion. We sought to develop a closed chest and clinically relevant large animal model of severe AMICS, with high survival rate. Adult pigs were anaesthetized and mechanically ventilated. Percutaneous cardiac catheterization was performed under fluoroscopy. Advanced left ventricular dysfunction was induced by 120 minutes of critical sub-occlusion of the proximal left anterior descending coronary artery and the mid circumflex artery. A thorough hemodynamic assessment was obtained by invasive and non-invasive monitoring devices. Repeated blood samples were obtained to determine blood gas parameters, lactate, and haemoglobin concentration. After death, the heart was retrieved for further histological analyses. All animals (n = 12) developed significant circulatory failure associated with AMICS upon reperfusion and beyond. No animal died during the ischemia process. However, all animals that did not benefited from vasopressor support (“sham” group, n = 4) spontaneously died within 30 minutes of reperfusion, confirming the severity of the model. Cardiogenic shock was characterized by a drop in mean arterial pressure below 60 mmHg (58 ± 5 mmHg at 120 min of ischemia), a significant decrease in mean cardiac output (−44% from 5.7 ± 0.4 at baseline to 3.2 ± 0.4 at 120 minutes of ischemia) and SvO2 (−32% from 57 ± 8 at baseline to 39 ± 6 at 120 minutes of ischemia) and a significant increase in left ventricle end-diastolic pressure (LVEDP) (+110% from 10 ± 3 at baseline to 21 ± 3 at 120 minutes of ischemia). CO2 gap and coronary sinus venous oxygen saturation increased significantly upon ischemia and reperfusion and remained elevated throughout (P ≤ 0.001 for all comparisons). Myocardial samples corroborated extensive cellular necrosis and inflammatory infiltrates. We present, for the first time, a stable and clinically relevant model of severe AMICS obtained by critical double coronary sub-occlusion. The greater severity of the model did not lead to an increase in the frequency of malignant arrythmias and per-procedure mortality.

126: A CASE REPORT OF ELECTRICAL STORM POST-COVID-19 VACCINATION

Introduction: Post-vaccination arrhythmia is reported as a possible cardiovascular side effect of COVID-19 vaccination. We present a case of ventricular tachycardia (VT) storm in a young healthy man following the 2nd dose of COVID-19 vaccination in the absence of underlying structural heart disease, myocarditis or arrhythmic syndromes. Description: A 38-year-old male with no medical history was admitted after an out-of-hospital cardiac arrest and found to be in VT storm within 24 hours of receiving his 2nd dose of COVID-19 vaccination. He received 4 shocks en route and had another episode of pulseless VT on arrival where Amiodarone was initiated. Laboratory values showed elevated inflammatory markers, and COVID tests were negative. Troponin peaked at 1.5 ng/ml. Initial transthoracic echocardiogram (TTE) revealed normal left ventricular ejection fraction (LVEF) without regional wall motion abnormality. On Day 2, he developed VT storm and was given magnesium sulfate, lidocaine and an additional bolus of amiodarone. Repeat TTE revealed a significant decrease in EF. He became hypotensive requiring inotropes and was emergently taken to the cath lab where intra-aortic balloon pump (IABP) and temporary transvenous pacing (TVP) were placed. Cardiac catheterization revealed normal coronary arteries, elevated left ventricular end diastolic pressure and mildly dilated LV with global hypokinesis and EF of 30%. His condition slowly improved without further occurrences of VT storm. Follow up TTE revealed normal LVEF, IABP and TVP were removed, and he was extubated. Cardiovascular magnetic resonance imaging showed no evidence of myocarditis with normal LV size. An automatic implantable cardioverter-defibrillator was placed. Genetic testing for Brugada syndrome was negative. Discussion: VT storm typically occurs with underlying structural heart disease, inherited arrhythmic syndromes or myocarditis, and is often difficult to identify a specific trigger. Although this is the first case report of VT storm occurring after the COVID-19 vaccine, it is important to note that the lack of a definitive test to diagnose myocarditis such as biopsy is a major limiting factor. This case report also supports the need for structured studies regarding a possible relationship between VT storm and COVID-19 vaccination.

752 CARDIOGENIC SHOCK AS THE FIRST PRESENTATION OF ACUTE ANTRACYCLINE CARDIOTOXICITY: A CLINICAL CASE

Abstract Background Several therapeutic strategies are available for cancer patients, leading to a longer life expectancy; however, each drug might have different side effects, which increase morbidity and mortality. Cardiovascular diseases are one of the most frequent and dramatic of these side effects, leading to interruption of a potentially lifesaving treatment or hesitating into heart failure. Clinical Case A 50 year-old female with recent diagnosis of breast cancer presented to our Emergency Department (ED) for asthenia, vomiting and dyspnea. A first dose of epirubicin and cyclophosphamide as neoadjuvant chemotherapy (CT) was administered three days before the onset of symptoms. Screening echocardiogram performed before starting the CT showed normal systolic ejection fraction, normal diastolic function and no valvular disease. At ED admission, the patient presented hypotension, tachycardia, sweating and mental confusion. The ECG showed sinus tachycardia with diffuse ST segment elevation and diffuse low QRS voltages. Echocardiogram proved severe left dysfunction (LVEF 15%) with low cardiac output (LVOT VTI 6 mm) and elevated ventricular filling pressure (E/e’ 26). EAB showed severe hyperlactacidemia. The diagnosis of cardiogenic shock was done and high doses of dobutamine and noradrenaline were started. Laboratory values confirmed multiorgan involvement, in absence of any signs of inflammation and infection. The coronary angiography performed revealed normal coronary arteries and elevated left ventricular end-diastolic pressure (LVEDP 29 mmHg). Despite pharmacological therapy, the patient's condition worsened so we proceeded to IMPELLA CP implantation and started methylprednisolone 10 mg/kg for three days with subsequent tapering doses. After 24 hours, we obtained hemodynamic stability and hyperlactacidemia clearance. Unfortunately, myelotoxicity and marked piastrinopenia (until 16 000*10 9/L) complicated the clinical course; for this reason, we stopped unfractionated Heparin (UHF) and no anticoagulant therapy, other the one in purge solution, was performed. CMR revealed diffuse signal enhancement during the T2w sequences associated with a global enhancement of T2 Mapping values due to general edema, a global intramyocardial strengthening, a significant enhancement of the T1 mapping values and extracellular volume were described at the delayed enhancement sequences. The hemodynamic conditions progressively improved during the hospitalization and the IMPELLA pump was removed. Serial echocardiograms documented an improvement of the ejection fraction and further mild reduction of ventricular filling pressure (E/e’ 8) normal right ejection fraction and initial inferior vena cava collapsibility. All the inotropic supports were suspended; we introduced beta-blocker, ACE-inhibitors, subsequently replaced with sacubitril/valsartan, well tolerated. Conclusion Acute cardiotoxicity with possible life-threatening conditions regardless of the basal cardiovascular risk class is a rare clinical condition, but needs further investigation. Future researches are warranted to determine the molecular mechanisms underlying cardiotoxicity to contain the side effects, maximize the benefit of the oncological therapy and, when necessary, select the best therapeutic option.

Class of hemorrhagic shock is associated with progressive diastolic coronary flow reversal and diminished left ventricular function.

Introduction: The relationship between coronary artery flow and left ventricular (LV) function during hemorrhagic shock remains unknown. The aim of this study was to quantify coronary artery flow directionality alongside left ventricular function through the four classes of hemorrhage shock. Methods: Following baseline data collection, swine were exsanguinated into cardiac arrest via the femoral artery using a logarithmic bleed, taking each animal through the four classes of hemorrhagic shock based on percent bleed (class I: 15%; class II: 15%-30%; class III: 30%-40%; class IV: >40%). Telemetry data, left ventricular pressure-volume loops, and left anterior descending artery flow tracings over numerous cardiac cycles were collected and analyzed for each animal throughout. Results: Five male swine (mean 72 ± 12kg) were successfully exsanguinated into cardiac arrest. Mean left ventricular end-diastolic volume, end-diastolic pressure, and stroke work decreased as the hemorrhagic shock class progressed (p < 0.001). The proportion of diastole spent with retrograde coronary flow was also associated with class of hemorrhagic shock (mean 5.6% of diastole in baseline, to 63.9% of diastole in class IV; p < 0.0001), worsening at each class from baseline through class IV. Preload recruitable stroke work (PRSW) decreased significantly in classes II through IV (p < 0.001). Systemic Vascular Resistance (SVR) is associated with class of hemorrhage shock (p < 0.001). Conclusion: With progressive classes of hemorrhagic shock left ventricular function progressively decreased, and the coronary arteries spent a greater proportion of diastole in retrograde flow, with progressively more negative total coronary flow. Preload recruitable stroke work, a load-independent measure of inotropy, also worsened in severe hemorrhagic shock, indicating the mechanism extends beyond the drop in preload and afterload alone.

Relationship between haemodynamic indicators and haemogram in patients with heart failure.

Pulmonary congestion, reduced cardiac output, neurohumoral factor activation, and decreased renal function associated with decreased cardiac function may have various effects on haemograms. The relationship between these factors and haemograms in patients with heart failure has not been sufficiently investigated. Recently, it was suggested that the lungs are an important site for platelet (Plt) biosynthesis and that it is necessary to study the relationship between pulmonary congestion and Plt count in heart failure in detail. In this study, we examined the relationship between various haemodynamic indicators and haemograms in detail using statistical analyses. A total of 345 patients who underwent cardiac catheterization for the evaluation of cardiac function between 1 January 2015 and 31 December 2020 were included in the study. Haemodynamic indices, including left ventricular end-diastolic pressure (LVEDP) and cardiac index (CI), were measured. Plasma noradrenaline (Nor) concentration, estimated glomerular filtration rate (eGFR), white blood cell (WBC) count, haemoglobin (Hb) level, and Plt count were measured using blood samples collected at the same time. Structural equation modelling (SEM) was used to examine the relationship between LVEDP, CI, plasma Nor concentration, eGFR, WBC count, Hb level, and Plt count. Bayesian inference using SEM was performed for Plt count. A total of 345 patients (mean age: 66.0±13.2years) were included in this study, and 251 (73%) patients were men. After simple and multiple regression analyses, path diagrams were drawn and analysed using SEM. LVEDP showed a significant negative relationship with Plt count (standardized estimate: -0.129, P=0.015), and CI showed a significant negative relationship with Hb level (standardized estimate: -0.263, P<0.001). Plasma Nor concentration showed a significant positive relationship with WBC count (standardized estimate: 0.165, P=0.003) and Plt count (standardized estimate: 0.198, P<0.001). The eGFR had a significant positive relationship with Hb level (standardized estimate: 0.274, P<0.001). Bayesian inference using SEM revealed no relationship between LVEDP and Hb level or WBC count but a significant negative relationship between LVEDP and Plt count. LVEDP, CI, plasma Nor concentration, and eGFR were related to WBC count, Hb level, and Plt count in patients with heart failure. There was a strong relationship between elevated LVEDP and decreased Plt count, suggesting that pressure overload on the lungs may interfere with the function of the lung as a site of Plt biosynthesis.

Estimation of Left Ventricular Filling Pressure Using Left Atrial Strain in Coarctation of Aorta.

Left atrial (LA) reservoir strain <18% and booster strain <8% have been proposed as the optimal threshold to detect increased left ventricular (LV) filling pressure in patients with acquired heart disease. The purpose of this study was to determine whether these LA strain cut-off points can detect increased LV filling pressure in adults with coarctation of aorta (COA). This retrospective study included adults with COA (n = 126; age, 36 ± 16 years) who underwent non-simultaneous cardiac catheterization and echocardiography. Increased LV filling pressure was defined as pulmonary artery wedge pressure (PAWP) >12 mm Hg or LV end-diastolic pressure (LVEDP) >16 mm Hg. The median PAWP was 13 mm Hg (interquartile range [IQR], 11-18) and PAWP had a good correlation with LA reservoir strain (r = -0.69; P<.001) and LA booster strain (r = -0.61; P<.001). LA reservoir strain <18% had superior diagnostic power to detect PAWP >12 mm Hg as compared with LA volume index >34 mL/m², septal E/e' >15, lateral E/e' >13, and tricuspid regurgitation velocity >2.8 m/s (P<.05 for all). The median LVEDP was 17 mm Hg (IQR, 14-20) and LVEDP had a modest correlation with LA reservoir strain (r = -0.39; P<.001) and LA booster strain (r = -0.33; P<.01). LA reservoir strain <18% had superior diagnostic power to detect LVEDP >16 mm Hg as compared with LA volume index >34 mL/m², septal E/e' >15, lateral E/e' >13, and tricuspid regurgitation velocity >2.8 m/s (P<.05 for all). These data suggest that LA strain could potentially be used to identify patients with increased LV filling pressure, thereby improving patient selection for cardiac catheterization and interventions.

Echocardiographic Characteristics and Clinical Outcomes of the Hyperdynamic Heart: A ‘Super-Normal’ Heart is not a Normal Heart

A hyperdynamic heart is defined as a left ventricular (LV) with an ejection fraction (EF) above the normal range. Is this favorable? We looked at the diastolic properties of subjects with a hyperdynamic heart and its impact on outcome. Consecutive echocardiography examinations during 5years were evaluated by EF subgroups, including a hyperdynamic heart (EF >70%). All examinations with significant LV hypertrophy or valve disease were excluded. The study included 16,994 subjects. A total of 720 subjects (4.2%) had a hyperdynamic heart. Subjects with a hyperdynamic heart were older, more likely to be women, and more likely to have hypertension, diabetes, and obesity. A total of 20% of patients had a diagnosis of heart failure. This group had a higher heart rate, smaller ventricular size, and the highest relative wall thickness. All indexes of diastolic dysfunction were significantly more prevalent in the hyperdynamic group. This included a higher LV mass, larger left atrial volume, reduced relaxation (smaller mitral e'), longer deceleration time, and higher LV end-diastolic pressures (high mitral E/e' ratio) and peak tricuspid regurgitation gradient. Diastolic dysfunction, defined by an abnormal functional or structural parameter, was present in 78% of the subjects. Survival was significantly lower in the group with a hyperdynamic heart. The Cox regression analysis after adjustment demonstrated reduced survival during a median 9-year follow-up in the hyperdynamic group compared with those with a normal EF (hazard ratio 1.56, 95% confidence interval 1.38 to 1.76, p <0.001). In conclusion, subjects with a hyperdynamic systolic function have increased prevalence of diastolic dysfunction and reduced survival. A hyperdynamic heart is not a normally functioning heart.

Correlation between Echocardiographic Diastolic Parameters and Invasive Measurements of Left Ventricular Filling Pressure in Patients with Takotsubo Cardiomyopathy

The extent of diastolic dysfunction is of clinical importance in the risk stratification and management of patients with Takotsubo cardiomyopathy (TC). Standard echocardiographic indices of diastolic dysfunction have robust predictive ability in assorted disease states, but have not been validated in TC. The aim of this study was to compare Doppler metrics of diastolic function against catheterization-measured filling pressures in TC. Patients with TC who met inclusion and exclusion criteria were evaluated using echocardiography and catheterization performed within 24hours. Both left ventricular (LV) end-diastolic pressure and LV pre-A diastolic pressure were obtained from catheterization tracings. The echocardiographic parameters for diastolic function were extracted using the American Society of Echocardiography recommendations and a previously validated regression equation for mean left atrial pressure (mLAP). A total of 51 patients with TC were included. Patients were predominantly women (72.5%), with a mean age of 58±13years and a mean ejection fraction of 24±10 %. E/e' ratio (septal, average, and lateral) and calculated mLAP correlated positively with catheterization LV pre-A, with fair to moderate correlation (coefficient range, 0.38-0.44). The t-test mean difference between LV pre-A pressure and calculated mLAP was 0.77±7.34mm Hg (95% CI, ±14.68mm Hg) suggesting inconsistent measures. mLAP also exhibited poor diagnostic ability to discriminate elevated LV pre-A diastolic pressure, with an area under the receiver operating characteristic curve of 0.69 (95% CI, 0.50-0.88). Commonly used echocardiographic parameters for diastolic function demonstrated less-than-optimal correlation, with poor sensitivity and specificity, compared with invasively measured LV end-diastolic pressure or LV pre-A wave diastolic pressure in patients with TC. Precise characterization of LV filling pressure in patients with TC using contemporary noninvasive echocardiographic parameters appears challenging. Invasive measurements of filling pressure should remain the gold standard for optimal risk stratification and management of patients with TC.

CLINICAL AND DEMOGRAPHIC FEATURES ASSOCIATED WITH ELEVATED LEFT VENTRICULAR END-DIASTOLIC PRESSURE IN PATIENTS UNDERGOING PRIMARY PERCUTANEOUS CORONARY INTERVENTION

Objectives: Prognostic importance of left ventricular end-diastolic pressure (LVEDP) is well established, hence, it is important to understand the factors associated with increased LVEDP for individualized risk stratification of ST-segment elevation myocardial infarction (STEMI) patients. There is dearth of data regarding clinical associates of elevated LVEDP, therefore, the purpose of current study was to evaluate the clinical indicators and phenotype of elevated LVEDP in STEMI patients undergoing primary percutaneous coronary intervention (PCI).&#x0D; Methodology: This descriptive observational study included patients diagnosed with STEMI and undergone primary PCI. LVEDP was measured using a fluid-filled pig-tail catheter before reperfusion but after angiography. Elevated LVEDP was taking as &gt;25 mmHg.&#x0D; Results: A total of 498 patients were included, 23.7% (118) were female patients and mean age was 53.7 ± 11.7 years. Distribution of LVEDP was ≤15 mmHg in 48% (239), 15-25 mmHg in 42% (209), and &gt;25 mmHg in remaining 10% (50) of the patients. Elevated LVEDP was found to be associated with increased heart rate (HR) with adjusted odds ratio of 1.05 [1.02-1.08], decreased systolic blood pressure (SBP) (0.95 [0.9-0.99]), Killip class II or high (9.36 [3.38-25.9]), and hypertension (4.63 [1.55-13.82]).&#x0D; Conclusion: Hemodynamic instability at presentation such as elevated HR, reduced SBP, higher Killip class and hypertension are the key indicators of elevated LVEDP.

Noninvasive Evaluation of Cardiac Chamber Pressures Using Subharmonic-Aided Pressure Estimation With Definity Microbubbles

BackgroundNoninvasive and accurate assessment of intracardiac pressures has remained an elusive goal of noninvasive cardiac imaging. ObjectivesThe purpose of this study was to investigate if errors in intracardiac pressures obtained noninvasively using contrast microbubbles and the subharmonic-aided pressure estimation (SHAPE) technique are <5 mm Hg. MethodsIn a nonrandomized institutional review board–approved clinical trial (NCT03243942), patients scheduled for a left-sided and/or right-sided heart catheterization procedure and providing written informed consent were included. A standard-of-care catheterization procedure was performed advancing clinically used pressure catheters into the left and/or right ventricles and/or the aorta. After pressure catheter placement, patients received an infusion of Definity microbubbles (n = 56; 2 vials diluted in 50 mL of saline; infusion rate: 4-10 mL/min) (Lantheus Medical Imaging). Then SHAPE data was acquired using a validated interface developed on a SonixTablet scanner (BK Medical Systems) synchronously with the pressure catheter data. A conversion factor (mm Hg/dB) was derived from SHAPE data and measurements with a SphygmoCor XCEL PWA device (ATCOR Medical) and was combined with SHAPE data from the left and/or the right ventricles to obtain clinically relevant systolic and diastolic ventricular pressures. ResultsThe mean value of absolute errors for left ventricular minimum and end diastolic pressures were 2.9 ± 2.0 and 1.7 ± 1.2 mm Hg (n = 26), respectively, and for right ventricular systolic pressures was 2.2 ± 1.5 mm Hg (n = 11). Two adverse events occurred during Definity infusion; both were resolved. ConclusionsThese results indicate that the SHAPE technique with Definity microbubbles is encouragingly efficacious for obtaining intracardiac pressures noninvasively and accurately. (Noninvasive, Subharmonic Intra-Cardiac Pressure Measurement; NCT03243942)

Reducing brain TACE activity improves neuroinflammation and cardiac function in heart failure rats.

Tumor necrosis factor (TNF)-α converting enzyme (TACE) is a key metalloprotease mediating ectodomain shedding of a variety of inflammatory mediators, substrates, and growth factors. We previously reported that TACE-mediated production of TNF-α in the hypothalamic paraventricular nucleus (PVN) contributes to sympathetic excitation in heart failure (HF). Here, we sought to determine whether central interventions in TACE activity attenuate neuroinflammation and improve cardiac function in heart failure. Myocardial infarction-induced HF or sham-operated (SHAM) rats were treated with bilateral paraventricular nucleus microinjection of a TACE siRNA or a 4-week intracerebroventricular (ICV) infusion of the TACE inhibitor TAPI-0. Compared with SHAM rats, scrambled siRNA-treated HF rats had higher TACE levels in the PVN along with increased mRNA levels of TNF-α, TNF-α receptor 1 and cyclooxygenase-2. The protein levels of TNF-α in cerebrospinal fluid and phosphorylated (p-) NF-κB p65 and extracellular signal-regulated protein kinase (ERK)1/2 in the PVN were also elevated in HF rats treated with scrambled siRNA. The expression of these inflammatory mediators and signaling molecules in the PVN of HF rats were significantly attenuated by TACE siRNA. Interestingly, the mRNA level of TNF-α receptor 2 in the PVN was increased in HF treated with TACE siRNA. Moreover, sympathetic excitation, left ventricular end-diastolic pressure, pulmonary congestion, and cardiac hypertrophy and fibrosis were reduced by PVN microinjection of TACE siRNA. A 4-week treatment with intracerebroventricular TAPI-0 had similar effects to ameliorate these variables in HF rats. These data indicate that interventions suppressing TACE activity in the brain mitigate neuroinflammation, sympathetic activation and cardiac dysfunction in HF rats.