Left Ventricular Pressure Research Articles

Prognostic value of left atrial strain index (LASI) in patients with heart failure with preserved ejection fraction

Abstract Background Left atrial (LA) strain has been proposed as an additional echocardiographic parameter to conventional diastolic dysfunction assessment for the estimation of elevated left ventricular end-diastolic pressure (LVEDP). Recently, left atrial strain index (LASI) has been introduced, which integrates by a machine-learned algorithm the entire strain curve (not limited to either the reservoir or contractile function) into a single parameter, and which was able to distinguish elevated versus normal LVEDP upon validation with invasive measurements. However, the prognostic value of LASI has not been widely established in the clinical setting. Purpose To investigate the prognostic value of LASI in patients with heart failure with preserved ejection fraction (HFpEF). Methods A total of 211 diagnosed HFpEF patients from a dedicated outpatient program were retrospectively analysed. Patients with cardiac devices or low image quality for LA analyses were excluded. Extensive echocardiographic analysis was performed, and LASI was assessed: positive values indicating elevated LVEDP and negative values identifying normal LVEDP (Figure 1). Study outcome was a composite of heart failure hospitalisation and all-cause mortality. Results From the total population, 117 (55%) patients had elevated LVEDP based on LASI and 94 (45%) normal LVEDP. Patients with elevated LVEDP were slightly older (77±6 vs. 74±8 years, p=0.003), had more often atrial fibrillation (61% vs. 10%, p<0.001), higher HFA-PEFF score (HFA-PEFF≥5 69% vs. 53%, p=0.017) and NT-proBNP (135 [62-194] vs. 44 [25-81] pmol/L, p<0.001), and more impaired diastology parameters [LA indexed volume 57±20 vs. 44±12 ml/m2, p<0.001; average E/e’ 13±5 vs. 11±3, p=0.005; tricuspid jet velocity 2.8±0.4 vs 2.6±0.4 cm/s, p=0.036). During a median follow-up of 61 months, a total of 95 events were recorded. The elevated LVEDP group had worse outcome compared to the normal LVEDP group classified based on LASI (p<0.001, Figure 1). When stratifying first according to HFA-PEFF score (cut-off ≥5) and then into LVEDP groups, patients with the elevated LVEDP still had worse outcomes, regardless of HFA-PEFF score (Figure 2). Uni- and multivariable survival analysis demonstrated that the LASI classification was independently associated with outcome, after correcting for age, sex, NYHA class, comorbidities, kidney function and HFA-PEFF score (HR 2.716 [1.610-4.583], p<0.001). Likelihood analysis showed an incremental value upon addition of LASI to the clinical factors (ꭓ2 44 to 56, p<0.001). Subgroup analysis on patients in sinus rhythm also demonstrated similar association of LASI to outcomes, adding significant value to other parameters. Conclusion LASI is significantly associated with outcome in HFpEF patients, and can be an adjunct to current methods of diastolic dysfunction assessment to improve risk stratification of these patients.

Left ventricular systolic function after liver transplantation

Abstract Background Liver transplantation (LT) is the only curative therapy for patients with end stage liver disease. However, LT may challenge the cardiovascular system , unmasking left ventricular (LV) systolic dysfunction. In the present study we evaluated LV systolic function of patients with end stage liver disease, after the transplantation, based on tissue Doppler imaging (TDI) and strain analysis. Methods and Results We recruited 32 patients (age 54.59± 11.8 years, 23 % male) with preserved LV ejection fraction (EF) who underwent LT. Left ventricular systolic function was evaluated in terms of conventional parameters and deformation analysis. Left ventricular dimensions (p=0.81), LV EF (p=0.46) and systolic pulmonary artery pressure (p=0.16) did not change after the LT . Regarding TDI analysis, we observed marked decrease in septal and lateral peak systolic velocities . (LV septal Sa 0.08±0.009 to 0.07±0.008 m/s, p=0.0001, and LV lateral Sa 0.09±0.02 to 0.08±0.01, p=0.0001). Based on 2D strain analysis, there was significant impairment in LV global longitudinal strain (GLS) measurements, after LT, when compared to the parameters before the operation (- 20.24 % ± 3.52 to -16.05 % ± 2.55, p=0.0001). Conclusion Systolic heart failure is an important clinical condition post LT in the first year which has a devastating effect on the quality of lives of the patients. Detailed assessment of LV systolic function with preserved EF, helps to identify high risk patients for manifest heart failure.

The influence of left-heart myopathy on the diagnosis and treatment of mitral valve stenosis: an in silico trial

Abstract Background The shift in mitral stenosis (MS) aetiology from rheumatic to calcific valve disease, commonly seen in elderly patients with cardiomyopathy, challenges the differentiation between valve- or tissue-related causes of haemodynamic abnormalities. Purpose This study examines the impact of left-heart myopathy on the echocardiographic assessment of MS severity and acute haemodynamic effects following mitral valve (MV) intervention. Methods The CircAdapt model of the human cardiovascular system was used to evaluate the effect of MS on cardiac haemodynamics in a virtual patient cohort with broad ranges of impaired left atrial (LA) function and reduced left ventricular (LV) compliance. Mean gradient (MG) and pressure half-time (PHT) were derived for MS severity assessment, alongside LV and LA pressure traces to quantify the haemodynamic consequence of MV intervention. Results Depending on myocardial abnormalities, the MG varied by only 10%, 5% and 5% for mild, moderate and severe MS, respectively. Reduced LV compliance resulted in disproportionately lower PHT causing overestimation of the PHT-derived MV area up to 1.43 cm2. Following virtual MV intervention for moderate to severe MS, mean left atrial pressure (mLAP) decreased by 50% in presence of healthy myocardium but only 4% for combined LV and LA dysfunction. In patients with reduced LV compliance, LV end-diastolic pressure remained elevated despite MV intervention. Conclusions The virtual patient cohorts indicate that the MG is a robust metric for MS severity regardless of left-heart myopathy, whereas PHT may reveal underlying impaired LV compliance. However, neither MG nor PHT predict changes in mLAP following intervention. Recognizing the significance of distinguishing between increased left-heart pressures driven by valvular or tissue factors is therefore crucial for clinical decision-making. graphical abstract methods

Trajectories and determinants of myocardial work indices in patients with acute myocardial infarction after primary percutaneous coronary intervention

Abstract Backgrounds The myocardial work indices (MW indices) are novel echocardiographic parameters that quantify myocardial deformation and concomitant left ventricular pressure. However, there is little current data on trajectories and determinants of MW indices after acute myocardial infarction (AMI). Purpose We aimed to evaluate the trajectories of myocardial work indices and their relationship with left ventricle (LV) functional recovery and remodelling in patients with AMI after primary percutaneous coronary intervention (PCI). Methods Thirty-one prospectively recruited patients (28 men; mean age, 64 ± 9 years) underwent transthoracic echocardiography 7.7±3.8 days after PCI for the first ST-elevation AMI. LV function was evaluated at baseline and the 6-month follow-up. MW index (MWI), constructive MW (CMW), myocardial wasted work (MWW), MW efficiency, and (MWE) were measured globally and segmentally. The myocardial area at risk (AAR) and the remote area were based on the culprit coronary arterial segment, determined from the invasive coronary angiography. Levels of troponin T and NT-proBNP were assessed. Results The mean LV end-diastolic volume (EDV), LV end-systolic volume (ESV), LV ejection fraction (EF), and global longitudinal strain were similar at baseline and the 6-month follow-up (94.7±27.7 vs 93.6±30.1 ml, p=0.7, 42.7±17.1 vs. 40.8±19.1 ml, p=0.4, 55.8±6.9 vs. 57.5±7.3%, p=0.2, and -14.9±4.6 vs. -15.4±3.9%, p=0.3, respectively). The global MWI, MCW, MWW and were significantly improved at the 6-month follow-up (p<0.001, p<0.001, p=0.002, and p=0.03, respectively). Furthermore, in AAR, regional MWI, MCW, and MWW values significantly improved at the 6-month follow-up (all p<0.001), whereas no changes in MWE were observed . MWI and MCW significantly improved in the remote areas (p<0.001, and p=0.02, respectively) , but other indicators remained unchanged (Table 1). The global MWI and MCW values at baseline were inversely correlated with peak levels of troponin T (r= - 0.60, p<0.001, and r= -0.52, p= 0.002, respectively) and NT-proBNP (r= -0.49, p= 0.007, and r= -0.47, p=0.01, respectively). Furthermore, the global MWI and MCW showed a significant positive correlation with EF at baseline (r= 0.66, p<0.001, and r= 0.56, p<0.001, respectively) and 6-month follow-up (r= 0.68, p<0.001, and r= 0.69, p<0.001, respectively), but a negative correlation with ESV (Figure 1). However, there was no significant correlation between MW indices and EDV. Conclusion Patients with AMI who underwent primary PCI showed improved global and regional LV performance 6 months post-infarction, as demonstrated by MW indices. Decreased global MWI and MCW are associated with higher baseline levels of NT-proBNP, higher baseline levels of troponin T, reduced EF, and increased end-systolic volume. These results provide evidence that MW indices are potential markers of the severity of myocardial injury and remodelling after AMI.

Enhancing myocardial function assessment in hypertension patients through the integration of exercise stress echocardiography and pressure-strain loop technique.

Abstract Objective This study aims to investigate the characteristics of myocardial work(MW) and reserve function in left ventricular remodeling hypertension (LVRH) patients through exercise stress echocardiography (ESE) and pressure-strain loop (PSL) technique,and further to investigate the associations of MW parameters with the exercise capacity in this observational study. Methods One hundred and five hypertensive patients with left ventricular remodeling{Left ventricular mass index (LVMI) ≥115 g/m2 (male) and LVMI ≥95 g/m2 (female)} underwent ESE examination according to established guidelines, the test was terminated at 85% of the target heart rate. Additionally, 59 healthy subjects were included as a control group. Speckle tracking software was utilized for analysis, the myocardial work parameters were calculated by combining the longitudinal strain with the noninvasive left ventricular pressure curve.Exercise capacity and reserve function,global and segment work index were evaluated and analysed. Results Global work index (GWI) , global constructive work (GCW) and global wasted work (GWW) were significantly increased both at rest and peak in LVRH group, while global work efficincy(GWE) were decreased. The GWI from basal to apiex both at rest and peak showed increasing trend in the order of the control group. GWI-rest showed prominent relation with exercise metabolic equivalent(METs)(r=-0.502,p＜0.001),E/e-peak ( (r=0.612,p＜0.001), ΔGobal longitudinal strain (GLS) (r=0.421,p＜0.001).Further GWI-rest and ΔGWI as well as E/e-peak add increased predictive utility of exercise capacity, superior to the change in GLS .The myocardial work reserve function can be available for predicting patients with LVRH{ΔGWI，AUC: 0.869 (95%CI,0.815−0.924), providing incremental value for LVRH diagnostic performance. Conclusion MW parameters can reflect the contractile force under hemodynamic overload,provide a more comprehensive and compelling perspective for evaluating cardiac function. GWI is an important predictor of systolic and diastolic function and a variable closely related to exercise endurance in patients with LVRH. comparison rest and peak parameters ROC for identify LVH patients

A novel imaging-based method to estimate left ventricular filling pressure

Abstract Background There is a clinical need in heart failure diagnostics to have a non-invasive measure of left ventricular (LV) filling pressure. Echocardiographic parameters may be used to differentiate between normal and elevated left ventricular (LV) filling pressure, but do not provide a quantitative estimate of the filling pressure. Purpose To establish a non-invasive method for estimating LV filling pressure and construction of the LV diastolic pressure curve. Methods Retrospective study in 100 patients with suspected coronary artery disease. Ground truth filling pressure (i.e. LV pre-atrial contraction pressure, which is shown to approximate mean left atrial pressure) was measured by LV micromanometer-tipped catheters. Non-invasive filling pressure was estimated as the sum of minimum LV pressure (minPLV) and the maximum early-diastolic atrio-ventricular pressure difference (∆PA-V), as shown in Figure 1. MinPLV was estimated by a regression model trained in 81 patients, which included an estimate of the time constant of τ (Figure 1) and echocardiographic and demographic parameters. ∆PA-V was computed by a simplified Navier-Stokes momentum conservation equation. Accuracy of filling pressure estimate was evaluated in a test cohort of 19 patients. Results The strongest predictor of minPLV was τ (R=0.71) followed by LA reservoir strain (R=0.65), LV systolic pressure (R=0.23) and body mass index (R=0.37), all of them independent predictors. There was good agreement between estimated and measured τ (Bias -0.0069s and limits of agreement <0.0195s). When combining estimated τ and the three other predictors in a regression model, there was good agreement between estimated and measured minPLV: Bias -0.5 mmHg, limits of agreement <1.9 mmHg (±2SD). Estimated LV filling pressure also showed good agreement with measured values: Bias 0.0 mmHg, limits of agreement <3.1 mmHg, shown in Figure 2. The diastolic pressure curve was estimated with good accuracy (diastolic meanPLV had bias and limits of agreement were respectively 0.2 and <3.2mmHg). Conclusions The proposed non-invasive method estimated LV filling pressure with good accuracy in a population with coronary artery disease. The method also allowed approximation of the LV diastolic pressure curve. The method needs validation in larger populations and in other phenotypes. Method to calculate LV filling pressure LV filling pressure (pre-A) agreement

Natural shear wave imaging outperforms conventional echocardiographic parameters in detecting elevated left ventricular filling pressures

Abstract Background Current conventional echocardiographic assessment of diastolic function relies on predicting left ventricular (LV) filling pressure as a surrogate of diastolic function. However, the current guidelines algorithm for estimation of LV filling pressures is complex. High frame rate (HFR) Shear wave (SW) imaging is emerging as a novel parameter for assessing myocardial stiffness, a key determinant of diastolic function. Natural SW can be induced, e.g., by mitral valve closure (MVC) and their propagation speed is directly related to myocardial stiffness. Little is known, however, to what extent SW after MVC can reflect diastolic LV filling pressures. Purpose We aimed at investigating the relationship between natural SW and LV diastolic filling pressures in comparison to conventional echocardiographic parameters. Methods Thirty patients (mean age 68.4±9.9 years) scheduled for clinically indicated left heart catheterization were prospectively recruited irrespective of diastolic function status. Conventional as well as HFR echocardiography (ca. 1200 frames/second) was performed immediately after the catheterization. We tracked SW occurring after MVC along the ventricular septum in the parasternal long axis view using an anatomical M-mode from base to apex colour coded for tissue acceleration. SW appeared immediately after as tilted green bands and their propagation velocity was measured semi-automatically (Figure 1). Results In our cohort, the LV mid-diastolic pressure (LVMDP) ranged from 5 to 19 mmHg, while the LV end-diastolic pressure (LVEDP) ranged from 7.5 to 29.5 mmHg. LV filling pressures were considered elevated if exceed 15 mmHg for LVMDP and 16 mmHg for LVEDP. Out of the conventional echocardiographic parameters, only mitral inflow to mitral relaxation velocity ratio (E/e’) correlated moderately with LV filling pressures (r=0.47, p=0.009 for LVMDP; and r=0.49, p=0.006 for LVEDP) (Figure 2 A,B). The accuracy of the conventional E/e’ cut-off value of 14 to predict elevated LV filling pressure is 76% for LVMDP and 70% for LVEDP (Figure 2C). SW velocities after MVC correlated strongly with diastolic LV pressures (r=0.65, p<0.001 for LVMDP; r=0.78, p<0.001 for LVEDP) (Figure 2 D,E). Interestingly, a cut-off value for SW velocity of 5.8 m/s showed an excellent ability to discriminate raised LVMDP (AUC: 0.93; sensitivity: 80%, specificity: 80%, accuracy: 80%) and elevated LVEDP (AUC: 0.96 ; Sensitivity: 89%, specificity: 95%, accuracy: 93%) (Figure 2F). Conclusions Our preliminary data showed that SW velocities at end-diastole are strongly related to LV filling pressures and can predict elevated LV filling pressures more accurately than conventional echocardiographic parameters. This ongoing study shows the potential of natural shear wave imaging as a promising innovative tool for assessment of diastolic function. Figure 1 Figure 2

Evaluation of LVEDP Change During High-Risk PCI With and Without Impella Support (ELVIS)—A Pilot Trial

Background: The decision-making process to use percutaneous mechanical circulatory support in the context of elective high-risk percutaneous coronary intervention (HRPCI) is complex and evolving. The aim of this study is to evaluate the left ventricular end-diastolic pressure (LVEDP) as a parameter to identify patients that may benefit from a protected HRCPI (pHRPCI) procedure. Methods: Overall, 62 patients (pHRPCI n = 31 vs. non-pHRPCI n = 31) with a complex coronary artery disease and a left ventricular ejection fraction (LVEF) ≤35% were included. The primary endpoint was defined as a change in LVEDP and its correlation with laboratory measurements. The secondary safety endpoint was a composite of the incidence of major in-hospital adverse cardiac and cerebrovascular events (MACCE). Results: Baseline characteristics were similar, including age (pHRPCI 72.8 ± 8.8 vs. non-pHRPCI 75.0 ± 10.4; p = 0.408), male (pHRPCI 83.9% vs. non-pHRPCI 96.8; p = 0.195), pre-PCI Syntax Score (pHRPCI 33.9 ± 13.1 vs. non-pHRPCI 35.4 ± 12; p = 0.643), post-PCI Syntax Score (pHRPCI 7.4 ± 6.2 vs. non-pHRPCI 9.6 ± 8.4; p = 0.239) and baseline LVEDP between the groups (pHRPCI 18.5 ± 10.5 mmHg vs. non-pHRPCI 15.7 ± 8.1 mmHg; p = 0.237). There was a trend to a lower LVEF in the pHRPCI group (26.4 ± 6.7% vs. 29.4 ± 5%; p = 0.051). The primary endpoint analysis revealed a significant change in LVEDP (pHRPCI −4.7 ± 9 mmHg vs. non-pHRPCI +3.1 ± 7.5 mmHg; p < 0.001) that did not correlate with changes in creatinine (p = 0.285), NT-proBNP (p = 0.383) or troponin (p = 0.639) concentrations within 24 h. Overall, low rates of in-hospital (pHRPCI 6.5% vs. non-pHRPCI 3.2%; p = 0.999) and 90-days (pHRPCI 12.9% vs. non-pHRPCI 12.9%; p = 0.999) MACCE were observed in both groups. Conclusions: Protected HRPCI leads to a significant reduction in LVEDP without influencing biomarkers of myocardial damage. There was no difference in MACCE rates between the groups.

Astragaloside IV Alleviates Myocardial Fibrosis After Myocardial Infarction Through SIRT3/β-catenin/PPARγ Signaling Pathway

Background Myocardial fibrosis following myocardial infarction (MI) is linked to decreased cardiac function and heart failure. Astragaloside IV (AST IV), a component of traditional Chinese medicine, has shown promise in animal studies for improving cardiac function. Purpose This study intends to investigate the role of AST IV in MI and its correlation with the sirtuin-3 (SIRT3)/β-catenin/peroxisome proliferator-activated receptor gamma (PPARγ) signaling pathway. Methods After the establishment of an animal model of MI, 60 rats were divided into a control group, model group (MI group), positive control group (sham group), low-dose AST IV group (0.8 mg/100 g), and high-dose AST IV group (3 mg/100 g). The animals were injected once a day for 4 consecutive weeks. To further investigate the mechanism of action of AST IV, another nine rats from the model group were randomly divided into the 3TYP group (5 mg/100 g), SKL2001 group (20 µmol/L, 10 mL/kg), and T0070907 group (0.15 mg/100 g), with three rats in each group. The rats in each group were intervened once a day by intraperitoneal injection and once a day by gavage for 4 consecutive weeks. Hemodynamics, cardiac function, ventricular weight, and infarct area were assessed at 1, 2, and 4 weeks post-surgery. Myocardial collagen content in the non-infarcted area was measured, the expression rate of transforming growth factor-beta and ED-positive cells was calculated, and reverse transcription polymerase chain reaction was used to detect SIRT3, β-catenin, and PPARγ mRNA expression. Results The left ventricular ejection fraction, short-axis shortening rate, and left ventricular mass in the model group were decreased obviously. AST IV treatment decreased systolic blood pressure, +dp/dtmax, –dp/dtmax, and left ventricular end-diastolic pressure, as well as reduced myocardial collagen deposition in rat hearts ( p < 0.05). AST IV inhibited the SIRT3/β-catenin/PPARγ signaling pathway when alleviating myocardial fibrosis. Intervention with SIRT3 blocker 3-TYP, β-catenin agonist SKL2001, and PPARγ blocker T0070907 reversed the inhibitory effect of AST IV on the signaling pathway. Conclusion AST IV exhibits significant anti-fibrotic effects, effectively reducing collagen deposition in the MI model, improving cardiac function parameters, and decreasing markers such as creatine kinase-MB. It significantly regulates SIRT3, β-catenin, and PPARγ to exert cardioprotective effects. The key mechanism involves inhibiting the SIRT3/β-catenin/PPARγ, offering an innovative strategy for post-MI treatment.

Validity and Accuracy of the Derived Left Ventricular End-Diastolic Pressure in Impella 5.5.

Consensus regarding on-support evaluation and weaning concepts from Impella 5.5 support is scarce. The derived left ventricular end-diastolic pressure (dLVEDP), estimated by device algorithms, is a rarely reported tool for monitoring the weaning process. Its validation and clinical accuracy have not been studied in patients. We assess dLVEDP's accuracy in predicting pulmonary capillary wedge pressure (PCWP) and propose a corrective equation. We included 29 consecutive patients treated with Impella 5.5: 12 in a generation cohort and 17 in a validation cohort. dLVEDP and PCWP were measured 5-fold every 8 hours during support, totaling 698 series with 3490 measurements. Variables such as Impella 5.5 performance level, heart rhythm, pacemaker settings, sex, mechanical ventilation, and body mass index were recorded. Linear regression was used to correct dLVEDP-PCWP discrepancies. Analysis included Bland-Altman plots, linear regression, histograms, and violin plots. The raw dLVEDP and PCWP data did not coincide satisfactorily. The Impella 5.5 dLVEDP overestimation was 3.5±1.5 mm Hg (mean±SD), increasing with higher pressures and unaffected by cardiac rhythm, mechanical ventilation, and performance levels. Statistical correction using the formula modified dLVEDP=-0.457+(1-sex[1=male, 0=female])×0.719-0.0496× body mass index+1.015×body surface area+0.811×dLVEDP significantly reduced the overestimation (P<0.01) to 0.0±1.2 mm Hg. dLVEDP, calculated by the Impella 5.5 Smart Algorithm, is a feasible and effective tool for continuously monitoring PCWP at performance levels 3 to 9. Correction of dLVEDP by using the described equation further enhances its accuracy. Hence, hemodynamic surveillance via dLVEDP may aid in managing and weaning temporary microaxial support, potentially reducing the need for continuous monitoring with a Swan-Ganz catheter.

Inhibition of p70 Ribosomal S6K1 Protects the Myocardium against Ischemia/Reperfusion-Induced Necrosis through Downregulation of RIP3.

Myocardial ischemia-reperfusion (I/R) injury refers to cell damage that occurs as a consequence of the restoration of blood circulation following reperfusion therapy for cardiovascular diseases, and it is a primary cause of myocardial infarction. The search for nove therapeutic targets in the context of I/R injury is currently a highly active area of research. p70 ribosomal S6 kinase (S6K1) plays an important role in I/R induced necrosis, although the specific mechanisms remain unclear. This study aims to explore the effects of inhibiting S6K1 on myocardial I/R injury and its potential mechanisms. A rat myocardial I/R model was created and treated with the S6K1-specific inhibitor PF-4708671. Hematoxylin-eosin (H&E) staining was applied to evaluate the pathological changes in cardiac tissues. 2,3,5-triphenyltetrazolium chloride (TTC) staining was used to measure the area of myocardial infarction (MI). Left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP), the maximum rate of increase in left ventricular pressure (+dp/dtmax), and the maximum rate of the decrease in left ventricular pressure (-dp/dtmax) were measured using ultrasonic echocardiography. The expression levels of cardiac troponin-1 (cTn-1), lactate dehydrogenase (LDH), creatine kinase MB (CK-MB), and aspartate aminotransferase (AST) were determined by enzyme-linked immunosorbent assay (ELISA). Terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining and propidium iodide (PI) staining were used to examine the apoptosis and necrosis of myocardial tissues. The expressions of apoptotic-related proteins, and key molecules of necrosis were detected by western blot. The relationship between S6K1 and receptor-interacting protein kinase 3 (RIP3) was analyzed by immunoprecipitation. Inhibition of S6K1 reduces I/R-induced myocardial tissue damage, improves myocardial function, and inhibits myocardial tissue necrosis (p < 0.05). In addition, RIP3 is a direct target of S6K1, and activation of RIP3 blocked the protective effect of the S6K1 inhibitor PF-4708671 against myocardial I/R injury (p < 0.05). Inhibition of S6K1 protects against myocardial I/R injury by down-regulating RIP3, suggesting that targeting S6K1 may offer a novel approach for intervention in myocardial I/R injury.

Imaging-based method to quantify left ventricular diastolic pressures.

To establish an imaging-based method to quantify left ventricular (LV) diastolic pressures. In 115 patients suspected of coronary artery disease, LV pressure was measured by micromanometers and images by echocardiography. LV filling pressure was measured as LV pre-atrial contraction pressure (pre-A PLV). Based on previous observations we hypothesized that pre-A PLV approximates the sum of minimum PLV and maximum transmitral pressure difference. Parameters used for pressure estimates included LV volumes and strain, left atrial strain, mitral flow velocities, systolic arterial cuff pressure and body mass index. Minimum PLV was estimated by predictors identified in a derivative cohort (n=81). Mitral pressure difference was calculated by a simplified Navier-Stokes equation. Accuracy of estimates of minimum PLV, pre-A PLV and end-diastolic PLV were investigated in a testing cohort (n=19). Patient-specific LV diastolic pressure curves were constructed by adjusting a reference curve according to pressure estimates at key diastolic events.There was good agreement between estimated and measured pre-A PLV: Bias 0.0, limits of agreement <3.1 mmHg (±1.96SD). Estimated minimum PLV and end-diastolic PLV also showed good agreement with measured pressures. Furthermore, there was good agreement between measured and estimated LV diastolic pressure curves, quantified as mean LV diastolic pressure: Bias 0.2, limits of agreement <3.2 mmHg. The proposed non-invasive method provided estimates of minimum PLV, pre-A PLV and end-diastolic PLV, each reflecting different features of diastolic function. Additionally, it provided an estimate of the LV diastolic pressure curve. Validation in larger populations with different phenotypes is necessary to determine the validity of the method in clinical practice.

Cardiac features in patients with hemodynamically acquired left ventricular end diastolic pressure

Cardiac features in patients with hemodynamically acquired left ventricular end diastolic pressure

Pimobendan oral solution is bioequivalent to pimobendan chewable tablets in beagle dogs.

Myxomatous mitral valve disease (MMVD) is frequently diagnosed in small breed dogs. Pimobendan oral solution has been developed to improve dosing accuracy in small and toy breed dogs. Demonstrate bioequivalence of pimobendan oral solution with pimobendan chewable tablets using a pharmacokinetic and a pharmacodynamic study in healthy purpose bred dogs. In the pharmacokinetic study, 24 beagle dogs were dosed in a 4-period crossover design. In the pharmacodynamic study, 4 mongrel and 2 beagle dogs implanted with telemetry probes were included in a 2-way crossover design. Both studies were designed as prospective, randomized crossover trials. Dogs were given single doses of 5 mg/dog of either formulation followed by serial blood sampling for determination of pimobendan and O-desmethyl-pimobendan (ODMP; main metabolite). Because of high variability in the pharmacokinetics, the reference scaled average bioequivalence (RSABE) method was applied. For the pharmacodynamic study, animals were dosed with 0.25 mg/kg of either formulation. Baseline corrected left ventricular maximal pressure (LVdP/dtmax) and heart rate were recorded continuously and compared with a predefined bioequivalence threshold. Pimobendan was verified as a high variability drug. Based on the RSABE method, both formulations were bioequivalent. Pharmacodynamic results supported bioequivalence. The novel oral solution of pimobendan was found to be bioequivalent, both applying the Food and Drug Administration (FDA) supported RSABE method and based on pharmacodynamic data. Thus, the novel liquid formulation can be used to facilitate accurate dosing of small and toy breed dogs.

Increased left ventricular end-diastolic pressure is associated with impaired subendocardial myocardial perfusion in aortic stenosis

Increased left ventricular end-diastolic pressure is associated with impaired subendocardial myocardial perfusion in aortic stenosis

The effectiveness of prolonged hypothermic preservation of isolated rat hearts using oxygen, medical nitrous oxide and carbon monoxide gas mixtures.

The possibility of using an oxygen-nitrous oxide mixture for prolonged hypothermic preservation of rat heart for 24h was investigated. A comparative analysis of restoration of functional activity of hearts in the groups of 24-h preservation at +4°C with different gases (O2, N2) and gas mixtures (CO+O2, N2O+O2, N2+O2, N2O+N2) was carried out. It was shown that the presence of oxygen in the gas mixture was the key factor for heart preservation. No stable heart preservation was observed in oxygen-free mixtures. At the same time, preservation in pure oxygen showed a significantly lower level of cardiac recovery compared to preservation in gas mixtures O2+CO (6.5 atm.) and O2+N2O (6.5 atm.). LVDP (left ventricular developed pressure) values were 30±19mmHg and 46±9mmHg, respectively, with no significant differences found. The decrease in LDVP after 24h of storage was 26-40% of the intact control. The results obtained indicate the presence of pronounced synergistic effects of both gases during 24-h heart preservation, which is confirmed by data of marker genes Nfe2l2, Nox1, Prdx1, Hif1a, Nos2, Slc2a4, Ucp-1, Jun, Casp3 expression analysis and myocardial infarction damage level data. The more frequent occurrence of arrhythmias was observed in the oxygen-nitrous oxide group compared with the CO group, and the mechanism of this phenomenon is unclear. Nevertheless, the already medically approved N2O+O2 gas mixture could serve as a balanced choice for future improvements, offering a shorter duration of cardiac preservation compared to the CO+O2 mixture, while ensuring safety in its use.

Central venous pressure as a method of optimising atrio-ventricular delay after cardiac surgery.

Haemodynamic atrioventricular delay (AVD) optimisation has primarily focussed on signals that are not easy to acquire from a pacing system itself, such as invasive left ventricular catheterisation or arterial blood pressure (ABP). In this study, standard clinical central venous pressure (CVP) signals are tested as a potential alternative. Sixteen patients with a temporary pacemaker after cardiac surgery were studied. AV delay optimisation was performed by alternating between a reference AVD of 120ms and tested settings ranging from 40 to 280ms, with 8 replicates for each setting. Alongside (a) the raw data, three methods of correcting for respiration were tested: (b) limiting analysis to a respiratory cycle, (c) asymmetric least squares (ALS) and (d) discrete wavelet transform (DWT). The utility of a quality control step was tested. CVP signals were a mirror image of the systolic ABP signals: The four R values were -0.674, -0.692, -0.631, -0.671 respectively (all p<0.001). With quality control, the mirror image was best for DWT (R = -0.76, p<0.001), with the CVP and ABP optima agreeing well (R = 0.78, p<0.001). The automated quality control signal correctly predicted the gap between the AVD optima calculated from ABP and CVP (R = 0.8, p<0.001). Central venous pressure signals could be used to optimise AVD, because they have a reliable inverse relationship with ABP when pacemaker settings undergo protocolised testing. However, protocols need careful design to circumvent spontaneous biological variability.

The impact of left ventricular end diastolic pressure on adverse clinical outcome between subjects with preserved and reduced left ventricular ejection fraction

The impact of left ventricular end diastolic pressure on adverse clinical outcome between subjects with preserved and reduced left ventricular ejection fraction

Optimal ablation pattern on intraprocedural echocardiography is associated with favorable clinical outcomes of alcohol septal ablation for hypertrophic obstructive cardiomyopathy.

Alcohol septal ablation (ASA) is used to treat drug-refractory hypertrophic obstructive cardiomyopathy (HOCM). Intraprocedural echocardiography is essential for identifying the septal area perfused by each septal branch; however, its role in determining the procedural endpoint of ASA remains unclear. This retrospective study aimed to evaluate the impact of intraprocedural echocardiographic findings on clinical outcomes and left ventricular pressure gradient (LVPG) after ASA. Overall, 120 patients with HOCM who underwent ASA at a single center were divided into two groups based on the presence of optimal ablation. Optimal ablation was defined as the ablated area fully covering the targeted septal myocardium from the point of contact with the onset of the accelerated flow to the basal septum and dense acoustic shadowing accompanying the ablated area. Clinical outcomes and LVPG changes were evaluated using inverse probability of treatment weighting. Significantly more patients showed a New York Heart Association (NYHA) functional class improvement of ≥2 stages or achievement of class I in the optimal ablation group (n = 74) than in the non-optimal ablation group (94 % vs. 62 %; p < 0.001). The optimal ablation group had a significantly greater percentage reduction in LVPG at 1-year after ASA (82 ± 18 % vs. 64 ± 18 %; p = 0.001). Multivariate analyses revealed that optimal ablation was an independent predictor of a NYHA functional class improvement of ≥2 stages or achievement of class I (odds ratio, 11.3; 95 % confidence interval, 3.43-39.1; p < 0.001) and a percentage reduction in LVPG (p = 0.001). Intraprocedural echocardiographic findings of optimal ablation were associated with favorable clinical outcomes and a significant reduction in LVPG.

Normothermic Crystalloid Polarizing Cardioplegia Improves Systolic and Diastolic Function in a Porcine Model of Cardiopulmonary Bypass.

Previously, we showed that blood-based polarizing cardioplegia exerted beneficial cardioprotection during hypothermic ischemia; however, these positive effects of blood-based polarizing cardioplegia were reduced during normothermic ischemia compared to blood-based hyperkalemic (depolarizing) cardioplegia. This study compares crystalloid polarizing cardioplegia to crystalloid depolarizing cardioplegia in a normothermic porcine model of cardiopulmonary bypass; Methods: Twelve pigs were randomized to receive either normothermic polarizing (n = 7) or depolarizing (n = 5) crystalloid cardioplegia. After the initiation of cardiopulmonary bypass, normothermic arrest (34 °C, 60 min) was followed by 60 min of on-pump and 90 min of off-pump reperfusion. Myocardial injury (arterial CK-MB), hemodynamic function, and the energy status of the hearts were measured; Results: The arterial release of CK-MB was comparable between groups (p = 0.78) during reperfusion. During 150 min of reperfusion, systolic left ventricular pressure (p = 0.01) and coronary flow (p = 0.009) were increased, and wedge pressure (p = 0.04) was decreased in the polarized group. Further hemodynamic parameters (cardiac output, stroke volume) and high-energy phosphate levels were similar between groups. The requirement for noradrenaline administration during reperfusion was significantly higher (p = 0.013) in the polarized group; Conclusions: Under normothermic conditions and despite a similar increase in levels of cardiac CK-MB, crystalloid polarizing cardioplegia protected systolic and diastolic cardiac function after 60 min of cardiac arrest. These results suggest beneficial effects for polarizing cardioplegia; clinical studies are required to confirm these effects.