Left Ventricular Pressure Research Articles

Impact of severe secondary tricuspid regurgitation on rest and exercise hemodynamics of patients with heart failure and a preserved left ventricular ejection fraction.

Both secondary tricuspid regurgitation (STR) and heart failure with preserved ejection fraction (HFpEF) are relevant public health problems in the elderly population, presenting with potential overlaps and sharing similar risk factors. However, the impact of severe STR on hemodynamics and cardiorespiratory adaptation to exercise in HFpEF remains to be clarified. To explore the impact of STR on exercise hemodynamics and cardiorespiratory adaptation in HFpEF. We analyzed invasive hemodynamics and gas-exchange data obtained at rest and during exercise from HFpEF patients with severe STR (HFpEF-STR), compared with 1:1 age-, sex-, and body mass index (BMI)- matched HFpEF patients with mild or no STR (HFpEF-controls). Twelve HFpEF with atrial-STR (mean age 72 years, 92% females, BMI 28 Kg/m2) and 12 HFpEF-controls patients were analyzed. HFpEF-STR had higher (p < 0.01) right atrial pressure than HFpEF-controls both at rest (10 ± 1 vs. 5 ± 1 mmHg) and during exercise (23 ± 2 vs. 14 ± 2 mmHg). Despite higher pulmonary artery wedge pressure (PAWP) at rest in HFpEF-STR than in HFpEF-controls (17 ± 2 vs. 11 ± 2, p = 0.04), PAWP at peak exercise was no more different (28 ± 2 vs. 29 ± 2). Left ventricular transmural pressure and cardiac output (CO) increased less in HFpEF-STR than in HFpEF-controls (interaction p-value < 0.05). This latter was due to lower stroke volume (SV) values both at rest (48 ± 9 vs. 77 ± 9 mL, p < 0.05) and at peak exercise (54 ± 10 vs. 93 ± 10 mL, p < 0.05). Despite these differences, the two groups of patients laid on the same oxygen consumption isophlets because of the increased peripheral oxygen extraction in HFpEF-STR (p < 0.01). We found an inverse relationship between pulmonary vascular resistance and SV, both at rest and at peak exercise (R 2 = 0.12 and 0.19, respectively). Severe STR complicating HFpEF impairs SV and CO reserve, leading to pulmonary vascular de-recruitment and relative left heart underfilling, undermining the typical HFpEF pathophysiology.

Glucagon and exenatide improve contractile recovery following ischaemia/reperfusion in the isolated perfused rat heart.

The inotropic effects of glucagon have been recognized for many years, but it has remained unclear whether glucagon signaling is beneficial to cardiac function. We evaluated the effects of glucagon alone and in combination with the glucagon-like peptide 1 (GLP-1) receptor agonist exenatide in the isolated perfused rat heart. The isolated perfused rat heart was used to investigate the initial inotropic and chronotropic effects of glucagon and exenatide during aerobic perfusion, and recovery of contractile function following ischaemia/reperfusion. Glucagon, but not exenatide, elicited an acute chronotropic and inotropic response during aerobic perfusion of the rat heart. Compared with control, glucagon improved recovery of left ventricular developed pressure (LVDP) by 33% (p< 0.05) and rate-pressure product (RPP) by 66% (p< 0.001) following ischaemia/reperfusion and amplified the mild recovery enhancement elicited by exenatide in a dose-dependent manner. Glucagon shows inotropic properties in the isolated perfused rat heart and improves contractile recovery following ischaemia/reperfusion, both alone and when co-administered with a GLP-1 receptor agonist. Glucagon and exenatide, a GLP-1 receptor agonist, combine to stimulate greater recovery of postischaemic contractile function in the Langendorff heart. Glucagon was inotropic and chronotropic, yet this initial effect decreased over time and did not account for the increased contractility observed postischaemia/reperfusion.

Relationship between left atrial myopathy and atrial fibrillation in adults with coarctation of aorta

BackgroundAlthough patients with coarctation of aorta (COA) have clinical risk factors for atrial fibrillation (AF), there are limited data about AF prevalence, and role of left atrial (LA) indices for risk stratification in this population. We hypothesized that LA indices (LA reservoir strain and LA volume index) were associated with AF, and would identify patients at risk for AF progression. MethodsWe analyzed electrocardiograms/Holters, and echocardiograms of adult COA patients at Mayo Clinic (2000–2018). ResultsOf 776 patients, 726(94 %), 46(5.9 %) and 4(0.5 %) had no history of AF, paroxysmal AF, and persistent AF respectively; yielding AF prevalence of 6.4 %. LA reservoir strain (AUC 0.782 [0.751–0.808]) had more robust association with AF as compared to LA volume index (AUC difference −0.115, p < 0.001).Among 726 patients without prior AF, 25(3.4 %) had new-onset AF during follow-up. LA reservoir strain <25 % and LA volume index >34 ml/m2 were independent predictors of new-onset AF (HR 1.81 [1.15–3.85], and HR 1.41 [1.03–4.78], respectively). Of 46 patients with paroxysmal AF, 22(48 %) had recurrent AF, and LA reservoir strain <25 % was an independent predictor of recurrent AF (HR 1.94 [1.41–4.17]). LV pressure overload and stiffness indices were associated with progressive LA dysfunction and new-onset AF. ConclusionsCollectively, these data suggest that LA strain can potentially be used for AF risk stratification. Further studies are required to determine whether LA strain can proactively identify patients that will respond favorably to different antiarrhythmic therapies, and whether interventions to reduce LV pressure overload will improve LA function and reduce AF progression.

Is there any difference in the therapeutic effects of Levosimendan on advanced HFrEF patients with sinus rhythm or atrial fibrillation?

Patients with advanced heart failure have a high incidence of atrial fibrillation (AF) and develop into heart failure with reduced ejection fraction (HFrEF), and require higher doses of inotropes. However, it is uncertain about the differences in the effects of levosimendan in HFrEF patients with sinus rhythm or AF. A total of 63 advanced HFrEF subjects (ejection fraction < 40%) were divided into sinus rhythm (SR, n = 34) and atrial fibrillation (AF, n = 29) cohorts. All patients received six cycles of intermittent repeated levosimendan infusion. After 3 months of treatment, B-type natriuretic peptide (BNP), estimated glomerular filtration rate, resting heart rate (rHR), creatinine, left ventricle ejection fraction (LVEF), left ventricular end diastolic diameter and blood pressure body weight, NYHA classification were measured. After completing the course of treatment, LVEF, BNP, and rHR were significantly decreased (p < 0.0.5), and no significant differences between the two groups were observed (p > 0.05). The NYHA classification improved in the SR group but not in the AF group. There was no significant difference between patients with different rHRs (≤70 bpm vs. >70 bpm) in the SR group (p > 0.05) or in the AF group (rHR ≤ 90 bpm vs. rHR >90 bpm) (p > 0.05). This study showed no difference in the therapeutic effect of intermittent repeated levosimendan infusion on advanced HFrEF with different heart rhythms (SR or AF); Advanced HFrEF patients receive levosimendan treatment without taking the inference of heart rhythm.

Diets Containing Corn Oil, Coconut Oil and Cholesterol Alter Ventricular Hypertrophy, Dilatation and Function in Hearts of Rats Fed Copper-Deficient Diets

Cardiac hypertrophy and function were evaluated in rats fed diets containing deficient, marginal or adequate levels of copper. The fat concentration of the diets was either 10 g/100 g corn oil, 10 g/100 g coconut oil or 10 g/100 g coconut oil + 1 g/100 g added cholesterol. Left ventricular (LV) wall thickening of hearts in rats fed copper-deficient diets was characterized by greater (P < 0.05) LV free wall width, regardless of dietary fat type, and greater intraventricular septum width in the rats fed corn oil. Rats fed the copper-deficient diet with coconut oil + cholesterol had LV chamber volumes that were twofold larger than those of rats fed the copper-deficient diet with coconut oil or corn oil. Copper deficiency reduced LV chamber volume only in rats fed coconut oil + cholesterol. Cardiac LV end diastolic pressure in rats fed copper-deficient diets was twofold larger than in copper-adequate and copper-marginal groups fed corn oil or coconut oil. Hearts from rats fed the copper-deficient diet with corn oil compared with those from rats fed the copper-deficient diet with coconut oil + cholesterol had greater right ventricular (RV) and LV end diastolic pressures, LV pressures and LV and RV maximal rates of positive pressure development. Our data suggest that cardiac adaptations in rats fed copper-deficient diets are influenced by dietary fat type: 1) hearts of rats fed the copper-deficient diet with corn oil were concentrically hypertrophied, whereas cardiac contractility was maintained in the presence of high preload; 2) preload and contractility in hearts of coconut oil-fed rats was greater than cardiac response to cholesterol addition to the coconut oil diet; 3) hearts in copper-deficient rats fed coconut oil + cholesterol exhibited eccentric hypertrophy and ventricular dysfunction.

Impact of Concomitant Mitral Regurgitation on the Hemodynamic Indicators of Aortic Stenosis.

Background In patients with aortic stenosis (AS), the presence of mitral regurgitation (MR) can lead to underestimation of AS severity and worse clinical outcomes. The objective of this study was to characterize the magnitude of the effects of concomitant MR on hemodynamic indicators of AS severity using clinical data and a computational cardiovascular simulation. Methods and Results Echocardiographic data from 1427 patients with severe AS were used to inform a computational cardiovascular system model, and varying degrees of MR and AS were simulated. Hemodynamic data, including left ventricular and aortic pressure waveforms, were generated for all simulations. Simulated reduction in mean transaortic pressure gradient (MPG) associated with MR was then used to calculate the adjusted MPG in the clinical cohort. MR was present in 861 (60%) patients. Compared with patients without MR, patients with MR had a lower aortic-valve area (0.83±0.2 cm2 versus 0.75±0.2; P<0.001) and were more likely to have a low-gradient pattern (MPG <40 mm Hg) (45% versus 54%; P<0.001). Simulations showed that the presence of concomitant mild, moderate, and severe MR with AS was accompanied by a mean reduction in MPG of 10%, 29%, and 40%, respectively. For patients with MR, their calculated adjusted MPG was on average 24% higher than their MPG (52±22 versus 42±16 mm Hg). Of the 467 patients with low-gradient AS and MR, 240 (51%) would reclassify as high gradient based on their adjusted MPG. Conclusions Concomitant MR results in lower MPG and reduced forward flow compared with isolated AS. Careful quantitation of MR should be factored into the assessment of AS severity to mitigate for potential underestimation.

Serial Non-Invasive Myocardial Work Measurements for Patient Risk Stratification and Early Detection of Cancer Therapeutics-Related Cardiac Dysfunction in Breast Cancer Patients: A Single-Centre Observational Study

Serial transthoracic echocardiographic (TTE) assessment of LVEF and GLS are the gold standard in screening Cancer Therapeutics-Related Cardiac Dysfunction (CTRCD). Non-invasive left-ventricle (LV) pressure-strain loop (PSL) emerged as a novel method to quantify Myocardial Work (MW). This study aims to describe the temporal changes and longitudinal trajectories of MW indices during cardiotoxic treatment. We included 50 breast cancer patients with normal LV function referred for anthracycline therapy w/wo Trastuzumab. Medical therapy, clinical and echocardiographic data were recorded before and 3, 6, and 12 months after initiation of the chemotherapy. MW indices were calculated through PSL analysis. According to ESC guidelines, mild and moderated CTRCD was detected in 10 and 9 patients, respectively (20% CTRCDmild, 18% CTRCDmod), while 31 patients remained free of CTRCD (62% CTRCDneg). Prior to chemotherapy MWI, MWE and CW were significantly lower in CTRCDmod than in CTRCDneg and CTRCDmild. Overt cardiac dysfunction in CTRCDmod at 6 months was accompanied by significant worse values in MWI, MWE and WW compared to CTRCDneg and CTRCDmild. MW features such as low baseline CW, especially when associated with a rise in WW at follow-up, may identify patients at risk for CTRCD. Additional studies are needed to explore the role of MW in CRTCD.

Mechanical Control of Relaxation using Intact Cardiac Trabeculae.

Diastolic dysfunction is a common phenotype across cardiovascular disease presentations. In addition to elevated cardiac stiffness (elevated left ventricular end-diastolic pressure), impaired cardiac relaxation is a key diagnostic indicator of diastolic dysfunction. While relaxation requires the removal of cytosolic calcium and deactivation of sarcomeric thin filaments, targeting such mechanisms has yet to provide effective treatments. Mechanical mechanisms, such as blood pressure (i.e., afterload), have been theorized to modify relaxation. Recently, we showed that modifying the strain rate of a stretch, not afterload, was both necessary and sufficient to modify the subsequent relaxation rate of myocardial tissue. The strain rate dependence of relaxation, called the mechanical control of relaxation (MCR), can be assessed using intact cardiac trabeculae. This protocol describes the preparation of a small animal model, experimental system and chamber, isolation of the heart and subsequent isolation of a trabecula, preparation of the experimental chamber, and experimental and analysis protocols. Evidence for lengthening strains in the intact heart suggests that MCR might provide new arenas for better characterization of pharmacological treatments, along with a method to assess myofilament kinetics in intact muscles. Therefore, studying the MCR may elucidate a path to novel approaches and new frontiers in the treatment of heart failure.

Endothelio- and cardioprotective effects of vitamin в6 and folic acid in modelling methionine-induced hyperhomocysteinemia

The endotelio- and cardioprotective effects of vitamin B6 (2 mg/kg) and folic acid (0.2 mg/kg) upon modeling of methionine-induced hyperhomocysteinemia via methionine intragastric administration at a dose of 3 g/kg were studied. It was shown that the combined use of vitamin B6 and folic acid allows on the background of a significant reduction in homocysteine concentrations normalizing the endothelial dysfunction coefficient and the parameters of maximum left ventricular pressure in response to intravenous administration of adrenaline. The research was partially supported by the grant of the President of the Russian Federation №MD-4711.2015.7.

Downregulation of microRNA-23a confers protection against myocardial ischemia/reperfusion injury by upregulating tissue factor pathway inhibitor 2 following luteolin pretreatment in rats.

Downregulation of microRNA-23a confers protection against myocardial ischemia/reperfusion injury by upregulating tissue factor pathway inhibitor 2 following luteolin pretreatment in rats.

Time domain adaptation of left ventricular diastolic intraventricular pressure in elite female ice hockey athletes.

Ice hockey is a high-intensity dynamic sport for which competitive athletes train for longer than 20 hours each week for several years. The cumulative time of myocardial exposure to hemodynamic stress affects cardiac remodeling. However, the intracardiac pressure distribution of the elite ice hockey athletes' heart during adaptation to long-term training remains to be explored. This study aimed to compare the diastolic intraventricular pressure difference (IVPD) of the left ventricle (LV) between healthy volunteers and ice hockey athletes with different training times. Fifty-three female ice hockey athletes (27 elite and 26 casual) and 24 healthy controls were included. The diastolic IVPD of the LV during diastole was measured by vector flow mapping. The peak amplitude of the IVPD during isovolumic relaxation (P0), diastolic rapid filling (P1), and atrial systole (P4); the difference in the peak amplitude between adjacent phases (DiffP01, DiffP14); the time interval between the peak amplitude of adjacent phases (P0P1, P1P4); and the maximum decrease rate in diastolic IVPD were calculated. Differences between groups, as well as correlations between hemodynamic parameters and training time, were analyzed. Structural parameters of the LV were significantly higher in elite athletes than in casual players and controls. No significant difference in the peak amplitude of the IVPD during the diastolic phase was found among the three groups. The analysis of covariance with heart rate as a covariate showed that P1P4 in the elite athlete and casual player groups was significantly longer than that in the healthy control group (p < 0.001 for all). An increased P1P4 was significantly associated with an increased training year (β = 4.90, p < 0.001). The diastolic cardiac hemodynamics of the LV in elite female ice hockey athletes could be characterized by a prolonged diastolic IVPD, and P1P4 prolonged with an increase in the training years, reflecting a time-domain adaptation in diastolic hemodynamics after long-term training.

Effects of T3 Administration on Ex Vivo Rat Hearts Subjected to Normothermic Perfusion: Therapeutic Implications in Donor Heart Preservation and Repair.

The present study investigated the effects of triiodothyronine (T3) administration in ex vivo model of rat heart normothermic perfusion. T3 is cardioprotective and has the potential to repair the injured myocardium. Isolated hearts were subjected to normothermic perfusion (NP) with Krebs-Henseleit for 4h with vehicle (NP) or 60nM T3 in the perfusate (NP + T3). Left ventricular end diastolic pressure (LVEDP), left ventricular developed pressure (LVDP), perfusion pressure (PP) and percentage of change of these parameters from the baseline values were measured. Activation of stress induced kinase signaling was assessed in tissue samples. Baseline parameters were similar between groups. LVEDP was increased from the baseline by 13% (70) for NP + T3 vs. 139% (160) for NP group, p = 0.048. LVDP was reduced by 18.2% (5) for NP + T3 vs. 25.3% (19) for NP group, p = 0.01. PP was increased by 41% (19) for NP + T3 vs.91% (56) for NP group, p = 0.024. T3 increased activation of pro-survival Akt by 1.85 fold (p = 0.047) and AMPK by 2.25 fold (p = 0.01) and reduced activation of pro-apoptotic p38 MAPK by 3fold (p = 0.04) and p54 JNK by 4.0 fold (p = 0.04). Administration of T3 in normothermic perfusion had favorable effects on cardiac function and perfusion pressure and switched death to pro-survival kinase signaling.

Pulse arrival time variation as a non-invasive marker of acute response to cardiac resynchronization therapy.

Successful cardiac resynchronization therapy (CRT) shortens the pre-ejection period (PEP) which is prolonged in the left bundle branch block (LBBB). In a combined animal and patient study, we investigated if changes in the pulse arrival time (PAT) could be used to measure acute changes in PEP during CRT implantation and hence be used to evaluate acute CRT response non-invasively and in real time. In six canines, a pulse transducer was attached to a lower limb and PAT was measured together with left ventricular (LV) pressure by micromanometer at baseline, after induction of LBBB and during biventricular pacing. Time-to-peak LV dP/dt (Td) was used as a surrogate for PEP. In twelve LBBB patients during implantation of CRT, LV and femoral pressures were measured at baseline and during five different pacing configurations. PAT increased from baseline (277 ± 9 ms) to LBBB (313 ± 16 ms, P < 0.05) and shortened with biventricular pacing (290 ± 16 ms, P < 0.05) in animals. There was a strong relationship between changes in PAT and Td in patients (r2 = 0.91). Two patients were classified as non-responders at 6 months follow-up. CRT decreased PAT from 320 ± 41 to 298 ± 39 ms (P < 0.05) in the responders, while PAT increased by 5 and 8 ms in the two non-responders. This proof-of-concept study indicates that PAT can be used as a simple, non-invasive method to assess the acute effects of CRT in real time with the potential to identify long-term response in patients.

Dynamic pressure–volume loop analysis by simultaneous real-time cardiovascular magnetic resonance and left heart catheterization

BackgroundLeft ventricular (LV) contractility and compliance are derived from pressure–volume (PV) loops during dynamic preload reduction, but reliable simultaneous measurements of pressure and volume are challenging with current technologies. We have developed a method to quantify contractility and compliance from PV loops during a dynamic preload reduction using simultaneous measurements of volume from real-time cardiovascular magnetic resonance (CMR) and invasive LV pressures with CMR-specific signal conditioning. MethodsDynamic PV loops were derived in 16 swine (n = 7 naïve, n = 6 with aortic banding to increase afterload, n = 3 with ischemic cardiomyopathy) while occluding the inferior vena cava (IVC). Occlusion was performed simultaneously with the acquisition of dynamic LV volume from long-axis real-time CMR at 0.55 T, and recordings of invasive LV and aortic pressures, electrocardiogram, and CMR gradient waveforms. PV loops were derived by synchronizing pressure and volume measurements. Linear regression of end-systolic- and end-diastolic- pressure–volume relationships enabled calculation of contractility. PV loops measurements in the CMR environment were compared to conductance PV loop catheter measurements in 5 animals. Long-axis 2D LV volumes were validated with short-axis-stack images. ResultsSimultaneous PV acquisition during IVC-occlusion was feasible. The cardiomyopathy model measured lower contractility (0.2 ± 0.1 mmHg/ml vs 0.6 ± 0.2 mmHg/ml) and increased compliance (12.0 ± 2.1 ml/mmHg vs 4.9 ± 1.1 ml/mmHg) compared to naïve animals. The pressure gradient across the aortic band was not clinically significant (10 ± 6 mmHg). Correspondingly, no differences were found between the naïve and banded pigs. Long-axis and short-axis LV volumes agreed well (difference 8.2 ± 14.5 ml at end-diastole, -2.8 ± 6.5 ml at end-systole). Agreement in contractility and compliance derived from conductance PV loop catheters and in the CMR environment was modest (intraclass correlation coefficient 0.56 and 0.44, respectively). ConclusionsDynamic PV loops during a real-time CMR-guided preload reduction can be used to derive quantitative metrics of contractility and compliance, and provided more reliable volumetric measurements than conductance PV loop catheters.

Left Ventricular Filling Pressure in Chronic Thromboembolic Pulmonary Hypertension

BackgroundChronic thromboembolic pulmonary hypertension (CTEPH) is characterized by obstruction of major pulmonary arteries with organized thrombi. Clinical risk factors for pulmonary hypertension due to left heart disease including metabolic syndrome, left-sided valvular heart disease, and ischemic heart disease are common in CTEPH patients. ObjectivesThe authors sought to investigate prevalence and prognostic implications of elevated left ventricular filling pressures (LVFP) in CTEPH. MethodsA total of 593 consecutive CTEPH patients undergoing a first diagnostic right and left heart catheterization were included in this study. Mean pulmonary arterial wedge pressure (mPAWP) and left ventricular end-diastolic pressure (LVEDP) were utilized for assessment of LVFP. Two cutoffs were applied to identify patients with elevated LVFP: 1) for the primary analysis mPAWP and/or LVEDP >15 mm Hg, as recommended by the current pulmonary hypertension guidelines; and 2) for the secondary analysis mPAWP and/or LVEDP >11 mm Hg, representing the upper limit of normal. Clinical and echocardiographic features, and long-term mortality were assessed. ResultsLVFP was >15 mm Hg in 63 (10.6%) and >11 mm Hg in 222 patients (37.4%). Univariable logistic regression analysis identified age, systemic hypertension, diabetes, atrial fibrillation, calcific aortic valve stenosis, mitral regurgitation, and left atrial volume as significant predictors of elevated LVFP. Atrial fibrillation, calcific aortic valve stenosis, mitral regurgitation, and left atrial volume remained independent determinants of LVFP in adjusted analysis. At follow-up, higher LVFPs were measured in patients who had meanwhile undergone pulmonary endarterectomy (P = 0.002). LVFP >15 mm Hg (P = 0.021) and >11 mm Hg (P = 0.006) were both associated with worse long-term survival. ConclusionsElevated LVFP is common, appears to be due to comorbid left heart disease, and predicts prognosis in CTEPH.

Abstract WP182: Diastolic Dysfunction With Elevated Left Ventricular Filling Pressures Is Associated With Embolic Stroke Of Undetermined Source And Atrial Fibrillation Detection After Ischemic Stroke

Introduction: Diastolic dysfunction, particularly with elevated left ventricle filling pressure (LVFP) is known to be a strong independent predictor of all-cause mortality and major cardiac events. There is limited data on the role of diastolic function in ischemic stroke. We hypothesize that diastolic dysfunction with elevated LVFP is more likely to be present in patients with Embolic stroke of undetermined source (ESUS) compared to non-cardioembolic stroke and is associated with AF on cardiac monitoring in the ESUS group. Methods: This is a single center retrospective study that included adult patients with a diagnosis of acute ischemic stroke from 2014 to 2016. We excluded patients with confirmed cardioembolic stroke and those with indeterminate diastolic function. ESUS was defined as no ipsilateral stenoses ≥ 50%, cardiac telemetry for at least two weeks without evidence of atrial fibrillation or atrial flutter, and a LVEF ≥ 30%. A transthoracic echocardiogram was performed and interpreted by cardiologists. Baseline patient characteristics and clinical variables were compared among patients with and without diastolic dysfunction. Potential associations between diastolic dysfunction, ESUS and AF detection in ESUS patients were assessed using logistic regression. Results: There were 509 patients, the mean age was 64.19, 54.81% were male, and 146 had LVFP data. Diastolic dysfunction overall was not associated with ESUS (adjusted OR 1.44, 95% CI 0.91-2.28, p = 0.125) or AF detection on cardiac monitoring (adjusted OR 1.87, 95% CI 0.75-4.70, p = 0.183). However, diastolic dysfunction and elevated LVFP was associated with ESUS subtype (adjusted OR 2.26, 95% CI 1.03-4.93, p = 0.041) and AF detection on cardiac monitoring (adjusted OR 3.58, 95% CI 1.07-12.01, p = 0.039). Conclusion: Our study suggests that diastolic dysfunction with elevated LVFP is associated with ESUS stroke subtype and AF detection on cardiac monitoring. Therefore, the presence of diastolic dysfunction with elevated LVFP may identify a population of stroke patients more likely to have ESUS, particularly in the setting of occult AF. Studies are needed to confirm our findings and test the safety and efficacy of anticoagulation in patients with ESUS and diastolic dysfunction with elevated LVFP.

Hemodynamic impairment induced by Crotoxin using in vivo and ex vivo approach in a rat model

Crotalus durissus snakebite represent 10 % of snakebite cases in Brazil, which cardiovascular disorders are associated with severe cases. Considering crotoxin (CTX) as the major venom component, the present study aimed to evaluate the hemodynamic alterations induced by CTX using in vivo and ex vivo approaches in a rat model. In vivo cardiac function parameters were analyzed from anesthetized rats treated with CTX or saline only (Sham), along with serum creatine kinase MB (CK-MB) and lung myeloperoxidase. From the same animals, hearts were isolated and functional parameters evaluated in Langendorff method ex vivo. CTX binding to myoblast cell line in vitro were evaluated using confocal microscopy and flow cytometry. CTX was capable of reducing arterial and diastolic blood pressure, heart rate, along with left ventricle pressure development or decay during systole (LVdP/dtmax and LVdP/dtmin) in vivo, however no differences were found in the ex vivo approach, showing that intrinsic heart function was preserved. In vitro, CTX binding to myoblast cell line was mitigated by hexamethonium, a nicotinic acetylcholine receptor antagonist. The present study has shown that CTX induce hemodynamic failure in rats, which can help improve the clinical management of cardiovascular alterations during Crotalus durissus snakebite.

Factors associated with morbidity, mortality, and hemodynamic failure after biventricular conversion in borderline hypoplastic left hearts

ObjectiveA subset of patients with borderline hypoplastic left heart may be candidates for single to biventricular conversion, but long-term morbidity and mortality persist. Prior studies have shown conflicting results regarding the association of preoperative diastolic dysfunction and outcome, and patient selection remains challenging. MethodsPatients with borderline hypoplastic left heart undergoing biventricular conversion from 2005 to 2017 were included. Cox regression identified preoperative factors associated with a composite outcome of time to mortality, heart transplant, takedown to single ventricle circulation, or hemodynamic failure (defined as left ventricular end-diastolic pressure >20 mm Hg, mean pulmonary artery pressure >35 mm Hg, or pulmonary vascular resistance >6 international Woods units). ResultsAmong 43 patients, 20 (46%) met the outcome, with a median time to outcome of 5.2 years. On univariate analysis, endocardial fibroelastosis, lower left ventricular end-diastolic volume/body surface area (when <50 mL/m2), lower left ventricular stroke volume/body surface area (when <32 mL/m2), and lower left:right ventricular stroke volume ratio (when <0.7) were associated with outcome; higher preoperative left ventricular end-diastolic pressure was not. Multivariable analysis demonstrated that endocardial fibroelastosis (hazard ratio, 5.1, 95% confidence interval, 1.5-22.7, P = .033) and left ventricular stroke volume/body surface area 28 mL/m2 or less (hazard ratio, 4.3, 95% confidence interval, 1.5-12.3, P = .006) were independently associated with a higher hazard of the outcome. Approximately all patients (86%) with endocardial fibroelastosis and left ventricular stroke volume/body surface area 28 mL/m2 or less met the outcome compared with 10% of those without endocardial fibroelastosis and with higher stroke volume/body surface area. ConclusionsHistory of endocardial fibroelastosis and smaller left ventricular stroke volume/body surface area are independent factors associated with adverse outcomes among patients with borderline hypoplastic left heart undergoing biventricular conversion. Normal preoperative left ventricular end-diastolic pressure is insufficient to reassure against diastolic dysfunction after biventricular conversion.

Echocardiographic reference ranges for noninvasive left ventricular 18-segment myocardial work index and work efficiency in a healthy Asian population

BackgroundLeft ventricular (LV) myocardial work index (WI) and work efficiency (WE) have become the latest indicators for assessing LV function. Reference ranges for normal LV segmental WI and WE have not been established.MethodsFour hundred eleven healthy Asian subjects (47% men, median age: 35 years) were enrolled prospectively. WI and WE were analysed using the LV pressure–strain loop (LVPSL) with specific software.ResultsWI and WE differed significantly between segments as well as between walls and levels of the left ventricle. The anteroseptal basal segment had the lowest WI and WE (1440 mmHg ± 324 and 92% [88–96], respectively) among the eighteen segments. Significant WI and WE differences were found between sexes and age groups. No correlation was observed between age groups and the average WI of any wall or level in men, while the average WI of several different walls and levels in women showed significant differences between age groups. The average WI of most walls and levels increased with age in women. No correlation was found between age groups and the average WE of any wall or level in either men or women.ConclusionsThis study establishes the normal reference values of WI and WE of eighteen segments for clinical work and clinical experiments. There were significant differences in WI and WE between segments, levels, and walls of the normal left ventricle. Sex should be considered when analysing WI and WE. Age should be considered when analysing WI in women.Graphical

O-Linked Glycans of Candida albicans Interact with Specific GPCRs in the Coronary Endothelium and Inhibit the Cardiac Response to Agonists

Candida albicans is an opportunistic fungal pathogen that may cause invasive infections in immunocompromised patients, disseminating through the bloodstream to other organs. In the heart, the initial step prior to invasion is the adhesion of the fungus to endothelial cells. Being the fungal cell wall's outermost structure and the first to come in contact with host cells, it greatly modulates the interplay that later will derive in the colonization of the host tissue. In this work, we studied the functional contribution of N-linked and O-linked mannans of the cell wall of C. albicans to the interaction with the coronary endothelium. An isolated rat heart model was used to assess cardiac parameters related to vascular and inotropic effects in response to phenylephrine (Phe), acetylcholine (aCh) and angiotensin II (Ang II) when treatments consisting of: (1) live and heat-killed (HK) C. albicans wild-type yeasts; (2) live C. albicans pmr1Δ yeasts (displaying shorter N-linked and O-linked mannans); (3) live C. albicans without N-linked and O-linked mannans; and (4) isolated N-linked and O-linked mannans were administered to the heart. Our results showed that C. albicans WT alters heart coronary perfusion pressure (vascular effect) and left ventricular pressure (inotropic effect) parameters in response to Phe and Ang II but not aCh, and these effects can be reversed by mannose. Similar results were observed when isolated cell walls, live C. albicans without N-linked mannans or isolated O-linked mannans were perfused into the heart. In contrast, C. albicans HK, C. albicans pmr1Δ, C. albicans without O-linked mannans or isolated N-linked mannans were not able to alter the CPP and LVP in response to the same agonists. Taken together, our data suggest that C. albicans interaction occurs with specific receptors on coronary endothelium and that O-linked mannan contributes to a greater extent to this interaction. Further studies are necessary to elucidate why specific receptors preferentially interact with this fungal cell wall structure.