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This study evaluated the effects of extracorporeal membrane oxygenation (ECMO) in combination with a percutaneous adjunctive left ventricular assist device (LVAD) in a porcine model during 60 minutes of refractory cardiac arrest (CA). Twenty-four anesthetized swine were randomly allocated into three groups given different modes of circulatory assist: group 1: ECMO 72 ml/kg/min and LVAD; group 2: ECMO 36 ml/kg/min and LVAD; and group 3: ECMO 72 ml/kg/min. During CA and extracorporeal cardiopulmonary resuscitation (ECPR), mean left ventricular pressure (mLVP) was lower in group 1 (p = 0.013) and in group 2 (p = 0.003) versus group 3. Mean aortic pressure (mAP) and coronary perfusion pressure (CPP) were higher in group 1 compared with the other groups. In group 3, mean pulmonary artery flow (mPAf) was lower versus group 1 (p = 0.003) and group 2 (p = 0.039). If the return of spontaneous circulation (ROSC) was achieved after defibrillation, up to 180 minutes of unsupported observation followed. All subjects in groups 1 and 3, and 5 subjects in group 2 had ROSC. All subjects in group 1, five in group 2 and four in group 3 had sustained cardiac function after 3 hours of spontaneous circulation. Subjects that did not achieve ROSC or maintained cardiac function post-ROSC had lower mAP (p < 0.001), CPP (p= 0.002), and mPAf (p = 0.004) during CA and ECPR. Add-on LVAD may improve hemodynamics compared with ECMO alone during refractory CA but could not substitute reduced ECMO flow. Increased mAP and CPP could be related to ROSC rate and sustained cardiac function. Increased mLVP was related to poor post-ROSC cardiac function.

Catheter ablation is the most effective rhythm control method for patients with atrial fibrillation (AF); however, it inevitably causes atrial tissue damage. We previously reported that AF catheter ablation (AFCA) increases left atrial (LA) pressure without changes in symptom scores. We hypothesized that extensive LA ablation increased the risk of stiff LA physiology. We included 1,720 patients (69.1% male, 60.0 [53.0–68.0] years old, 66.2% with paroxysmal AF) who underwent de novo AFCA and echocardiography before and 1-year after the procedure. Stiff LA physiology was defined, when the amount of the estimated pulmonary arterial pressure increase between the pre-procedural and the 1-year post-procedural follow-up echocardiography was >10 mmHg and when right ventricular systolic pressure (RVSP) was >35 mmHg at 1-year follow-up echocardiography. The failed rhythm control within 1 year was defined as recurrent AF despite using anti-arrhythmic drugs or cardioversion within a year of AFCA. We explored the incidence and risk factors for stiff LA physiology and the rhythm outcome of AFCA. Among the 1,720 patients, 64 (3.7%) had stiff LA physiology 1 year after AFCA. Stiff LA physiology was independently associated with diabetes (odds ratio [OR], 2.36 [95% CI, 1.14–4.87], p = 0.020), the ratio of the peak mitral flow velocity of the early rapid filling to the early diastolic velocity of the mitral annulus (E/Em; OR, 1.04 [95% CI, 1.00–1.10], p = 0.049), LA pulse pressure (Model 2: OR, 1.05 [95% CI, 1.00–1.11], p = 0.049), low LA voltage (OR, 0.36 [95% CI, 0.18–0.74], p = 0.005), empirical extra-pulmonary vein (PV) LA ablation (OR, 2.60 [95% CI, 1.17–5.74], p = 0.018), and radiofrequency (RF) ablation duration (Model 2: OR, 1.02 [95% CI, 1.01–1.03], p = 0.003). Although the incidence of post-AFCA stiff LA physiology was 3.7% and most of the cases were subclinical, the empirical extra-PV ablation was associated with this undesirable condition. In addition, patients who had low mean LA voltage before AFCA could be susceptible to stiff LA physiology.

Cardiopulmonary sympathetic control is exerted via stellate ganglia (SG); however, little is known about how neuronal firing patterns in the stellate ganglion relate to dynamic physiological function in the heart and lungs. We performed continuous extracellular recordings from SG neurons using multielectrode arrays in chloralose-anesthetized pigs (n = 6) for 8–9 h. Respiratory and left ventricular pressures (RP and LVP, respectively) and the electrocardiogram (ECG) were recorded concomitantly. Linkages between sampled spikes and LVP or RP were determined using a novel metric to evaluate specificity in neural activity for phases of the cardiac and pulmonary cycles during resting conditions and under various cardiopulmonary stressors. Firing frequency (mean 4.6 ± 1.2 Hz) varied spatially across the stellate ganglion, suggesting regional processing. The firing pattern of most neurons was synchronized with both cardiac (LVP) and pulmonary (RP) activity indicative of cardiopulmonary integration. Using the novel metric to determine cardiac phase specificity of neuronal activity, we found that spike density was highest during diastole and near-peak systole. This specificity was independent of the actual LVP or population firing frequency as revealed by perturbations to the LVP. The observed specificity was weaker for RP. Stellate ganglion neuronal populations exhibit cardiopulmonary integration and profound specificity toward the near-peak systolic phase of the cardiac cycle. This novel approach provides practically deployable tools to probe stellate ganglion function and its relationship to cardiopulmonary pathophysiology. NEW & NOTEWORTHY Activity of stellate ganglion neurons is often linking indirectly to cardiac function. Using novel approaches coupled with extended period of recordings in large animals, we link neuronal population dynamics to mechanical events occurring at near-peak systole. This metric can be deployed to probe stellate ganglion neuronal control of cardiopulmonary function in normal and disease states.

Despite its negative effect on the cardiovascular system, waterpipe smoking (WPS) is currently popular worldwide, especially among youth. This study investigated the effects of moderate endurance exercise on heart function of rats exposed to WPS and its possible mechanism. The animals were randomly divided into four groups: control group (CTL), the exercise group (Ex) which trained for 8 weeks, the waterpipe tobacco smoking group (S) exposed to smoke inhalation (30 min per day, 5 days each week, for 8 weeks), and the group that did exercise training and received waterpipe tobacco smoke inhalation together (Ex + S). One day after the last session of Ex and WPS, cardiac pressures and functional indices were recorded and calculated. The levels of SIRT1, SIRT3, Klotho, Bax, and Bcl-2 in the serum and heart, the expression of phosphorylated GSK3β of heart tissue, and cardiac histopathological changes were assessed. WPS reduced systolic pressure, +dP/dt max, -dP/dt max, and heart contractility indices (P < 0.001 vs. CTL) and increased cardiac tissue lesions (P < 0.05 vs. CTL) and end diastolic pressure and Tau index (P < 0.001 vs. CTL) of the left ventricle. Exercise training normalized the left ventricular end diastolic pressure, +dP/dt max, and contractility index. Also, exercise improved the levels of SIRT1, SIRT3, Klotho, and Bcl-2 and reduced Bax level in the heart. The findings showed that WPS causes left ventricular dysfunction. Moderate exercise prevented WPS-induced heart dysfunction partly through its anti-apoptotic features and activation of the sirtuins and Klotho pathways.

International audience; When combining cardiovascular magnetic resonance imaging (CMR) with pressure catheter measurements, the acquired imageand pressure data need to be synchronized in time. The time offset between the image and pressure data depends on a number of factors,such as the type and settings of the MR sequence, duration and shape of QRS complex or the type of catheter, and cannot be typically estimated beforehand. In the present work we propose using a biophysical heart model to synchronize the left ventricular (LV) pressure and volume (P-V) data. Ten patients, who underwent CMR and LV catheterization, were included. A biophysical model of reduced geometrical complexity with physiologically substantiated timing of each phase of the cardiac cycle was first adjusted to individual patients using basic morphological and functional indicators. The pressure and volume waveforms simulated by the patient-specific models were then used as templates to detect the time offset between the acquired ventricular pressure and volume waveforms. Time-varying ventricular elastance was derived from clinical data both as originally acquired as well as when time-synchronized, and normalized with respect to end-systolic time and maximum elastance value$E^N_\text {orig}(t)$, $E^N_\text {t-syn}(t)$, respectively). $E^N_\text {t-syn}(t)$ was significantly closer to the experimentally obtained $E^N_\text {exp}(t)$ published in the literature (p < 0.05, $L^2$ norm). The work concludes that the model-driven time-synchronization of P-V data obtained by catheter measurement and CMR allows to generate high quality P-V loops, which can then be used for clinical interpretation.

Background: Previously, we invented a therapeutic vaccine targeting the endothelin-A receptor (termed ETRQβ-002). ETRQβ-002 successfully prevented the remodeling of pulmonary arterioles (PAs) and right ventricle (RV) without significant immune-mediated damage in experimental pulmonary arterial hypertension (PAH) mice models.Objective: Here, we aim to further evaluate the long-term effects of ETRQβ-002.Methods: PAH mice model was induced by a combination of subcutaneous injection with Sugen5416 and chronic hypoxic conditions (10% O2). PAH mice were immunized with ETRQβ-002 at different time points, and the experiment lasted for 21 weeks. Hemodynamic, histological, and biochemical analyses were conducted to evaluate the long-term effects of ETRQβ-002.Results: We demonstrated that the titer of the specific antibody against ETR-002 could be maintained chronically after periodic booster immunization in PAH mice. Long-term reduction of right ventricular systolic pressure and amelioration of PA remodeling by ETRQβ-002 were confirmed. Moreover, we found that ETRQβ-002 also exerted antiproliferation, anti-inflammation, and antifibrosis effects in PA remodeling. Besides, ETRQβ-002 durably limited pathological RV hypertrophy and fibrosis. Finally, no immune-mediated damage was observed in hepatic or renal function or by pathology in liver and kidney during the long-term administration of ETRQβ-002.Conclusion: Our findings indicate that ETRQβ-002 provides long-term therapeutic effects in Sugen/hypoxia-induced PAH animals and offers a promising clinical prospect for PAH treatment.

BACKGROUND. Given the risk of hemodynamic compromise in heart failure with reduced ejection fraction (HFrEF) patients undergoing left heart catheterization (LHC), there is a need for a simple parameter that can predict clinical outcomes. We hypothesize that left ventricular pressure ratio (LVPR), calculated as left ventricle systolic/left ventricle end-diastolic pressure, is a strong predictor of hemodynamic collapse in these patients. METHODS. Retrospective analysis of consecutive hospitalized HFrEF patients undergoing combined LHC and right heart catheterization (RHC) at a single institution from 2015–2017 was performed. LVPR was compared with standard RHC hemodynamic variables. The primary outcome was in-hospital escalation of therapy, defined as ≥40 mm Hg drop in systolic blood pressure (SBP), SBP ≤90 mm Hg for ≥15 minutes, start or escalation of vasoactive medications, cardiopulmonary resuscitation, or in-hospital death. Receiver-operating characteristic (ROC) analysis and Kaplan-Meier survival analysis were performed for prediction of the primary outcome. RESULTS. A total of 176 patients were included in this study. ROC analysis determined an optimal cut-off value of ≤3.96, which correlated with an area under the curve (AUC) of 0.65 (sensitivity, 45.9%; specificity, 83.2%; correctly classified, 64.9%). AUC was similar to other variables obtained using RHC. In-hospital survival free of escalation of therapy was lower in the low LVPR group vs the high LVPR group (0% vs 33%, respectively; P

Patient-reported outcomes are important metrics of medical and surgical care. In this study, we investigated the prevalence and risk factors of patient-reported postdischarge atrial fibrillation (AF) after septal myectomy for obstructive hypertrophic cardiomyopathy.Patients undergoing transaortic septal myectomy from August 2001 to January 2017 were contacted regarding postdischarge AF through questionnaire-based surveys sent at 3, 5, and 10 years post procedure. For each patient, the most recent survey response was analyzed.Among 949 patients, 248 (26.1%) last responded at 3 years post procedure, 353 (37.2%) at 5 years, and 348 (36.7%) at 10 years. The overall incidence of patient-reported postdischarge AF was 34.4% (n = 326), and at 3, 5, and 10 years, the incidences were 22.2%, 34.8%, and 42.5% (P.001). After multivariable adjustment, history of preoperative AF (odds ratio [OR] 5.566, P.001), early postoperative AF within the first 30 days (OR 2.211, P.001), preoperative left atrial volume index (OR 1.014, P = .005), postoperative right ventricular systolic pressure (OR 1.021, P = .013), postoperative moderate or greater mitral valve regurgitation (OR 1.893, P = .022), and preoperative septal thickness (OR 1.043, P = .036) were independently associated with patient-reported postdischarge AF.The incidence of patient-reported postdischarge AF increases with increasing length of follow-up after septal myectomy. We identified several risk factors for late postdischarge AF that were associated with chronicity of left ventricular outflow tract obstruction, and earlier intervention may mitigate late atrial arrhythmias.

Purposes: The purposes of this study were to use noninvasive Left ventricular pressure-strain loops (LV-PSLs) to compare the various myocardial work indices in patients with noninvasive hypertrophic cardiomyopathy (NHCM) and to evaluate the clinical application of myocardial work to the evaluation of NHCM patients.Method: 80 NHCM patients and 45 healthy subjects were enrolled. All the selectors underwent Echocardiography examination. Dynamic images of standard apical three-chamber, four-chamber, and two-chamber view were collected, the myocardial work indices of left ventricle were measured by LV-PSLs. The difference in myocardial work indices between two groups and various myocardial work indices in different types of hypertrophic cardiomyopathy were compared.Results: There were no significant difference in the general clinical data between the NHCM group and control; myocardial work indices of HCM were lower compared with control group except global work waste (GWW); The myocardial work between all three types of NHCMs was also different, particularly in global construction work (GCW); the intra- and inter observer consistency of myocardial work indices were good.Conclusion: Myocardial work assessed by the LV-PSLs could reflect myocardial work in NHCM patients at the early stage and quantitatively assess regional and global myocardial function, providing an accurate and convenient imaging method for early detection of the subclinical status of NHCM patients.

We report on an 8-year-old boy, who presented to the emergency department at our institution with fever, generalised oedema and hypotension. Investigations revealed anaemia, thrombocytopenia in addition to elevated serum inflammatory markers, a negative COVID-19 PCR test and a positive COVID-19 IgG. His echocardiography was consistent with carditis in otherwise morphologically normal heart with depressed cardiac function, moderate-to-severe mitral valve regurgitation, moderate tricuspid regurgitation with an estimated right ventricular systolic pressure half systemic, trace aortic regurgitation, bilateral small pleural effusions, distended inferior vena cava and normal coronaries. He was started on inotropic support, intravenous immunoglobulin and methylprednisolone, and was transferred to the paediatric intensive care unit. To the best of our knowledge, this was the first case of multisystem inflammatory syndrome in children encountered in Lebanon. The presentation and management were thoroughly described in this article aiming to share our experience and to contribute to the rapidly emerging literature on this syndrome.

Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): JSPS KAKENHI, Grant-in-Aid for Early-Career Scientists. Background Pulmonary arterial hypertension (PAH) remains a fatal disorder characterized by elevated pulmonary arterial pressure. Survival of the patients with PAH is determined from right ventricular (RV) function. CMR has become an attractive modality for following up and providing prognosis in such patients, and CMR feature tracking has been used as a newer useful parameter to assess RV function. However, it has not yet been determined whether CMR feature tracking can assess RV functional reserve in patients with PAH. Purpose We investigated whether CMR feature tracking can estimate RV functional reserve using a rat model with PAH. Methods Rats were received injections with monocrotaline (MCT-rats, n = 19) or solvent (Ctr-rats, n = 5). Four weeks after the injections, we performed CMR on 7-T MRI scanner and imaged retrospective ECG-gated cine MR (16 phases/beat). RV ejection fraction (RVEF) and RV strain were analyzed before and after addition of 0.5∼3 nmol endothelin-1 (ET-1). After the measurements, we dissected trabeculae (length = 1.45 ± 0.07 mm, width = 334 ± 27 µm, thickness = 114 ± 6 µm) from the RVs of rat hearts. Trabeculae were electrically stimulated with 2-s intervals at extracellular Ca2+ of 0.7 and 2.0 mmol/L (24°C). Force and maximum dF/dt (dF/dtmax) were then measured using a silicon strain gauge in the absence and presence of 0.1 µM ET-1. Results MCT-rats showed higher systolic RV pressure (RVP), lower RVEF, and lower RV global longitudinal strain (RVGLS) in CMR imaging and showed lower developed force and lower dF/dtmax in their trabeculae. Correlation between RVGLS and dF/dtmax was higher (r = 0.53, p 50%), RVGLS had already been reduced, suggesting that RVGLS is reduced earlier than RVEF. ET-1 increased developed force and dF/dtmax in trabeculae from MCT-rats (12.2 ± 5.7 to 17.4 ± 3.1 mN/mm2 and 0.08 ± 0.03 to 0.14 ± 0.06 mN/mm2/sec, respectively, n = 6), and ET-1 also increased RVP in MCT-rats and Ctr-rats (49.0 ± 19.3 to 59.7 ± 16.8 mmHg in MCT-rats, n = 6, 17.3 ± 7.5 to 20.4 ± 7.8 mmHg in Ctr-rats, n = 2). According to RV global circumferential strain (RVGCS) and RVEF, we could divide MCT-rats into three groups as follows: MCT-rats with reduced-RVGCS (> -20%)/preserved-RVEF (> 50%), MCT-rats with increased-RVGCS (< -30%)/preserved-RVEF and MCT-rats with reduced-RVGCS/reduced-RVEF. ET-1 reduced RVGCS in MCT-rats with reduced-RVGCS/preserved-RVEF, while ET-1 did not change RVGCS in MCT-rats with increased-RVGCS/preserved-RVEF. MCT-rats with reduced-RVGCS/reduced-RVEF died after injection of ET-1. In Ctr-rats, ET-1 did not change RVGCS and RVEF. These results suggest that RVGCS can be useful to assess RV functional reserve. Conclusion CMR feature tracking can estimate RV functional reserve earlier and more accurately than RVEF in rats with PAH. RV strain may become an important parameter to assess RV functional reserve in patients with PAH.

In this issue of The Journal , Quinn, et al describe the utility of exercise echocardiography (EE) in the identification of patients with systemic sclerosis (SSc) deemed high risk for the development of pulmonary arterial hypertension (PAH)1. In a single-center observational study, the authors demonstrated that a significantly higher percentage of SSc patients with a persistently positive EE, as defined by an increase in right ventricular systolic pressure (RVSP) ≥ 20 mmHg with exercise, subsequently developed pulmonary hypertension (PH) compared with those who had persistently negative EE. The majority of patients with a baseline positive EE were found to have a persistently positive EE over time. However, interestingly, a proportion of those patients did not develop resting PAH. Similarly, 3 patients with baseline negative EE developed PAH shortly after initial testing, possibly representing a false-negative result. Because invasive hemodynamics with right heart catheterization (RHC) was not performed unless clinically indicated and was also performed up to 6 months following EE, it is difficult to ascertain the meaning of the present findings. Certainly, other SSc-specific features or biomarkers of increased risk in combination with positive EE need to be identified; however, lack of standardization in annual testing limits identification in this present study. In contrast, a negative EE may be helpful in identifying a group protected from developing PH in the future. This finding, if confirmed in larger studies, could lead to improved early detection strategies for patients with SSc at highest risk for development of PAH, and potentially other at-risk populations with connective tissue disease. The current study is an extension of an original 2008 manuscript, also by Steen, et al , in which SSc patients at risk for PAH underwent EE to determine whether … Address correspondence to Dr. M. Mukherjee, Johns Hopkins University Division of Cardiology, 301 Mason Lord Drive, Suite 2400, Baltimore, Maryland 21224, USA. E-mail: mmukher2{at}jhmi.edu

Myocardial infarctions may cause ventricular aneurysms. Ischemia-induced ventricular changes are more common in the left ventricle owing to the larger vascular supply, greater volume of myocardium, and increased intra-ventricular pressure. Ischemia-induced right ventricular free wall abnormalities are rare owing to the lower ventricular pressure. The authors describe the echocardiographic progression of a right ventricular ischemic aneurysm resulting from an ST-elevated myocardial infarction in a 71- year-old man. In this E-Challenge, the authors will review the echocardiographic findings and pathophysiology of ischemic aneurysms.

Background Turner syndrome (TS) is a X-chromosomal disease affecting one in 2500-3000 female newborns. TS individuals are at high cardiovascular risk and more likely to be overweight or obese. The aim of this study was to assess left ventricular performance in TS patients through three-dimensional speckle tracking echocardiography (3DSTE) and non-invasive left ventricular pressure-volume loop (PVL) analysis. Moreover, this study focused on the impact of excess weight on the left ventricular efficiency in TS patients. Methods Thirty-six TS patients and 19 healthy age-matched controls were included in this study. 3DSTE and non-invasive left ventricular PVL analysis were performed and left ventricular efficiency parameters were calculated. Results TS patients had significantly lower values than controls in longitudinal strain (- 16.67 ± 3.23% vs. - 18.47 ± 1.87%; p = 0.029), but significantly higher values for arterial elastance (BSA) (3.31, 1.87-5.88 mmHg/mL vs. 2.99, 2.31-4.61 mmHg/mL; p = 0.011) and cardiac work (BSA) (292,070 ± 71,348 mmHg*mL*HR vs. 248,595 ± 70,510 mmHg*mL*HR; p = 0.036). Compared with normal weight patients, overweight and obese TS subjects demonstrated worse left ventricular efficiency (175.08 ± 17.73 mmHg vs. 157.24 ± 26.75 mmHg; p = 0.037). Even after excluding TS patients with cardiovascular morbidity, arterial elastance (BSA) was compared to healthy peers, significantly increased in TS patients. Conclusions 3DSTE and non-invasive left ventricular PVL analysis might be useful tools to detect early cardiac changes in TS. Arterial elastance seems to be significantly increased in TS patients, independent of cardiovascular morbidity. Compared with normal weight TS patients, overweight/obese TS patients displayed lower left ventricular efficiency.

Congestion is a major determinant of clinical outcomes in heart failure (HF). We compared the acute hemodynamic effects of occlusion of the superior (SVC) versus the inferior vena cava (IVC) and tested a novel SVC occlusion system in swine models of HF. IVC occlusion acutely reduced left ventricular (LV) systolic and diastolic pressures, LV volumes, cardiac output (CO), and mean arterial pressure (MAP). SVC occlusion reduced LV diastolic pressure and volumes without affecting CO or MAP. The preCARDIA system is a balloon occlusion catheter and pump console which enables controlled delivery and removal of fluid into the occlusion balloon. At 6, 12, and 18 h, SVC therapy with the system provided a sustained reduction in cardiac filling pressures with stable CO and MAP. Intermittent SVC occlusion is a novel approach to reduce biventricular filling pressures in HF. The VENUS-HF trial will test the safety and feasibility of SVC therapy in HF.

BACKGROUND Left ventricular (LV) diastolic dysfunction is a prominent feature of hypertrophic cardiomyopathy (HCM). Prediction of LV filling pressure using the ratio between early diastolic transmitral flow and mitral annular velocity (E/e') had proved a good accuracy. AIM OF THIS STUDY We investigated the value of E/e' to predict cardiovascular (CV) mortality in patients with HCM. METHODS A total of 243 patients with HCM had E/e' measured in combination with clinical evaluation, conventional echocardiographic measurements, cardiopulmonary exercise evaluation, and Holter monitoring. RESULTS During a mean follow-up of (3.2 ± 1.2 years), 17 (7%) patients died. Non survivors had significantly higher SBP, DBP, left ventricular outflow tract obstruction (LVOTO) gradient, mitral E, and E/e', but lower e' of mitral annulus and more prevalent restrictive filling pattern. E/e' was directly correlated with age (r = .24, P

Aims The temporal sequence of events underlying functional right ventricular (RV) recovery after improvement of pulmonary hypertension-associated pressure overload is unknown. We sought to establish a novel mouse model of gradual RV recovery from pressure overload and use it to delineate RV reverse-remodelling events. Methods and results Surgical pulmonary artery banding (PAB) around a 26-G needle induced RV dysfunction with increased RV pressures, reduced exercise capacity and caused liver congestion, hypertrophic, fibrotic, and vascular myocardial remodelling within 5 weeks of chronic RV pressure overload in mice. Gradual reduction of the afterload burden through PA band absorption (de-PAB)—after RV dysfunction and structural remodelling were established—initiated recovery of RV function (cardiac output and exercise capacity) along with rapid normalization in RV hypertrophy (RV/left ventricular + S and cardiomyocyte area) and RV pressures (right ventricular systolic pressure). RV fibrotic (collagen, elastic fibres, and vimentin+ fibroblasts) and vascular (capillary density) remodelling were equally reversible; however, reversal occurred at a later timepoint after de-PAB, when RV function was already completely restored. Microarray gene expression (ClariomS, Thermo Fisher Scientific, Waltham, MA, USA) along with gene ontology analyses in RV tissues revealed growth factors, immune modulators, and apoptosis mediators as major cellular components underlying functional RV recovery. Conclusion We established a novel gradual de-PAB mouse model and used it to demonstrate that established pulmonary hypertension-associated RV dysfunction is fully reversible. Mechanistically, we link functional RV improvement to hypertrophic normalization that precedes fibrotic and vascular reverse-remodelling events.

Objective.To evaluate whether a positive exercise echocardiogram (EE) predicts future development of pulmonary arterial hypertension (PAH) in a high-risk cohort of patients with systemic sclerosis (SSc).Methods.Patients with SSc with features associated with an increased risk for PAH were recruited into a prospective, observational cohort. All patients underwent clinical assessment and EE. A positive EE was defined as an increase of ≥ 20 mmHg in the right ventricular systolic pressure with exercise. All patients with positive EE underwent right heart catheterization (RHC).Results.The study included 85 patients. In the positive EE cohort, 10 of 43 patients (23%) developed resting pulmonary hypertension (PH) on RHC over a mean 4-year followup period [4 with PAH, 5 with pulmonary venous hypertension (PVH), and 1 with PH associated with interstitial lung disease]. In the persistently negative EE cohort, only 3 of 42 patients (7%) developed resting PH (1 PAH, 2 PVH; p = 0.04). Of the remaining 33 patients in the positive EE group who did not develop resting PH, 22 (67%) had a persistently positive EE over an average 5-year followup period.Conclusion.In this high-risk cohort of patients with SSc, a positive EE may predict the future development of resting PH. In addition, a majority of patients may have a persistently positive EE for years without progression to resting PH. Finally, a consistently negative EE may identify patients at low risk for future PH.

Assessment of left ventricular diastolic function by transthoracic Doppler echocardiography is based on a multiparametric approach which includes the spectral tissue Doppler-derived E/e'. Recently, a new Doppler index, E/(e'xs'), which combines E/e' with a spectral tissue Doppler-derived marker of systolic function, s', has been proposed in noninvasive assessment of left ventricular myocardial dysfunction. Current literature provides evidence that E/(e'xs') has good correlation with NT proBNP levels and invasive left ventricular end-diastolic pressure, both used as markers of left ventricular myocardial dysfunction, irrespective of left ventricular ejection fraction and wall motion abnormalities. More specifically, E/(e'xs') has good diagnostic accuracy in patients with intermediate values for E/e' (8 to 15). Average E/(e'xs')>1.6 is reported to predict invasive left ventricular end-diastolic pressure>15mmHg with a sensitivity of 86% and a specificity of 85%. Current literature provides evidence that E/(e'xs') could offer better prognostic information than E/e' in patients with systolic heart failure and heart failure with normal ejection fraction, as well as in patients with asymptomatic heart disease. A few clinical studies also suggest that E/(e'xs') could predict recurrence of atrial fibrillation after cardioversion and left ventricular remodeling after acute myocardial infarction. Further experimental and clinical investigation is critically needed to determine the role of this under-recognized tissue Doppler index in noninvasive assessment of cardiovascular diseases, in particular heart failure with normal ejection fraction.

Background Glucagon-like peptide-1 (GLP-1) reduces cardiovascular events in diabetic patients; however, its counter-protective effects have also been suggested in patients with heart failure and the clear explanation for its mechanisms have not yet been offered. Methods The effects of GLP-1 analog on cardiac function and energy metabolism, especially glycemic and lipid metabolisms were elucidated using non-diabetic J2N-k hamsters which showed spontaneous dilated cardiomyopathy. J2N-k hamsters were treated with PBS (HF group), low-dose (HF-L group) or high-dose liraglutide (HF-H group). Results In failing heart, GLP-1 analog exerted further deteriorated cardiac function (e.g. positive and negative dP/dt; p = 0.01 and p = 0.002, respectively) with overt fibrosis and cardiac enlargement (heart/body weight, 5.7 ± 0.2 in HF group versus 7.6 ± 0.2 in HF-H group; p = 0.02). The protein expression of cardiac muscles indicated the energy starvation status. Indirect calorimetry showed that failing hearts consumed higher energy and carbohydrate than normal hearts; moreover, this tendency was augmented by GLP-1 analog administration. Upon 10% glucose solution loading with GLP-1 analog administration (HF-H-G group) as complementary experiments, the cardiac function and fibrosis significantly ameliorated, whereas carbohydrate utilization augmented further and lipid utilization reduced more. The prognosis of HF-H-G group also significantly improved (p = 0.025). Conclusions Glucagon-like peptide-1 analog caused the relative but desperate shortage of glycemic energy source for the failing cardiac muscles and it may restrict ATP synthesis, resulting in cardiac function deterioration. Therefore, appropriate energy supply and amount of carbohydrate intake should be carefully considered when administrating incretin-related drugs to patients with heart failure.

Background Sepsis leads to severe inflammatory and cardiac dysfunction. This study aimed to explore the clinical value of miR-495 in sepsis, as well as its role in sepsis-induced inflammation and cardiac dysfunction. Methods 105 sepsis patients were recruited; receiver operating characteristic (ROC) curve was plotted to assess the diagnostic value of miR-495 in sepsis. A model of sepsis in rats was created via performing cecal ligation and puncture (CLP). After modeling, the cardiac function, including left ventricular systolic pressure (LVSP), left ventricular end diastolic pressure (LVEDP) and maximum rate of rise/fall of left ventricle pressure (± dp/dtmax), and serum cardiac troponin I (CTn-I), creative kinase isoenzyme MB (CK-MB) were detected. The blood cytokines levels including TNF-α, IL-6, IL-1β were also measured. Quantitative real-time PCR (qRT-PCR) was used for the measurement of the expression level of miR-495. Results MiR-495 was significantly downregulated in sepsis patients, especially patients who suffered from septic shock (SS). MiR-495 expression was negatively associated with Scr, WBC, CRP, PCT, APACHE II score and SOFA score. MiR-495 could distinguish patients with SS from non-SS patients. MiR-495 and SOFA score were better indictors for the occurrence of cardiac dysfunction in sepsis patients. In CLP-induced sepsis model. CLP rats experienced deterioration of LVSP, LVEDP, ± dp/dtmax, and had a rise in serum CTn-I, CK-MB, TNF-α, IL-6 and IL-1β, which were improved by miR-495 agomir injection. Conclusions MiR-495 might be a potential diagnostic biomarker for sepsis patients, and overexpression of miR-495 alleviated sepsis-induced inflammation and cardiac dysfunction.

Patient: Male, 53 Final Diagnosis: Right ventricular dysfunction secondary to obesity hypoventilation syndrome Symptoms: Shortness of breath Medication: — Clinical Procedure: Echocardiogram (TTE) Specialty: Cardiology Objective: Challenging differential diagnosis Background: Obesity hypoventilation syndrome (OHS) is characterized by a body mass index (BMI) ≥30 kg/m2, daytime hypercapnia, an arterial carbon dioxide tension ≥45 mmHg, and obstructive sleep apnea (OSA). OHS can lead to pulmonary hypertension. It has not been clearly demonstrated that OHS with pulmonary hypertension can lead to right ventricular dysfunction and right heart failure. A case is presented of right ventricular dysfunction and right ventricular failure secondary to OHS. Case Report: A 53-year-old man, who was morbidly obese with a BMI of 75 kg/m2, presented with shortness of breath (SOB) and hypercapnia. He had never smoked but had a history of severe OSA and hypertension. On examination, the patient was obese with normal lung auscultation and mild pitting edema of the lower extremities. A spiral computed tomography (CT) angiogram showed no evidence of pulmonary embolism or interstitial lung disease. Pulmonary function testing showed no obstructive airway disease and a normal diffusion capacity. Two-dimensional transthoracic echocardiogram (TTE) showed normal left ventricular function and a dilated right ventricle (RV) with a flattened septal wall, moderate tricuspid regurgitation, and an estimated right ventricular systolic pressure of 55–60 mmHg. The patient was discharged on continuous positive airway pressure (CPAP) and oxygen at night, and as needed during the day. Conclusions: This report has shown that OHS without underlying causes of alveolar hypoventilation can result in isolated right ventricular dysfunction and right ventricular failure.

Objectives To evaluate possible treatment-related hemodynamic changes, we administered ranolazine or mexiletine to swine with heart failure (HF) and to controls. Background Ranolazine and mexiletine potently inhibit depolarizing late Na+ current (INa,late) and Na+ entry into cardiomyocytes. Blocking Na+ entry may increase forward-mode Na/Ca exchange and reduce cellular Ca+2 load, further compromising systolic contraction during HF. Methods and Results Anesthetized tachypaced HF swine received ranolazine (n = 9) or mexiletine (n = 7) as boluses, then as infusions; the same experiments were performed in 10 nonpaced controls. The swine with HF had characteristic elevated left ventricular end-diastolic pressure (LVEDP) and reduced maximal left ventricular pressure rise (+dP/dtmax) and left ventricular peak systolic pressure (LVSP). No significant change occurred after ranolazine dosing for any parameter: LVEDP, +dP/dtmax, LVSP, heart rate, maximal LV pressure fall rate (–dP/dtmax), or time constant for isovolumic relaxation. Similar results seen in additional swine with HF: 7 were given mexiletine, and 7 others were given ranolazine after a 27% rate decrement to maximize INa,late. Patch-clamped HF cardiomyocytes confirmed drug-induced INa,late blockade. Conclusions Ranolazine or mexiletine blocking INa,late neither worsened nor improved hemodynamics during advanced HF. Although results must be clinically confirmed, they suggest inhibition of INa,late by ranolazine or mexiletine may not exacerbate HF in patients.

Background: Targeted neonatal echocardiography (TNE) is proposed to describe the use of targeted neonatal echocardiography to assess systemic and pulmonary blood flow, myocardial function, intracardiac and extra cardiac shunts, organ blood flow and tissue perfusion. It gives non-invasive information on the underlying cardiovascular pathophysiology causing hemodynamic instability and the response to treatment in an individual patient over time. Objective: Our main objective in this study is to delineate the impact of echocardiography on the management of unstable neonates at neonatal ICU at Sohag University Hospital.Methods: A prospective hospital-based study included 191 neonates. TNE was done for all included infants as indicated by the clinical team. TNE used to assess PDA regarding diagnosis of patency and hemodynamic significance.. Right ventricular systolic pressure and Pulmonary artery pressure was assessed for diagnosis, management and follow up pf pulmonary hypertension. The main outcome was measured by the impact of TNE on the management plane of the included infants and their short term outcome. Results: there were 60 (31.41%) preterm newborns have PDA, 45 (75%) of them were hemodynamically significant, of them 28 were closed by medical treatment, 15 needed surgical ligation and 2 infants were died. There were 28 (14.65%) newborns had pulmonary hypertension, 27 cases were improved using medical treatment and one case died.

Aortic valve stenosis is associated with an elevated left ventricular pressure and transaortic pressure drop. Clinicians routinely use Doppler ultrasound to quantify aortic valve stenosis severity by estimating this pressure drop from blood velocity. However, this method approximates the peak pressure drop, and is unable to quantify the partial pressure recovery distal to the valve. As pressure drops are flow dependent, it remains difficult to assess the true significance of a stenosis for low-flow low-gradient patients. Recent advances in segmentation techniques enable patient-specific Computational Fluid Dynamics (CFD) simulations of flow through the aortic valve. In this work a simulation framework is presented and used to analyze data of 18 patients. The ventricle and valve are reconstructed from 4D Computed Tomography imaging data. Ventricular motion is extracted from the medical images and used to model ventricular contraction and corresponding blood flow through the valve. Simplifications of the framework are assessed by introducing two simplified CFD models: a truncated time-dependent and a steady-state model. Model simplifications are justified for cases where the simulated pressure drop is above 10 mmHg. Furthermore, we propose a valve resistance index to quantify stenosis severity from simulation results. This index is compared to established metrics for clinical decision making, i.e. blood velocity and valve area. It is found that velocity measurements alone do not adequately reflect stenosis severity. This work demonstrates that combining 4D imaging data and CFD has the potential to provide a physiologically relevant diagnostic metric to quantify aortic valve stenosis severity.

The aim of this study was to evaluate the influence of acute kidney injury caused by high doses of folic acid on cardiac function and markers of oxidative stress in serum and isolated rat heart. Isolated hearts of Wistar albino rats (divided into two groups: control and folic acid group) were perfused according to Langendorff technique at basal coronary perfusion pressure CPP of 70 cm H2O. After a stabilization period, CPP was lowered to 60 cm H2O and then gradually increased to 80, 100, 120 and finally decreased to 40 cm H2O in order to establish coronary autoregulation. For each perfusion pressure value, the left ventricular function parameters were determined. Samples of coronary venous effluent were collected for determination of coronary flow and biomarkers of oxidative stress. The blood samples were collected in order to examine the values of serum urea, creatinine, Na, K, and parameters of oxidative stress and antioxidant defense system. Heart and kidney tissue samples were collected for histopathological examination. Folic acid group showed reduction of systolic and diastolic left ventricular pressure and increase of coronary flow and minimum left ventricular pressure development rate. In coronary flow, folic acid group showed increased levels of TBARS and reduction of H2O2 and NO2−. Serum ROS concentrations were lower in rats treated with folic acid, particularly levels of TBARS and NO2− in which values were significantly lower. The parameters of systemic antioxidative stress were at significantly high levels especially SOD and GSH. This study is the experimental confirmation of cardio-renal syndrome type 3, which represents the acute kidney injury that causes a damage of a heart function. The data suggest that negative effects of acute kidney injury on myocardium do not necessarily involve oxidative stress, which may lead to future investigations which will be based on inflammation as a one of the important factors in the organ crosstalk.

Background: Pacing the right heart has been shown to induce reversible conduction delay and subse­quent asymmetric remodeling of the left ventricle (LV) in dogs and pigs. Both species have disadvantages in animal experiments. Therefore the aim of this study was to develop a more feasible and easy-to-use animal model in sheep. Methods: Dual-chamber (DDD) pacemakers with epicardial leads on the right atrium and right ven­tricular free wall were implanted in 13 sheep. All animals underwent 8 weeks of chronic rapid pacing at 180 bpm. Reported observations were made at 110 bpm. Results: DDD pacing acutely induced a left bundle branch block (LBBB) — like pattern with almost doubling in QRS width and the appearance of a septal flash, indicating mechanical dyssynchrony. Atrial pacing (AAI) resulted in normal ventricular conduction and function. During 8 weeks of rapid DDD pacing, animals developed LV remodeling (confirmed with histology) with septal wall thinning (–30%, p < 0.05), lateral wall thickening (+22%, p < 0.05), LV volume increase (+32%, p < 0.05), decrease of LV ejection fraction (–31%, p < 0.05), and functional mitral regurgitation. After 8 weeks, segmental pressure-strain-loops, representing regional myocardial work, were recorded. Switching from AAI to DDD pacing decreased immediately work in the septum and increased it in the lateral wall (–69 and +41%, respectively, p < 0.05). Global LV stroke work and dP/dtmax decreased (–27% and -25%, respectively, p < 0.05). Conclusions: This study presents the development a new sheep model with an asymmetrically remod­eled LV. Simple pacemaker programing allows direct modulation of regional myocardial function and work. This animal model provides a new and valuable alternative for canine or porcine models and has the potential to become instrumental for investigating regional function and loading conditions on regional LV remodeling.

Left ventricle assist devices (VADs) aid the heart pumping blood into the systemic circulation and grant the required cardiac output (CO) when the heart itself cannot provide it. However, it is unclear how effective these devices are at restoring not only physiological CO values but also normal intraventricular hemodynamics. In this work, the modified hemodynamics due to a VAD implantation is studied in vitro using an elastic ventricle made of silicone, which is incorporated into a pulse-duplicator setup prescribing a realistic pulsatile flow. Thereafter, a continuous axial pump is connected at the ventricle apex to mimic a VAD and its effect on the ventricular hemodynamics is investigated as a function of the pump flow suction. Using particle image velocimetry (PIV), we observe that the continuous pump flow effectively provides unloading on the ventricle and yields an increased CO. Conversely, the continuous blood suction from the ventricle apex deeply alters the hemodynamics and, in addition, the VAD obstruction in the ventricle behaves as a bluff body that affects the vorticity distribution in the LV thus creating a stagnant region at the ventricle apex. This phenomenon is rationalized by measuring in a modified set-up the benefits on the hemodynamics of a flush-mounted device. Additionally, the suction operated by the VAD reduces the ventricular pressure and yields an increase in the swirling motion around the ventricle axis, in a similar fashion as the bath-tub vortex effect, thus further modifying the intraventricular hemodynamics with respect to healthy conditions.

Objectives Prior studies have shown that left ventricular diastolic dysfunction (DD) is associated with increased mortality after surgical aortic valve replacement but studies on transcatheter aortic valve replacement (TAVR) are limited and have not taken into account mitral annular calcification (MAC), which limits the use of mitral valve annular tissue Doppler imaging. We performed a single-center retrospective analysis to better evaluate the role of baseline DD on outcomes after TAVR. Methods After excluding patients with atrial fibrillation, mitral valve prostheses and significant mitral stenosis, 359 consecutive TAVR patients were included in the study. Moderate-to-severe MAC was present in 58% of the patients. We classified patients into severe versus nonsevere DD based on the evaluation of elevated left ventricular filling pressure. The outcome measure was all-cause mortality or heart failure hospitalization. Results Over a mean follow-up time of 13 months, severe DD was associated with an increased risk for the outcome measure (HR 2.02 [1.23-3.30], p = .005). However, this association was lost in a propensity-matched cohort. In multivariate analysis, STS score was the only independent predictor of all cause mortality of heart failure hospitalization (HR 1.1 [1.05-1.15], p Conclusions We evaluated the role of baseline DD on outcomes after TAVR by taking into account the presence of MAC. Severe DD was associated with increased all-cause mortality or heart failure hospitalization but not independently of other structural parameters and known predictors of the outcome measure.

The inter-relationships between minimal and maximal left atrial volume index (LAVI), left ventricular filling pressures and survival have not been well studied. This study aimed to compare LAVImin with LAVImax with respect to (1) relative prognostic value, and (2) correlation with left ventricular end-diastolic pressures (LVEDP), in patients with myocardial infarction (MI). A retrospective study involving consecutive patients with a first-ever MI (n = 419) was undertaken. LAVIs were determined using Simpson's biplane method from 2D echocardiography performed the day after admission. LAVmin ≥ 18 mls/m2 and LAVImax ≥ 34 mls/m2 were considered enlarged. The primary end point was composite major adverse cardiovascular events (MACE) (death/MI/heart failure). Correlation between LVEDP and LAVI was assessed in 120 patients who underwent echocardiography and cardiac catheterization either simultaneously (n = 30) or same-day (n = 90). At a median follow-up of 24 months, there were 61 MACE events. On Cox proportional hazards multivariate analysis incorporating significant clinical predictors and LVEF, whereas both LAVImin ≥ 18 mls/m2 (hazard ratio 3.15 [95% confidence interval 1.70 to 5.54], p

INTRODUCTION AND OBJECTIVE Pulmonary hypertension (PH) complicating idiopathic pulmonary fibrosis (IPF) is challenging to diagnose given inaccuracy of transthoracic echocardiogram (TTE) measurements. However, it has significant prognostic implications and is therefore important to accurately identify. METHODS We conducted a cross-sectional study of patients with IPF who underwent RHC as part of their evaluation. A variety of commonly available noninvasive variables were evaluated for their ability to predict pulmonary arterial pressure in a linear regression model, including the traditionally used right ventricular systolic pressure (RVSP) estimated from TTE. RESULTS There were 105 eligible patients identified from January 2006 to July 2016. The average age was 62.7 ± 7.7 years, 35 had RHC proven PH and 43% ultimately underwent lung transplantation. A linear model including three terms: RVSP (ANOVA P

2016 guidelines for the echographic evaluation of left ventricular filling pressure (LVFP) proposed a single algorithm with limited number of criteria (E/A ratio, tricuspid regurgitation velocity, left atrial volume index and average E/e′) mainly related to left atrial pressure. Pulmonary venous flow analysis, evaluating more specifically left ventricular end diastolic pressure (LVEDP) has been withdrawn. We aim to evaluate the proportion of patients diagnosed with normal LVFP according to 2016 recommendations, despite an abnormal pulmonary venous flow profile suggesting high LVEDP. We prospectively studied patients with stable ischemic cardiomyopathy and aortic stenosis, before cardiac surgery. Extensive echocardiography was performed including pulmonary and mitral A wave durations. We included 76 patients (mean age 72 ± 10 years, 78% were men), 37 (49%) with aortic stenosis and 22 (29%) with ischemic cardiomyopathy. Mean left ventricular ejection fraction was 67 ± 11%. Applying recommendations, 58 patients had normal LVFP and 15 patients had high LVFP. Among the 58 patients with normal LVFP, 26 patients had Apd–Amd duration > 30 ms highly suggestive of high LVEDP. These patients had higher LV mass (112 ± 30 g/m2 vs. 86 ± 20 g/m2, p = 0.004) and shorter A wave duration (120 ± 13.6 ms vs. 132 ± 16.5 ms, p = 0.006) as compared to the remaining 15 patients with concordant evaluation (normal LVFP and normal Apd–Amd). In the present study, we found that 26/58 patients with low LVFP according to the 2016 recommendations had Apd–Amd suggestive of high LVEDP. Pulmonary venous flow should be added to the algorithm, particularly in patients with unexplained symptom, high LV mass or truncated mitral A wave.

BACKGROUND Primary graft dysfunction (PGD) represents ischemia‒reperfusion injury in the lung allograft, and elevated left ventricular end-diastolic pressure (LVEDP) may contribute to capillary leak. We tested whether pre-transplant LVEDP or pulmonary capillary wedge pressure (mPCWP) are related to PGD risk. We hypothesized that elevated LVEDP and mPCWP would increase PGD risk. METHODS We reviewed adult double lung transplant recipients at the University of Alberta Hospital from 2004 to 2016 with pre-transplant LVEDP measurements. The primary outcome was Grade 3 PGD at 48 to 72 hours post-transplant. We used regression analysis to assess the association between LVEDP and mPCWP with Grade 3 PGD risk, as well as agreement between these measurements. RESULTS Three hundred thirty double lung transplant recipients were included in the study, and 63 (19%) developed Grade 3 PGD at 48 or 72 hours. Mean LVEDP was 16 ± 7 mm Hg in the Grade 3 PGD group and 12 ± 5 mm Hg in the non-PGD group ( p 15 mm Hg was associated with an adjusted odds ratio (OR) of 3.83 (95% confidence interval [CI] 1.90 to 7.73, p 15 mm Hg showed similar findings (adjusted OR 4.25 [1.83 to 9.86], p = 0.0008). Correlation and agreement between LVEDP and mPCWP were fair. CONCLUSIONS Elevated pre-transplant LVEDP increases the risk of severe PGD after lung transplant, as does elevated mPCWP. These measurements appear to be complementary as markers of prospective PGD risk.

Cardiovascular diseases may originate from suboptimal intrauterine environments. We aimed to examine the effects of prenatal androgen exposure (PAE) on heart basal hemodynamic parameters and tolerance to ischemia/reperfusion (I/R) injury, in PAE adult females and males.Pregnant Wistar rats in the experimental group (n = 8) received 5 mg of testosterone (s.c. injection) on the 20th day of pregnancy, while controls received solvent. The hearts of adult female and male offspring were isolated and perfused in a Langendorff apparatus, values of left ventricular systolic pressure(LVSP), left ventricular developed pressure(LVDP), rate pressure product(RPP) and peak rates of positive and negative changes in left ventricular pressure(±dp/dt) were recorded using a power lab system.At baseline, PAE adult males demonstrated significant higher values of LVSP, LVDP, RPP and ± dp/dt, compared to controls and PAE adult females (p 0.05), while PAE adult females showed no significant differences compared to controls. In PAE adult males, LVSP, LVDP, RPP and ± dp/dt had significant decreasing trends per phases after I/R, compared to their controls and PAE females, while these decreasing trends were not statistically significant in PAE adult female rats vs. their controls.The impact of prenatal androgen exposure on adulthood cardiac function and tolerance to I/R is gender dependent, which may be partly explained by different cardiac effects of hyperandrogenism in males versus females. After prenatal androgen exposure, the baseline hemodynamic parameters of the hearts of adult males are increased; although they had less tolerance to I/R, findings however not observed in females.

Given the therapeutic efficacy of fasudil hydrochloride (F) and dichloroacetate (DCA) on pulmonary arterial hypertension (PAH), a new salt fasudil dichloroacetate (FDCA) was designed, synthesized and biologically evaluated. FDCA exhibited comparable ROCK II inhibitory activity relative to fasudil hydrochloride, and suppressed the expression of TNF-α and IL-6 in both PDGF-BB and hypoxia-treated pulmonary arterial smooth muscle cells (PASMCs) and endothelial cells (PAECs). Significantly, FDCA lowered mean pulmonary artery pressure (mPAP) and right ventricular systolic pressure (RVSP), and decreased right ventricular hypertrophy (RVH) in monocrotaline (MCT)-induced PAH rats. Meanwhile, FDCA remarkably decreased pulmonary artery medial thickness (PAMT) and hyperplasia, restoring the elasticity of elastic fiber, reduced cardiac hypertrophy, and attenuated fibrosis of heart and lung. Collectively, FDCA exhibited triple activities of pulmonary vasodilation, vascular remodeling inhibition and RVH inhibition, suggesting that it may be a promising agent for PAH intervention.

Introduction: Right ventricular (RV) failure due to pressure load is an important determinant of clinical outcome in pulmonary hypertension, congenital heart disease and left ventricular failure. The last decades it has become clear that metabolic dysregulation is associated with the development of RV-failure. However, underlying mechanisms remain to be unraveled. Recently, disruption of intracardiac lipid content has been suggested as potential inducer of RV failure. In the present study, we used a rat model of RV-dysfunction and aimed to obtain insight in temporal changes in RV-function, -remodelling and -metabolism and relate this to RV lipid content.Methods and results: Male Wistar WU rats were subjected to pulmonary artery banding (n=25) or sham surgery (n=14) and cellular, hemodynamic and metabolic assessments took place after 2, 5 and 12 weeks. In this model RV dysfunction and remodelling occurred, including early upregulation of oxidative stress markers. After 12 weeks of pressure load, lipidomics revealed significant decreases of myocardial diglycerides and cardiolipins, driven by (poly-) unsaturated forms. The decrease of cardiolipins was driven by its most abundant form, tetralinoleoylcardiolipin. Mitochondrial capacity for fatty acid oxidation preserved, while the capacity for glucose oxidation increased.Conclusion: RV dysfunction due to pressure load, is associatedwith decreased intracardiac unsaturated lipids, especially tetralinoleoylcardiolipin. This was accompanied with preserved mitochondrial capacity regarding fatty acids oxidation, with increased capacity for glucose oxidation, and early activation of oxidative stress. We suggest that early interventions should be directed towards preservation of lipid availability as possible mean in order to prevent RV failure. (c) 2019 Published by Elsevier B.V.

Adrenaline (epinephrine) is one of the prime messengers of the fight-or-flight response, favoring the activation of β-adrenergic receptors. Although general vasoconstriction to nonessential tissues is imperative, the vasodilatory effect of β-adrenergic receptor activation contends with this. We aimed to determine the dose-dependent effects of adrenaline on hemodynamics and to test whether adrenaline could lower blood pressure (BP) through a β2-adrenergic pathway. Nineteen Danish landrace pigs were used to pharmacologically probe the hemodynamic effect of adrenaline. Pigs were anesthetized, intubated, and electrocardiogram, systolic BP (SBP), diastolic BP (DBP), and left ventricular pressure (LVP) were monitored continuously. First, we tested the dose-dependent effects of adrenaline (0.01-10 µg/kg). Second, we determined the response to adrenaline (0.3 µg/kg) after atropine, prazosin, and propranolol pretreatment. Finally, we tested the hemodynamic effect of salbutamol in a subset of pigs. All doses of adrenaline increased heart rate, while BP showed a biphasic response: At low doses, adrenaline decreased SBP from 118 ± 3 to 106 ± 4 mm Hg (n = 15; P < 0.05) and DBP from 86 ± 3 to 71 ± 3 (n = 15; P < 0.05), while at high doses, SBP and DBP increased. LVP showed a similar pattern, with a tendency of decreased pressure at low doses, and an increased pressure at high doses (P < 0.05). Pretreatment with autonomic blockers revealed that the increase in BP was due to α-adrenergic activity, while the decrease was due to β-adrenergic activity. In confirmation, β-adrenergic activation through salbutamol showed a similar decrease in SBP, DBP, and LVP. We conclude that adrenaline dose-dependently increases heart rate, while producing a biphasic response in BP with a decrease at low doses and an increase at high doses in an anesthetized, large-animal model.

BACKGROUND A weak correlation has been reported between left ventricular filling pressures and the traditional echocardiographic tools for the evaluation of diastolic function in patients with coronary artery disease (CAD) and preserved left ventricular ejection fraction (LVEF). On the other hand, studies that compared invasive measurements with speckle tracking echocardiography have shown promising results, but they were not exclusively targeted on this specific population. METHODS AND RESULTS Immediately before the left heart catheterization, a comprehensive two-dimensional Doppler echocardiography and speckle tracking analysis was prospectively performed in outpatients referred for coronary angiography. Left ventricular end-diastolic pressure (LVEDP) was measured before any contrast exposure. Eighty-one patients with coronary artery disease were studied, and the group with high LVEDP (n = 40) showed increased left atrial volume index (22 ± 6 mL/m2 vs 26 ± 8.26 mL/m2 , P = 0.04), E-wave velocity (65 ± 15 cm/s vs 78 ± 20 cm/s, P = 0.02), E/e` (average) ratio (8.14 ± 2.0 vs 11.54 ± 2.7, P = 0.03), and E/global circumferential strain rate E peak ratio (E/GCSRE ) (39 cm vs 46 cm, P

This meta-analysis assesses left atrial (LA) cavity and myocardial function measurements that predict pulmonary capillary wedge pressure (PCWP).PubMed-MEDLINE, EMBASE, Scopus, Google Scholar and the Cochrane Central Registry were searched up to December 2018 for studies on the relationship of LA diameter, LA indexed volume (LAVI max, LAVI min), peak atrial longitudinal (PALS), peak atrial contraction (PACS) strain and total emptying fraction (LAEF) with PCWP. Eighteen studies with 1343 patients were included. Summary sensitivity and specificity (with 95% CI) for evaluation of diagnostic accuracy and the best cut-off values for different LA indices in predicting raised PCWP were estimated using summary receiver operating characteristic analysis.The pooled analysis showed association between PCWP and LA diameter: Cohen's d = 0·87, LAVI max: d = 0·92 and LAVI min: d = 1·0 (P0·001 for all). A stronger correlation was found between PCWP and PALS: d = 1·26, and PACS: d = 1·62, total EF d = 1·22 (P0·0001 for all). PALS ≤19% had a summary sensitivity of 80% (65-90) and summary specificity of 77% (52-92), positive likelihood ratio (LR+) 3·74, negative likelihood ratio (LR-)0·25 and DOR 15·1 whereas LAVI ≥34 ml mCompromised LA myocardial function and increased size predict raised cavity pressure. These results should assist in optimum follow-up of patients with fluctuating LA pressure.

BACKGROUND Diastolic dysfunction (DD) is a characteristic of heart failure with preserved ejection fraction (HFpEF), which is thought to be caused by cardiac hypertrophy or fibrosis. Activin A is involved in the inflammatory response and myocardial fibrosis, but the relationship between the activin A level and DD remains unclear.Methods and Results:A total of 209 patients with stable angina were enrolled. Serum activin A levels were assessed, and echocardiography and cross-sectional analysis were performed. Among the subjects (65% male; mean age, 70±13 years), 84 (40%) subjects had DD. The subjects were divided into tertiles based on activin A levels. Patients in the high activin A group had enhanced left ventricular mass indexes, medial E/e' ratios, left atrial diameter, and right ventricular systolic pressure compared with those in the lower activin A groups (all P

Elevated left ventricular end diastolic pressure is a risk factor for ventricular arrhythmias in patients with tetralogy of Fallot. The objective of this retrospective study was to identify echocardiographic measures associated with left ventricular end diastolic pressure >12 mmHg in this population. Repaired tetralogy of Fallot patients age ≥13 years, who underwent a left heart catheterisation within 7 days of having an echocardiogram were evaluated. Univariate comparison was made in echocardiographic and clinical variables between patients with left ventricular end diastolic pressure >12 versus ≤12 mmHg. Ninety-four patients (54% male) with a median age of 24.6 years were included. Thirty-four (36%) had left ventricular end diastolic pressure >12 mmHg. Patients with left ventricular end diastolic pressure >12mmHg were older (median 32.9 versus 24.0 years, p = 0.02), more likely to have a history of an aortopulmonary shunt (62% versus 38%, p = 0.03), and have a diagnosis of hypertension (24% versus 7%, p = 0.03) compared to those with left ventricular end diastolic pressure ≤12 mmHg. There were no significant differences in mitral valve E/A ratio, annular e’ velocity, or E/e’ ratio between patients with left ventricular end diastolic pressure >12 versus ≤12 mmHg. Patients with left ventricular end diastolic pressure >12mmHg had larger left atrial area (mean 17.7 versus 14.0 cm2, p = 0.03) and larger left atrium anterior–posterior diameter (mean 36.0 versus 30.6 mm, p = 0.004). In conclusion, typical echocardiographic measures of left ventricular diastolic dysfunction may not be reliable in tetralogy of Fallot patients. Prospective studies with the use of novel echocardiographic measures are needed.

PURPOSE: With new repair techniques of the aortic root and valve emerging, a detailed understanding of the dynamics of the aortic annulus and valve is required for optimal results. The objective of this study was to characterize geometrical changes and force distribution of the native porcine aortic annulus throughout the cardiac cycle.METHODS: Measurements were performed in an acute 80 kg porcine model (n = 7) using sonomicrometry crystals in the aortic annulus for evaluation of geometry and dynamics, annular force transducer evaluating force distribution, and pressure measurements and echocardiography evaluating valve performance.RESULTS: Overall, segmental force distribution and geometrical changes differed between different segments of the aortic annulus. The highest force development was found at the left/right interleaflet triangle (2.87 ± 2.1 N) and the largest segmental expansion was observed at the right-coronary and left-coronary sinus. The aortic annulus changed configuration throughout the cardiac cycle and became more oval in systole.CONCLUSIONS: This study is the first to describe detailed segmental dynamics and force distribution of the native aortic annulus in a porcine model in vivo. The heterogenous behavior of the aortic annulus suggests that different segments demand different support for repair of the aortic root and valve.