Electrocardiographic abnormalities and NT-proBNP levels at long-term follow-up of patients with dyspnea after pulmonary embolism.

OBJECTIVES: Electrocardiogram (ECG) and measurement of plasma brain natriuretic peptides (BNP) are established markers of right ventricular dysfunction (RVD) in the setting of acute pulmonary embolism (PE) but their value at long-term follow-up is largely unknown. The purpose of this prospective study was to determine the prevalence of ECG abnormalities, describe levels of N-terminal proBNP (NT-proBNP), and establish their association with dyspnea at long-term follow-up after PE. DESIGN: All Swedish patients diagnosed with acute PE in 2005 (n = 5793) were identified through the Swedish National Patient Registry. Surviving patients in 2007 (n = 3510) were invited to participate. Of these, 2105 subjects responded to a questionnaire about dyspnea and comorbidities. Subjects with dyspnea or risk factors for development of chronic thromboembolic pulmonary hypertension were included in the study in a secondary step, which involved collection of blood samples and ECG registration. RESULTS: Altogether 49.3% had a completely normal ECG. The remaining participants had a variety of abnormalities, 7.2% had atrial fibrillation/flutter (AF). ECG with any sign of RVD was found in 7.2% of subjects. Right bundle branch block was the most common RVD sign with a prevalence of 6.4%. An abnormal ECG was associated with dyspnea. AF was associated with dyspnea, whereas ECG signs of RVD were not. 61.2% of subjects had NT-proBNP levels above clinical cut-off (>125 ng/L). The degree of dyspnea did not associate independently with NT-proBNP levels. CONCLUSIONS: We conclude that the value of ECG and NT-proBNP in long term follow-up after PE lies mostly in differential diagnostics.

Expression of ApoA5 and its function in the right ventricular failing and remodeling secondary to pulmonary hypertension.

Right heart failure and right ventricular (RV) remodeling were the main reason for mortality of pulmonary hypertension (PH) patients. Apolipoprotein AV (ApoA5) is a key regulator of plasma triglyceride and have multifunction in several target organs. We detected decreased ApoA5 in serum of patients with PH and both in serum and RV of monocrotaline-induced PH model. Exogenously, overexpression ApoA5 by adenovirus showed protective effects on RV failure and RV fibrosis secondary to PH. In addition, in vitro experiments showed ApoA5 attenuated the activation of fibroblast induced by transforming growth factor ß1 and synthesis and secretion of extracellular matrix by inhibiting focal adhesion kinase-c-Jun N-terminal kinase-Smad3 pathway. Finally, we suggest that ApoA5 may potentially be a pivotal target for RV failure and fibrosis secondary of PH.

Clinically inapparent right heart dysfunction is associated with reduced myofilament force development in coronary artery disease.

BACKGROUND: Right ventricular dysfunction after CABG is associated with poor peri- and postoperative outcomes. We aimed to identify clinical and experimental predictors for preoperative inapparent right ventricular dysfunction and therefore hypothesized that reduced myofilament force development as well as altered levels of biomarkers might predict inapparent right ventricular dysfunction. METHODS: From 08/2016 to 02/2018, 218 patients scheduled for CABG were divided into two groups (TAPSE ≥ 20 mm, n = 178; TAPSE < 20 mm, n = 40). Baseline serum samples for biomarkers (Galectin, TGFß1, N Acyl-SDMA, Arginine, ADMA and Pentraxin-3), clinical laboratory and transthoracic echocardiographic parameters were evaluated. To examine the myocardial apparatus of the right ventricle intraoperative right auricular tissue was harvested for stepwise skinned fiber force measurements. RESULTS: Patients with TAPSE < 20 mm had a higher incidence of DM (55 vs. 34%, p = 0.018), preoperative AFib (43 vs. 16%, p < 0.001), reduced GFR (67 ± 18 vs. 77 ± 24 ml/min/1.73 m2, p = 0.013), larger LA area (22 ± 6 vs. 20 ± 5 cm2, p = 0.005) and reduced LVEF (50 vs. 55%, p = 0.008). Furthermore, higher serum ADMA (0.70 ± 0.13 vs. 0.65 ± 0.15 µmol/l, p = 0.046) and higher serum Pentraxin-3 levels (3371 ± 1068 vs. 2681 ± 1353 pg/dl, p = 0.004) were observed in these patients. Skinned fiber force measurements showed significant lower values at almost every step of calcium concentration (pCa 4.52 to pCa 5.5, p < 0.01 and pCa 5.75-6.0, p < 0.05). Multivariable analysis revealed DM (OR 2.53, CI 1.12-5.73, Euro Score II (OR 1.34, CI 1.02-1.78), preoperative AF (OR 4.86, CI 2.06-11.47), GFR (OR 7.72, CI 1.87-31.96), albumin (OR 1.56, CI 0.52-2.60), Pentraxin-3 (OR 19.68, CI 14.13-25.24), depressed LVEF (OR 8.61, CI 6.37-10.86), lower force values: (pCa 5.4; OR 2.34, CI 0.40-4.29 and pCa 5.2; OR 2.00, CI 0.39-3.60) as predictors for clinical inapparent right heart dysfunction. CONCLUSIONS: These preliminary data showed that inapparent right heart dysfunction in CAD is already associated with reduced force development of the contractile apparatus.

A predictive tool for the assessment of right ventricular dysfunction in non-high-risk patients with acute pulmonary embolism.

BACKGROUND: Rapid and accurate identification of right ventricular (RV) dysfunction is essential for decreasing mortality associated with acute pulmonary embolism (PE), particularly for non-high-risk patients without hypotension on admission. This study aimed to develop a rapid and accurate tool for predicting the risk of RV dysfunction in non-high-risk patients with acute PE. METHODS: The medical records of non-high-risk patients with acute PE admitted to Shengjing Hospital of China Medical University between January 2011 and May 2020 were retrospectively analysed. The primary outcome of this study was RV dysfunction within 24 h after admission. The enrolled patients were randomized into training or validation sets as a ratio of 2:1. In the training set, a nomogram was developed, and the consistency was corroborated in the validation set. The areas under the receiver operating characteristic curves (AUCs) and 95% confidence intervals (CIs) were calculated. RESULTS: A total of 845 patients were enrolled, including 420 men and 425 women with an average age of 60.05 ± 15.43 years. Right ventricular dysfunction was identified in 240 patients (28.40%). The nomogram for RV dysfunction included N-terminal pro-brain natriuretic peptide, cardiac troponin I, and ventricular diameter ratios, which provided AUC values of 0.881 in the training dataset (95% confidence interval (CI): 0.868-0.898, p < 0.001) and 0.839 in the validation set (95% CI: 0.780-0.897, p < 0.001). The predictive tool was published as a web-based calculato ( https://gaoyzcmu.shinyapps.io/APERVD/ ). CONCLUSIONS: The combination of CT and laboratory parameters forms a predictive tool that may facilitate the identification of RV dysfunction in non-high-risk patients with acute PE.

Type IV Collagen 7s Reflects Central Venous Pressure and Right Ventricular End-Diastolic Pressure in Patients with Congenital Heart Disease After Biventricular Repair.

After congenital heart disease repair, right heart dysfunction facilitates venous stasis and elevated central venous pressure; however, methods to evaluate right heart dysfunction are limited. We aimed to evaluate right heart function using liver biomarkers. We investigated 62 patients more than 5 years after congenital heart surgery. The patients underwent cardiac catheterization in our hospital between January 2015 and December 2019. To evaluate liver status, type IV collagen 7s, procollagen type III peptide, and hyaluronic acid levels were measured. The mean age of the 62 patients was 14.0 ± 7.2 years. The mean central venous pressure was 6.8 ± 3.5 mmHg and mean right ventricular end-diastolic pressure was 7.9 ± 3.5 mmHg. The mean levels of serum type IV collagen 7s, procollagen type III peptide, and hyaluronic acid were 5.9 ± 1.6 ng/mL, 24.3 ± 15.5 ng/mL, and 18.5 ± 13.6 ng/mL, respectively. There was a good correlation between central venous pressure, right ventricular end-diastolic pressure and type IV collagen 7s (r = 0.67 and r = 0.64). There was no correlation between central venous pressure and the procollagen type III peptide (r = 0.003), and slight correlation between central venous pressure and hyaluronic acid (r = 0.31). There was no correlation between right ventricular end-diastolic pressure and the procollagen type III peptide (r = 0.003), and slight correlation between right ventricular end-diastolic pressure and hyaluronic acid (r = 0.31). We found that changes in the hemodynamics of the right heart system can be evaluated using liver fibrosis markers. Type IV collagen 7s reflects central venous pressure and right ventricular end-diastolic pressure in postoperative patients with congenital heart disease.

Inflammatory Biomarkers in the Short-Term Prognosis of Venous Thromboembolism: A Narrative Review.

The relationship between inflammation and venous thrombosis is not well understood. An inflammatory response may be both the cause and consequence of venous thromboembolism (VTE). In fact, several risk factors of VTE modulate thrombosis through inflammatory markers. Acute pulmonary embolism (PE) is burdened by a remarkable mortality rate, up to 34% in severely ill patients presenting with hemodynamic instability. Initial mortality risk stratification is based on hemodynamic instability. Patients with a situation of hemodynamic stability require immediate further risk assessment based on clinical, imaging, and circulating biomarkers, as well as the presence of comorbidities. Some inflammatory biomarkers have shown potential usefulness in the risk stratification of patients with VTE, especially acute PE. C-reactive protein on admission is associated with 30-day mortality and bleeding in VTE patients. P-selectin is associated with right ventricle dysfunction in PE patients and might be associated with VTE recurrences and the extension of thrombosis. Tissue factor microparticles are associated with VTE recurrence in cancer-associated thrombosis. Other inflammatory biomarkers present scarce evidence (inflammatory cytokines, erythrocyte sedimentation rate, fibrinogen, leukocyte count). In this manuscript, we will review the prognostic role of different inflammatory biomarkers available both for clinical practice and research in VTE patients.

Echocardiographic Manifestations in COVID-19: A Review.

COVID-19 has rapidly spread around the world and threatened global health. Although this disease mainly affects the respiratory system, there is increasing evidence that SARS-CoV-2 also has effects on the cardiovascular system. Echocardiography is a valuable tool in the assessment of cardiovascular disease. It is cost-effective, widely available and provides information that can influence management. Given the risk of personnel infection and equipment contamination during echocardiography, leading world societies have recommended performing echocardiography only when a clinical benefit is likely, favouring focussed evaluations and using smaller portable equipment. In the past months, multiple reports have described a wide pattern of echocardiographic abnormalities in patients with COVID-19. This review summarises these findings and discusses the possible mechanisms involved.

SPARCL1 as a biomarker of maladaptive right ventricular remodelling in pulmonary hypertension.

Aim: This study assessed the utility of SPARC-like protein 1 (SPARCL1) as a biomarker of maladaptive right ventricular (RV) function in patients with pulmonary hypertension (PH).Methods: In this prospective study, we examined SPARCL1 levels in 105 patients with adaptive (n = 34) and maladaptive RV (n = 32) pressure overload caused by PH, dilated cardiomyopathy (DCM, n = 18) with LVEF < 35% and preserved RV function and controls without LV or RV abnormalities (n = 21).Results: The median SPARCL1 concentration in patients with maladaptive RV function was higher than in those with adaptive RV function (p < 0.01), DCM (p < 0.001) or controls (p < 0.001). Patients with adaptive RV function had higher SPARCL1 concentrations than controls (p < 0.05), whereas there was no difference between adaptive RV and DCM. SPARCL1 showed good predictive power for maladaptive RV (AUC 0.77, p < 0.001) with an optimal cut-off value of 9.66 ng/ml. The TAPSE/PASP ratio was the only independent predictor of SPARCL1 ≥ 9.66 ng/ml in multivariable logistic regression analysis.Conclusion: SPARCL1 shows potential as novel biomarker of RV pathological remodelling and is associated with RV maladaptation and ventriculoarterial uncoupling in PH.

Right ventricular dysfunction is superior and sufficient for risk stratification by a pulmonary embolism response team.

Several risk stratification tools are available to predict short-term mortality in patients with acute pulmonary embolism (PE). The presence of right ventricular (RV) dysfunction is an independent predictor of mortality and may be a more efficient way to stratify risk for patients assessed by a Pulmonary Embolism Response Team (PERT). We evaluated 571 patients presenting with acute PE, then stratified them by the pulmonary embolism severity index (PESI), by the BOVA score, or categorically as low risk (no RV dysfunction by imaging), intermediate risk/submassive (RV dysfunction by imaging), or high risk/massive PE (RV dysfunction with sustained hypotension). Using imaging data to firstly define the presence of RV strain, and plasma cardiac biomarkers as additional evidence for myocardial dysfunction, we evaluated whether PESI, BOVA, or RV strain by imaging were more appropriate for determining patient risk by a PERT where rapid decision making is important. Cardiac biomarkers poorly distinguished between PESI classes and BOVA stages in patients with acute PE. Cardiac TnT and NT-proBNP easily distinguished low risk from submassive PE with an area under the curve (AUC) of 0.84 (95% CI 0.73-0.95, p < 0.0001), and 0.88 (95% CI 0.79-0.97, p < 0.0001), respectively. Cardiac TnT and NT-proBNP easily distinguished low risk from massive PE with an area under the curve (AUC) of 0.89 (95% CI 0.78-1.00, p < 0.0001), and 0.89 (95% CI 0.82-0.95, p < 0.0001), respectively. In patients with RV dysfunction, the predicted short-term mortality by PESI score or BOVA stage was lower than the observed mortality by a two-fold order of magnitude. The presence of RV dysfunction alone in the context of acute PE is sufficient for the purposes of risk stratification. More complicated risk stratification tools which require the consideration of multiple clinical variables may under-estimate short-term mortality risk.

High plasma adiponectin is associated with increased pulmonary blood flow and reduced right ventricular function in patients with pulmonary hypertension.

BACKGROUND: Adiponectin is a biomarker closely related to heart failure. However, its role in pulmonary hypertension remains unclear. In this study, we investigated the association between adiponectin and hemodynamic abnormalities, right ventricular function in patients with congenital heart disease associated pulmonary hypertension (CHD-PH). METHODS: Patients with CHD-PH were enrolled in this cross-sectional study. Linear regression analysis was performed to assess the association between adiponectin, N-terminal pro-Brain Natriuretic Peptide (NT-proBNP) and different clinical parameters. Results were depicted as beta-estimates(ß) with 95%-confidence intervals (95% CI). In addition, mediation and receiver operating characteristic curve analyses were used to analyze the relationships among adiponectin, NT-proBNP and right ventricular function. RESULTS: A total of 86 CHD-PH patients were included. The overall mean adiponectin concentration was 7.9 ± 5.8 µg/ml. Log adiponectin was positively correlated with pulmonary circulation index (ß = 2.2, 95% CI 0.5, 4.0), log NT-proBNP (ß = 0.22, 95% CI 0.04, 0.41) and inversely with the tricuspid annular plane systolic excursion (TAPSE, ß = -4.7, 95% CI -8.6, - 0.8). The mediation analysis revealed the association between NT-proBNP and TAPSE was fully mediated by adiponectin (total effect c = - 5.4, 95% CI -9.4, - 1.5, p = 0.013; direct effect c' = - 3.7, 95% CI -7.5, 0.1, p = 0.067). Additionally, the efficiency of adiponectin for detecting right ventricular dysfunction was not inferior to NT-proBNP (AUC = 0.84, 95% CI 0.67-1.00 vs AUC = 0.74, 95% CI 0.51-0.97, p = 0.23). CONCLUSIONS: Adiponectin is closely correlated with pulmonary blood flow and right ventricular function and may be a valuable biomarker for disease assessment in patients with pulmonary hypertension.

Prognostic value of right ventricular dysfunction or elevated cardiac biomarkers in patients with low-risk pulmonary embolism: a systematic review and meta-analysis.

AIMS: Patients with acute pulmonary embolism (PE) classified as low risk by the Pulmonary Embolism Severity Index (PESI), its simplified version (sPESI), or the Hestia criteria may be considered for early discharge. We investigated whether the presence of right ventricular (RV) dysfunction may aggravate the early prognosis of these patients. METHODS AND RESULTS: We did a systematic review and meta-analysis of studies including low-risk patients with acute PE to investigate the prognostic value of RV dysfunction. Diagnosis of RV dysfunction was based on echocardiography or computed tomography pulmonary angiography. In addition, we investigated the prognostic value of elevated troponin or natriuretic peptide levels. The primary outcome was all-cause mortality at 30 days or during hospitalization. We included 22 studies (N = 3295 low-risk patients) in the systematic review: 21 were selected for quantitative analysis. Early all-cause mortality rates in patients with vs. without RV dysfunction on imaging were 1.8% [95% confidence interval (CI) 0.9-3.5%] vs. 0.2% (95% CI 0.03-1.7%), respectively, [odds ratio (OR) 4.19, 95% CI 1.39-12.58]. For troponins, rates were 3.8% (95% CI 2.1-6.8%) vs. 0.5% (95% CI 0.2-1.3%), (OR 6.25, 95% CI 1.95-20.05). For natriuretic peptides, only data on early PE-related mortality were available: rates were 1.7% (95% CI 0.4-6.9%) vs. 0.4% (95% CI 0.1-1.1%), (OR 3.71, 95% CI 0.81-17.02). CONCLUSIONS: In low-risk patients with acute PE, the presence of RV dysfunction on admission was associated with early mortality. Our results may have implications for the management of patients who appear at low risk based on clinical criteria alone, but present with RV dysfunction as indicated by imaging findings or laboratory markers.

Right ventricular oxygen delivery as a determinant of right ventricular functional reserve during exercise in juvenile swine with chronic pulmonary hypertension.

Assessing right ventricular (RV) functional reserve is important for determining clinical status and prognosis in patients with pulmonary hypertension (PH). In this study, we aimed to establish RV oxygen (O2) delivery as a determinant for RV functional reserve during exercise in swine with chronic PH. Chronic PH was induced by pulmonary vein banding (PVB), with sham operation serving as control. RV function and RV O2 delivery were measured over time in chronically instrumented swine, up to 12 wk after PVB at rest and during exercise. At rest, RV afterload (pulmonary artery pressure and arterial elastance) and contractility (Ees and dP/dtmax) were higher in PH compared with control with preserved cardiac index and RV O2 delivery. However, RV functional reserve, as measured by the exercise-induced relative change (Δ) in cardiac index, dP/dtmax, and end-systolic elastance (Ees), was decreased in PH, and RV pulmonary arterial coupling was lower both at rest and during exercise in PH. Furthermore, the increase in RV O2 delivery was attenuated in PH during exercise principally due to a lower systolic coronary blood flow in combination with an attenuated increase in aorta pressure while arterial O2 content was not significantly altered in PH. Moreover, RV O2 delivery reserve correlated with RV functional reserve, Δcardiac index (r2 = 0.85), ΔdP/dtmax (r2 = 0.49), and ΔEes (r2 = 0.70), all P < 0.05. The inability to sufficiently increase RV O2 supply to meet the increased O2 demand during exercise is principally due to the reduced RV perfusion relative to healthy control values and likely contributes to impaired RV contractile function and thereby to the limited exercise capacity that is commonly observed in patients with PH.NEW & NOTEWORTHY Impaired right ventricular (RV) O2 delivery reserve is associated with reduced RV functional reserve during exercise in a swine model of pulmonary hypertension (PH) induced by pulmonary vein banding. Our data suggest that RV function and exercise capacity might be improved by improving RV O2 delivery.

Right ventricular remodeling in response to volume overload in fetal sheep.

The fetal myocardium is known to be sensitive to hemodynamic load, responding to systolic overload with cellular hypertrophy, proliferation, and accelerated maturation. However, the fetal cardiac growth response to primary volume overload is unknown. We hypothesized that increased venous return would stimulate fetal cardiomyocyte proliferation and terminal differentiation, particularly in the right ventricle (RV). Vascular catheters and pulmonary artery flow probes were implanted in 16 late-gestation fetal sheep: a right carotid artery-jugular vein (AV) fistula was surgically created in nine fetuses, and sham operations were performed on seven fetuses. Instrumented fetuses were studied for 1 wk before hearts were dissected for component analysis or cardiomyocyte dispersion for cellular measurements. Within 1 day of AV fistula creation, RV output was 20% higher in experimental than sham fetuses ( P < 0.0001). Circulating atrial natriuretic peptide levels were elevated fivefold in fetuses with an AV fistula ( P < 0.002). On the terminal day, RV-to-body weight ratios were 35% higher in the AV fistula group ( P < 0.05). Both left ventricular and RV cardiomyocytes grew longer in fetuses with an AV fistula ( P < 0.02). Cell cycle activity was depressed by >50% [significant in left ventricle ( P < 0.02), but not RV ( P < 0.054)]. Rates of terminal differentiation were unchanged. Based on these studies, we speculate that atrial natriuretic peptide suppressed fetal cardiomyocyte cell cycle activity. Unlike systolic overload, fetal diastolic load appears to drive myocyte enlargement, but not cardiomyocyte proliferation or maturation. These changes could predispose to RV dysfunction later in life. NEW & NOTEWORTHY Adaptation of the fetal heart to changes in cardiac load allows the fetus to maintain adequate blood flow to its systemic and placental circulations, which is necessary for the well-being of the fetus. Addition of arterial-venous fistula flow to existing venous return increased right ventricular stroke volume and output. The fetal heart compensated by cardiomyocyte elongation without accelerated cellular maturation, while cardiomyocyte proliferation decreased. Even transient volume overload in utero alters myocardial structure and cardiomyocyte endowment.

A potential contribution of trappin-2 to the development of vasculopathy in systemic sclerosis.

BACKGROUND: Trappin-2/pre-elafin is an endogenous inhibitor of human neutrophil elastase involved in inflammation, innate immunity and vascular remodelling, which consist of the complex pathological process of systemic sclerosis (SSc). OBJECTIVES: To clarify the potential role of trappin-2 in SSc. METHODS: Serum trappin-2 levels were determined by enzyme-linked immunosorbent assay in 51 SSc and 18 healthy subjects. Trappin-2 expression was evaluated in SSc lesional skin and cultured endothelial cells treated with FLI1 siRNA by immunohistochemistry, reverse transcription-real-time PCR and/or immunoblotting. Friend leukaemia virus integration 1 (Fli1) binding to the PI3 promoter was assessed by chromatin immunoprecipitation. RESULTS: Since serum trappin-2 levels inversely correlated with estimated glomerular filtration rate in SSc patients with renal dysfunction, SSc patients with normal renal function were analysed. Although serum trappin-2 levels were comparable between diffuse cutaneous SSc, limited cutaneous SSc and control subjects, the prevalence of digital ulcers or elevated right ventricular systolic pressure (RVSP) was significantly higher in SSc patients with elevated serum trappin-2 levels than in those with normal levels. Furthermore, serum trappin-2 levels were significantly increased in SSc patients with digital ulcers or elevated RVSP compared to those without. Moreover, serum trappin-2 levels positively correlated with RVSP values in SSc patients. Importantly, trappin-2 expression was enhanced in small vessels of SSc lesional skin. In cultured endothelial cells, trappin-2 expression was elevated by gene silencing of FLI1 at mRNA and protein levels and Fli1 occupied the PI3 promoter. CONCLUSIONS: Endothelial trappin-2 up-regulation partially due to Fli1 deficiency can be associated with the development of SSc vasculopathy.

Velocity vector imaging echocardiography and NT-proBNP study of fetal cardiac function in pregnancy-induced maternal hypertension.

PURPOSE: To investigate whether acute and transient pressure overload in patients with pregnancy-induced hypertension affects cardiac function in fetuses. METHODS: We enrolled 104 singleton pregnant women with gestational ages ranging 30 to 33 weeks, visiting for prenatal care. Among them, 34 had gestational hypertension (GH), 32 had preeclampsia (PE), and 38 were healthy and formed the control group. Conventional echocardiographic and velocity vector imaging (VVI) variables were prospectively collected. Blood levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) were measured from cord blood drawn at birth. RESULTS: The fetuses of mothers with preeclampsia had significantly lower left (LV) and right ventricle (RV) diastolic strain rate (SRd) and RV strain (S) and systolic strain rate (SRs) than controls. LV and RV S, SRd, and SRS were not different in fetuses of mothers with GH and controls. The NT-proBNP levels were higher in fetuses of patients with PE than in GH and controls. CONCLUSIONS: In the third trimester of pregnancy, fetal biventricular function and NT-proBNP levels are not significantly influenced by GH. Fetuses of mothers with PE present signs of LV and RV diastolic dysfunction, right ventricular systolic dysfunction, and elevated NT-pro-BNP levels. VVI echocardiography appears more sensitive than conventional echocardiography to evaluate fetal cardiac function.

D-Dimer and thrombus burden in acute pulmonary embolism.

BACKGROUND: Thrombus burden in pulmonary embolism (PE) is associated with higher D-Dimer-levels and poorer prognosis. We aimed to investigate i) the influence of right ventricular dysfunction (RVD), deep venous thrombosis (DVT), and high-risk PE-status on D-Dimer-levels and ii) effectiveness of D-Dimer to predict RVD in normotensive PE patients. METHODS: Overall, 161 PE patients were analyzed retrospectively, classified in 5 subgroups of thrombus burden according to clinical indications and compared regarding D-Dimer-levels. Linear regression models were computed to investigate the association between D-Dimer and the groups. In hemodynamically stable PE patients, a ROC curve was calculated to assess the effectiveness of D-Dimer for predicting RVD. RESULTS: Overall, 161 patients (60.9% females, 54.0% aged >70 years) were included in this analysis. The D-Dimer-level was associated with group-category in a univariate linear regression model (ß 0.050 (95%CI 0.002-0.099), P = .043). After adjustment for age, sex, cancer, and pneumonia in a multivariate model we observed an association between D-Dimer and group-category with borderline significance (ß 0.047 (95%CI 0.002-0.096), P = .058). The Kruskal-Wallis test demonstrated that D-Dimer increased significantly with higher group-category. In 129 normotensive patients, patients with RVD had significantly higher D-Dimer values compared to those without (1.73 (1.11/3.48) vs 1.17 (0.65/2.90) mg/l, P = .049). A ROC curve showed an AUC of 0.61, gender non-specific, with calculated optimal cut-off of 1.18 mg/l. Multi-variate logistic regression model confirmed an association between D-Dimer >1.18 mg/l and RVD (OR2.721 (95%CI 1.196-6.190), P = .017). CONCLUSIONS: Thrombus burden in PE is related to elevated D-Dimer levels, and D-Dimer values >1.18 mg/l were predictive for RVD in normotensive patients. D-Dimer levels were influenced by DVT, but not by cancer, pneumonia, age, or renal impairment.

Rapid on-site evaluation of routine biochemical parameters to predict right ventricular dysfunction in and the prognosis of patients with acute pulmonary embolism upon admission to the emergency room.

INTRODUCTION: Patients with acute pulmonary embolism(APE)who present with right ventricular dysfunction (RVD) have a worse prognosis. This study aimed to evaluate the value of routine biochemical parameters in predicting RVD and 30-day mortality in patients with APE. METHODS: We retrospectively collected the clinical data for 154 enrolled patients, including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), D-dimer, cardiac troponin I (cTnI), and N-terminal pro-brain natriuretic peptide (NT-proBNP). We analyzed the correlation between RVD and the parameters and conducted a receiver operating characteristic (ROC) curve to confirm the cut-off values for predicting RVD and 30-day mortality. Formulas were built with relevant parameters to predict RVD and 30-day mortality. RESULTS: Age, NLR, PLR, D-dimer, the ratio of cTnI (+), and NT-proBNP (+) were significantly higher in RVD (+) patients. The ratio of cTnI (+) and NT-proBNP (+) in 30-day mortality (+) patients was significantly higher than that in 30-day mortality (-) patients. According to the logistic regression analysis, NLR, cTnI (+), and NT-proBNP (+) correlated with RVD. The formula for the RVD risk score is 0.072 × NLR+1.460 × NT-proBNP (+)+2.113 × cTnI (+), and the area under the curve (AUC) = 0.890 (95% CI: 0.839-0.941, P = .001). The formula for the 30-day mortality risk score is 0.115 × NLR + 2.046 × NT-proBNP (+) + 1.946 × cTnI (+) -0.016 × PLR, and the AUC = 0.903 (95% CI: 0.829-0.976, P = .001). CONCLUSIONS: The rapid on-site evaluation of routine biochemical parameters, including NLR, cTnI, and NT-proBNP levels, and the formula developed using these parameters are valuable for predicting RVD and 30-day mortality in patients with APE.

Subclinical right ventricular dysfunction in intermittent and persistent mildly asthmatic children on tissue Doppler echocardiography and serum NT-proBNP: Observational study.

BACKGROUND: Bronchial asthma may lead to pulmonary hypertension, right ventricular (RV) dysfunction, and cor pulmonale due to elevated afterload on the RV later in life. The aim of this study was to determine whether serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) might serve as a biomarker for detecting subclinical RV dysfunction using echocardiography during the early stages of bronchial asthma. METHODS: Sixty-eight pediatric patients with asthma (asthma group) and 69 age- and sex-matched healthy children (control group) were enrolled. The study was conducted in a tertiary woman and child diseases education and research hospital from January 2013 to December 2013. RV function (2-D and tissue-Doppler echocardiography), pulmonary function (spirometry) and serum NT-proBNP concentration were evaluated. RESULTS: Mean age was 10.5 ± 2.8 years in the asthma group and 10.2 ± 2.7 years in the control group (P = 0.522). RV diastolic function was significantly decreased in the asthma group (ratio of tricuspid lateral annular early diastolic peak velocity to tricuspid lateral annular late diastolic peak velocity [E'/A'], 1.29 ± 0.68 vs 1.74 ± 0.89, P = 0.001). RV myocardial performance index was significantly higher in the asthma group than in the control group (0.28 ± 0.06 vs 0.24 ± 0.07, respectively; P = 0.003). Finally, serum NT-proBNP concentration was significantly higher in the asthma group than in the control group (292.3 ± 142.2 pg/mL vs 208.2 ± 70.1 pg/mL, respectively; P = 0.003). CONCLUSION: Increased serum NT-proBNP is associated with subclinical RV dysfunction in asthmatic children. RV function is significantly affected in children with bronchial asthma.

[Diagnostic value of serum cardiac biomarkers for right ventricular dysfunction in non-high-risk patients with acute pulmonary thromboembolism].

Objective: To investigate the diagnostic value of N-terminal pro-brain natriuretic peptide (NT-proBNP) and troponin Ⅰ (TnI) for detecting right ventricular dysfunction (RVD) in patients with non-high-risk acute pulmonary thromboembolism (APE). Methods: A retrospective analysis was performed in 96 adult patients [44 males, 52 females, aged (61±14) years] with non-high-risk APE from January 2015 to June 2016. All patients were divided into RVD group and non-RVD group according to whether there was right ventricular enlargement on echocardiography. The baseline data, serumTnI and NT-proBNP levels were compared between the 2 groups and the diagnostic value of the 2 cardiac markers for RVD was analyzed. Results: There were no significant differences in age, gender, body mass index between the 2 groups (P>0.05). The creatinine clearance rate of the RVD group was lower than that of the non-RVD group [96.4 (77.5,99.6) vs 101.7 (95.1,106.5), P=0.021]. NT-proBNP [2 300 (1 056,3 396) vs 188 (61,535), P<0.01] and TnI [0.13 (0.09,0.25) vs 0.00 (0.00,0.02), P<0.01] were significant higher in the RVD group than in the non-RVD group. The univariate logistic regression analyses showed that NT-proBNP (per 100 ng/L, OR 1.199, 95%CI 1.117-1.287), TnI (per 0.01 µg/L, OR 1.164, 95%CI 1.079-1.256) and creatinine clearance rate (OR 0.968, 95% CI 0.938-0.998) were significantly associated with RVD. Multivariate regression analysis showed that NT-proBNP (per 100 ng/L, OR 1.155, 95%CI 1.074-1.241) and TnI (per 0.01 µg/L, OR 1.079, 95% CI 1.011-1.151) were independently associated with RVD. The areas under the ROC curve (AUC) of NT-proBNP, TnI, and the combination of them were 0.908 (95% CI 0.841-0.976), 0.896 (95% CI 0.826-0.966) and 0.925 (95% CI 0.862-0.988), respectively. The cut-off value of NT-proBNP was 503.5 ng/L, with a sensitivity of 85.7%, specificity of 75.4%, positive predictive value (PPV) of 66.7% and negative predictive value (NPV) of 90.2%.The cut-off value of TnI was 0.05 µg/L, and the sensitivity, specificity, PPV and NPV was 80.0%, 86.9%, 77.8% and 88.3%, respectively. The optimal probability derived from the logistic regression model in which the 2 biomarkers were the independent variables was 0.779, with a sensitivity, specificity, PPV and NPV of 65.7%, 96.7%, 92.0%, 83.1%, respectively. Conclusion: Both NT-proBNP and TnI had preferably good diagnostic value for RVD in patients with non-high-risk APE, but their clinical application needed comprehensive evaluation combined with the overall manifestations of the patients and experimental methods. The diagnostic value was higher when the 2 biomarkers were evaluated together.

Early Development of Right Ventricular Ischemic Lesions in a Novel Large Animal Model of Acute Right Heart Failure in Chronic Thromboembolic Pulmonary Hypertension.

BACKGROUND: Our aim was to develop a model of acute right heart failure (ARHF) in the setting of pulmonary hypertension and to characterize acute right ventricular lesions that develop early after hemodynamic restoration. METHODS AND RESULTS: We used a described piglet model of chronic pulmonary hypertension (cPH) induced by pulmonary artery occlusions. We induced ARHF in animals with cPH (ARHF-cPH group, n = 9) by volume loading and iterative acute pulmonary embolism until hemodynamic compromise followed by dobutamine infusion for hemodynamic restoration before sacrifice for right ventricular tissue evaluation. The median duration of ARHF before sacrifice was 162 (135-189) minutes. Although ventriculoarterial coupling (measured with multibeat pressure-volume loops) and stroke volume decreased after iterative pulmonary embolism and improved with dobutamine, relative pulmonary to systemic pressure increased by 2-fold and remained similarly increased with dobutamine. Circulating high-sensitivity troponin I increased after hemodynamic restoration. We found an increase in right ventricular subendocardial and subepicardial focal ischemic lesions and in expression of autophagy-related protein LC3-II (Western blot) in the ARHF-cPH group compared with the cPH (n = 5) and control (n = 5) groups. CONCLUSIONS: We developed and phenotyped a novel large animal model of ARHF on cPH in which right ventricular ischemic lesions were observed early after hemodynamic restoration.