Plasma N-terminal pro-brain natriuretic peptide concentrations may help to identify patients with very low-risk acute pulmonary embolism: A preliminary study.

BACKGROUND: Patients with an acute pulmonary embolism (APE) are a heterogeneous group, and some of them may benefit from early discharge and an ambulatory care referral. We aimed to evaluate the use of N-terminal pro-brain natriuretic peptide (NT-proBNP) plasma level assessment in patients with low-risk APE based on clinical findings (0 points on the simplified Pulmonary Embolism Severity Index (sPESI)). MATERIAL AND METHODS: Preliminary analysis of an ongoing prospective study including 1,151 normotensive patients with at least a segmental APE. In the final analysis, 348 patients with a 0-point sPESI were included. Blood samples were collected within the first 24 h of admission. The clinical endpoint (CE) included APE-related mortality and/or rescue thrombolysis in patients with clinical deterioration. RESULTS: Clinical endpoints occurred in 3 patients who had higher plasma NT-proBNP levels than study participants with a favorable clinical course (164 [64-650] pg/mL compared to 2,930 [2,285.5-13,965] pg/mL; p = 0.01). Receiver operating characteristic (ROC) analysis showed that the area under the curve (AUC) for NT-proBNP for the prediction of the CEs was 0.918 (95% confidence interval [95% CI]: 0.831-1.00; p = 0.013). We defined the cutoff value of NT-proBNP at ≥1,641 pg/mL. CONCLUSIONS: Among subjects with 0 points on the sPESI, those with concentrations of NT-proBNP exceeding 1,641 pg/mL might require closer attention; remaining patients could be considered candidates for outpatient treatment. However, these findings warrant further investigation in a large, prospective group of patients.

Heart Rate Variability Impairment Is Associated with Right Ventricular Overload and Early Mortality Risk in Patients with Acute Pulmonary Embolism.

The association between heart rate variability (HRV) and mortality risk of acute pulmonary embolism (APE), as well as its association with right ventricular (RV) overload is not well established. We performed an observational study on consecutive patients with confirmed APE. In the first 48 h after admission, 24 h Holter monitoring with assessment of time-domain HRV, echocardiography and NT-proBNP (N-terminal pro-B-type natriuretic peptide) measurement were performed in all participants. We pre-examined 166 patients: 32 (20%) with low risk of early mortality, 65 (40%) with intermediate-low, 65 (40%) with intermediate-high, and 4 (0.02%) in the high risk category. The last group was excluded from further analysis due to sample size, and finally, 162 patients aged 56.3 ± 18.5 years were examined. We observed significant correlations between HRV parameters and echocardiographic signs of RV overload. SDNN (standard deviation of intervals of all normal beats) correlated with echocardiography-derived RVSP (right ventricular systolic pressure; r = -0.31, p = 0.001), TAPSE (tricuspid annulus plane systolic excursion; r = 0.21, p = 0.033), IVC (inferior vena cava diameter; r = -0.27, p = 0.002) and also with NT-proBNP concentration (r = -0.30, p = 0.004). HRV indices were also associated with APE risk stratification, especially in the low-risk category (r = 0.30, p = 0.004 for SDNN). Univariate and multivariate analyses confirmed that SDNN values were associated with signs of RV overload. In conclusion, we observed a significant association between time-domain HRV parameters and echocardiographic and biochemical signs of RV overload. Impaired HRV parameters were also associated with worse a clinical risk status of APE.

Plasma Troponins Identify Patients with Very Low-Risk Acute Pulmonary Embolism.

INTRODUCTION: Although in the non-vitamin K oral anticoagulants (NOAC) era majority of low-risk acute pulmonary embolism (APE) patients can be treated at home, identifying those at very low risk of clinical deterioration may be challenging. We aimed to propose the risk stratification algorithm in sPESI 0 point APE patients, allowing them to select candidates for safe outpatient treatment. MATERIALS AND METHODS: Post hoc analysis of a prospective study of 1151 normotensive patients with at least segmental APE. In the final analysis, we included 409 sPESI 0 point patients. Cardiac troponin assessment and echocardiographic examination were performed immediately after admission. Right ventricular dysfunction was defined as the right ventricle/left ventricle ratio (RV/LV) > 1.0. The clinical endpoint (CE) included APE-related mortality and/or rescue thrombolysis and/or immediate surgical embolectomy in patients with clinical deterioration. RESULTS: CE occurred in four patients who had higher serum troponin levels than subjects with a favorable clinical course (troponin/ULN: 7.8 (6.4-9.4) vs. 0.2 (0-1.36) p = 0.000). Receiver operating characteristic (ROC) analysis showed that the area under the curve for troponin in the prediction of CE was 0.908 (95% CI 0.831-0.984; p < 0.001). We defined the cut-off value of troponin at >1.7 ULN with 100% PPV for CE. In univariate and multivariate analysis, elevated serum troponin level was associated with an increased risk of CE, whereas RV/LV > 1.0 was not. CONCLUSIONS: Solely clinical risk assessment in APE is insufficient, and patients with sPESI 0 points require further assessment based on myocardial damage biomarkers. Patients with troponin levels not exceeding 1.7 ULN constitute the group of "very low risk" with a good prognosis.

D-dimer levels enhance the discriminatory capacity of bleeding risk scores for predicting in-hospital bleeding events in acute pulmonary embolism.

INTRODUCTION: Bleeding is a major complication of anticoagulation in acute pulmonary embolism (APE) while estimating individual bleeding risk remains challenging. Elevated D-dimer levels (DD) have been shown to predict bleeding events. OBJECTIVES: (1) direct comparison of the capacity of bleeding risk prediction scores (VTE-BLEED, RIETE, HAS-BLED, HEMORR2HAGES) to prognosticate in-hospital bleeding events in the acute phase of APE in a real-life population of APE patients;(2) augmentation of the discriminative capacity of fore mentioned scores with DD. MATERIALS: Post-hoc analysis of a prospective observational study. DD levels were measured using the VIDAS D-dimer Exclusion test. Receiver operating characteristic curves, areas under the curve (AUC) for bleeding prediction were calculated for scores and DD. Bleeding scores+DD were compared using an established index quantifying the reclassification of patients (net reclassification index, NRI). RESULTS: 310 APE patients were included. 35(11.3%) bleeding events occurred (hematomas, GI, urinary tract, retroperitoneal, uterine, CNS, respiratory tract): 17 major (MB) and 18 clinically-relevant non-major bleedings (CRNMB), none were fatal. All scores had satisfactory AUCs (0.754-0.767), except HAS-BLED (AUC = 0.512; 0.455-0.569). DD were higher in patients with bleeding events (29,911 ng/ml vs. 4805 ng/ml, p = .031), AUC 0.621(0.520-0.721), p = .02. DD = 5750 ng/ml was characterized by OR = 2.3(95%CI 1.05-5.0) for all bleeding events. Adding DD improved the discriminatory capacity of tested scores in the non-high risk of bleeding category, NRI 0.07-03. CONCLUSIONS: Of the tested scores RIETE, HEMORR2HAGES, VTE-BLEED performed best at identifying APE patients at risk of in-hospital bleeding complications. DD levels may predict in-hospital bleeding events and may improve identifying patients classified as non-high risk who experience bleeding complications.

Beyond the boundaries of cardiology: Still untapped anticancer properties of the cardiovascular system-related drugs.

Cardiovascular disorders and cancer are the most common chronic diseases, frequently coexistent and interdependent. Based on their common etiology and molecular background, the hypothesis on the potential anti-cancer activity of cardiological drugs appeared, mainly in response to the necessity of increasing the efficacy of existing oncological treatment schemes. In fact, cancer is known to induce the profound malfunction of typical cardiovascular-regulating systems, including the renin-angiotensin system, sympathetic nervous system and coagulation cascade. Therefore, in this review we have analyzed the available preclinical and clinical data on the repurposing potential of the following classes of cardiology drugs: angiotensin converting-enzyme inhibitors, angiotensin receptor blockers, beta blockers, statins and heparins. All of them have been shown to attenuate cancer development: the renin-angiotensin system inhibitors primarily by reducing inflammation, angiogenesis and immunosuppression, beta blockers by repressing migration and metastasis, heparins by decreasing metastasis and statins by influencing cell growth, apoptosis, migration and angiogenesis. We also have discussed the specific mechanisms of anticancer action for each group and then suggestions on their potential clinical use have been presented. Nonetheless, the establishment of strong indications for repurposing procedure, both individually and collectively, is unfeasible at the moment due to insufficient clinical data and therefore further investigations in this context are necessary and encouraged.

Can cardiovascular drugs support cancer treatment? The rationale for drug repurposing.

Research on the concept of biological overlap between cardiovascular and oncological diseases is gaining momentum. In fact, in both conditions, the malfunction of common regulatory mechanisms, such as the renin-angiotensin system (RAS), sympathetic nervous system (SNS), coagulation cascade, sodium-potassium ATP-ases, and mevalonate pathway, occurs. Thus, targeting these mechanisms with well-known cardiology drugs, including angiotensin-converting enzyme inhibitors (ACE-Is), angiotensin receptor blockers (ARBs), ß-adrenergic receptor blockers, statins, cardiac glycosides (CGs), and low-molecular-weight heparins (LMWHs), could be a novel, promising adjuvant strategy in cancer management. Thus, here we discuss the idea of repurposing cardiology drugs in oncology based on available preclinical and clinical data.