Plasma Levels of Soluble CD146 Reflect the Severity of Pulmonary Congestion Better Than Brain Natriuretic Peptide in Acute Coronary Syndrome

BACKGROUND: Acute heart failure negatively affects short-term outcomes of patients with acute coronary syndrome (ACS). Therefore, reliable and non-invasive assessment of pulmonary congestion is needed to select patients requiring more intensive monitoring and therapy. Since plasma levels of natriuretic peptides are influenced by myocardial ischemia, they might not reliably reflect congestion in the context of ACS. The novel endothelial biomarker, soluble CD146 (sCD146), presents discriminative power for detecting the cardiac origin of acute dyspnea similar to that of natriuretic peptides and is associated with systemic congestion. We evaluated the performance of sCD146 for the assessment of pulmonary congestion in the early phase of ACS. METHODS: One thousand twenty-one consecutive patients with ACS were prospectively enrolled. Plasma levels of sCD146, brain natriuretic peptide (BNP), and high-sensitive troponin T were measured within 24 hr after the onset of chest pain. Pulmonary congestion on chest radiography was determined and classified in three groups according to the degree of congestion. RESULTS: Nine hundred twenty-seven patients with ACS were analyzed. Ninety-two (10%) patients showed signs of pulmonary edema on chest radiography. Plasma levels of sCD146 reflected the radiological severity of pulmonary congestion. Higher plasma levels of sCD146 were associated with the worse degree of pulmonary congestion. In contrast to BNP, sCD146 levels were not affected by the level of troponin T. CONCLUSIONS: The novel endothelial biomarker, sCD146, correlates with radiological severity of pulmonary congestion in the early phase of ACS and, in contrast to BNP, is not affected by the amount of myocardial cell necrosis

GRACE Score among Six Risk Scoring Systems (CADILLAC, PAMI, TIMI, Dynamic TIMI, Zwolle) Demonstrated the Best Predictive Value for Prediction of Long-Term Mortality in Patients with ST-Elevation Myocardial Infarction.

To compare the prognostic accuracy of six scoring models for up to three-year mortality and rates of hospitalisation due to acute decompensated heart failure (ADHF) in STEMI patients.A total of 593 patients treated with primary PCI were evaluated. Prospective follow-up of patients was ≥3 years. Thirty-day, one-year, two-year, and three-year mortality rates were 4.0%, 7.3%, 8.9%, and 10.6%, respectively. Six risk scores--the TIMI score and derived dynamic TIMI, CADILLAC, PAMI, Zwolle, and GRACE--showed a high predictive accuracy for six- and 12-month mortality with area under the receiver operating characteristic curve (AUC) values of 0.73-0.85. The best predictive values for long-term mortality were obtained by GRACE. The next best-performing scores were CADILLAC, Zwolle, and Dynamic TIMI. All risk scores had a lower prediction accuracy for repeat hospitalisation due to ADHF, except Zwolle with the discriminatory capacity for hospitalisation up to two years (AUC, 0.80-0.83).All tested models showed a high predictive value for the estimation of one-year mortality, but GRACE appears to be the most suitable for the prediction for a longer follow-up period. The tested models exhibited an ability to predict the risk of ADHF, especially the Zwolle model

Prognostic Value of Pentraxin-3 Level in Patients with STEMI and Its Relationship with Heart Failure and Markers of Oxidative Stress

Objective. Pentraxin-3 (PTX3) appears to have a cardioprotective effect through a positive influence against postreperfusion damage. This study assesses the prognostic value of PTX3 level and its relationship with clinical parameters and markers of oxidative stress and nitric oxide metabolism in patients with ST-elevation myocardial infarction (STEMI). Methods. Plasma/serum levels of several biomarkers of inflammation and oxidative stress and nitrite/nitrate were assessed upon admission and 24 h after STEMI onset in patients treated by primary percutaneous coronary intervention. Results. ROC analysis showed that plasma PTX3 at 24 h was a strong predictor of 30-day and 1-year mortality and independent predictor of combined end-point of left ventricle dysfunction or mortality in 1 year. The inflammatory response expressed by PTX3 had a significant relationship with age, heart failure, infarct size, impaired flow in the infarct-related artery, and renal function and positively correlated with neopterin, TNF-α, 8-hydroxy-2′-deoxyguanosine, and nitrite/nitrate. Conclusions. Plasma PTX3 at 24 h after STEMI onset is a strong predictor of 30-day and 1-year mortality. PTX3 as a single biomarker is comparable with currently used scoring systems (TIMI or GRACE) or B-type natriuretic peptide. PTX3 is also an independent predictor of combined end-point of left ventricle dysfunction or mortality in 1 year

rs2076295 variants influence nintedanib and pirfenidone outcomes in idiopathic pulmonary fibrosis: a pilot study

Background: The antifibrotic drugs nintedanib and pirfenidone are used for the treatment of idiopathic pulmonary fibrosis (IPF). We analysed the association of common profibrotic polymorphisms in MUC5B (mucin 5B, rs35705950) and DSP (desmoplakin, rs2076295) on antifibrotic treatment outcomes in IPF. Methods: MUC5B rs35705950 and DSP rs2076295 were assessed in IPF patients ( n  = 210, 139 men/71 women) from the Czech EMPIRE registry and age- or sex-matched healthy individuals ( n  = 205, 125 men/80 women). Genetic data were collated with overall survival (OS), acute exacerbation episodes, worsening lung function and antifibrotic treatment. Results: We confirmed overexpression of the MUC5B rs35705950*T allele (55.2% versus 20.9%, p  < 0.001) and the DSP rs2076295*G allele (80.4% versus 68.3%, p  < 0.001) in IPF compared with controls. On antifibrotic drugs, lower mortability was observed in IPF patients with DSP G* allele ( p  = 0.016) and MUC5B T* allele ( p  = 0.079). Carriers of the DSP rs2076295*G allele benefitted from nintedanib treatment compared with TT genotype by a longer OS [hazard ratio (HR) = 7.99; 95% confidence interval (CI) = 1.56–40.90; p  = 0.013] and a slower decline in lung function (HR = 8.51; 95% CI = 1.68–43.14; p  = 0.010). Patients with a TT genotype (rs2076295) benefitted from treatment with pirfenidone by prolonged OS ( p  = 0.040; HR = 0.35; 95% CI = 0.13–0.95) compared with nintedanib treatment. Both associations were confirmed by cross-validation analysis. After stratifying by MUC5B rs35705950*T allele carriage, no difference in treatment outcome was observed for nintedanib or pirfenidone ( p  = 0.784). In the multivariate model, smoking, age, forced vital capacity (FVC) and DL CO (diffuse lung capacity) at the IPF diagnosis were associated with survival. Conclusion: Our real-world study showed that IPF patients with MUC5B T* allele or DSP G* allele profit from antifibrotic treatment by lower mortability. Moreover, carriers of the DSP rs2076295*G allele benefit from treatment with nintedanib, and TT genotype from treatment with pirfenidone. MUC5B rs35705950 did not impact the outcome of treatment with either nintedanib or pirfenidone. Our single-registry pilot study should be confirmed with an independent patient cohort

Baseline characteristics of patients and medical therapy upon hospital admission.

<p>*Recurrent MI, stroke, major bleed, CHF/shock, arrhythmia, renal failure;</p><p>MI—myocardial infarction, ACEI—angiotensin-converting enzyme inhibitor, ARB—angiotensin II receptor blockers, PCI—percutaneous coronary intervention, CABG—coronary artery bypass grafting, TIA—transient ischaemic attack, AHF—acute heart failure.</p><p>Baseline characteristics of patients and medical therapy upon hospital admission.</p

Predictive accuracy of scoring models for rehospitalisation due to ADHF during a three-year follow-up period.

<p>Predictive accuracy of scoring models for rehospitalisation due to ADHF during a three-year follow-up period.</p

Characteristics of laboratory tests and invasive procedures.

<p>IRA—infarct-related artery, LAD—left anterior descending artery, CABG—coronary artery bypass graft, RCA—right coronary artery, RPLD—ramus posterolateral dexter, RIVP—ramus interventricularis posterior, RCx—ramus circumflexus, RMS—ramus marginalis sinister, RIM—ramus intermedius, RD—ramus diagonalis, BNP—brain natriuretic peptide, LVEF—left ventricular ejection fraction.</p><p>Characteristics of laboratory tests and invasive procedures.</p