atrial-natriuretic-factor and ST-Elevation-Myocardial-Infarction

During the last three decades, timely myocardial reperfusion using either thrombolytic therapy or primary percutaneous intervention (pPCI) has allowed amazing improvements in outcomes with a more than halving in 1-year ST-elevation myocardial infarction (STEMI) mortality. However, mortality and left ventricle (LV) remodeling remain substantial in these patients. As such, novel therapeutic interventions are required to reduce myocardial infarction size, preserve LV systolic function, and improve survival in reperfused-STEMI patients. Myocardial ischemia-reperfusion injury (MIRI) prevention represents the main goal to reach in order to reduce STEMI mortality. There is currently no effective therapy for MIRI prevention in STEMI patients. A significant reason for the weak and inconsistent results obtained in this field may be the presence of multiple, partially redundant, mechanisms of cell death during ischemia-reperfusion, whose relative importance may depend on the conditions. Therefore, it is always more recognized that it is important to consider a "multi-targeted cardioprotective therapy", defined as an additive or synergistic cardioprotective agents or interventions directed to distinct targets with different timing of application (before, during, or after pPCI). Given that some neprilysin (NEP) substrates (natriuretic peptides, angiotensin II, bradykinin, apelins, substance P, and adrenomedullin) exert a cardioprotective effect against ischemia-reperfusion injury, it is conceivable that antagonism of proteolytic activity by this enzyme may be considered in a multi-targeted strategy for MIRI prevention. In this review, by starting from main pathophysiological mechanisms promoting MIRI, we discuss cardioprotective effects of NEP substrates and the potential benefit of NEP pharmacological inhibition in MIRI prevention.

Topics: Adrenomedullin; Aminobutyrates; Angiotensin II; Animals; Apelin; Atrial Natriuretic Factor; Biphenyl Compounds; Bradykinin; Cardiotonic Agents; Drug Combinations; Gene Expression Regulation; Humans; Mice; Myocardial Reperfusion Injury; Neprilysin; ST Elevation Myocardial Infarction; Substance P; Survival Analysis; Tetrazoles; Valsartan; Ventricular Remodeling

Atrial fibrillation (AF) is common following ST-segment elevation myocardial infarction (STEMI). Increased blood levels of mid regional pro atrial natriuretic peptide (MR-proANP) have been associated with a greater risk of incident AF. However, knowledge of the value of MR-proANP in predicting incident AF after STEMI is sparse. To assess whether MR-proANP measured at admission is associated with development of incident AF in patients with STEMI. 673 STEMI patients with no history of AF treated with primary percutaneous coronary intervention (pPCI) were prospectively enrolled from September 2006 to December 2008. Blood samples were drawn before the procedure. MR-proANP was measured by an automated processing assay. End point was incident AF. Median follow-up time was 5.5 years (interquartile-range 4.7-6.0), during which 63 patients developed AF. In a multivariable Cox regression model adjusted for relevant clinical and biochemical variables, MR-proANP was significantly associated with the development of AF (HR 1.18 per 100 pmol, 95% CI 1.11-1.28, p < 0.001). In a subgroup of patients who underwent echocardiography (N = 360), MR-proANP remained significantly associated with the development of AF (HR 1.39 per 100 pmol, 95% CI 1.13-1.71, p = 0.002) after adjusting for clinical and biochemical variables and left ventricular ejection fraction. When stratifying patients according to tertiles of MR-proANP, patients in the upper tertile displayed an 11 times greater risk of developing AF during follow-up as compared to patients in the lower tertile (HR 11.1, 95% CI 4.4-28.2, p < 0.001). Plasma MR-proANP measured at admission is an independent predictor of incident AF after STEMI.

Topics: Atrial Fibrillation; Atrial Natriuretic Factor; Biomarkers; Humans; ST Elevation Myocardial Infarction; Stroke Volume; Ventricular Function, Left

Atrial natriuretic peptide (ANP) is secreted in response to the stretching of the atrial wall. Atrial ischemia most likely impairs the ability of atrial myocytes to produce ANP. Atrial infarction (AI) is rarely diagnosed but not infrequently associated with myocardial infarction (MI). The aim of the study was to assess the association between AI and the prognostic value of N-terminal proANP (NT-proANP) in patients with MI treated with primary percutaneous coronary intervention (PCI). We evaluated data of 100 consecutive patients. Plasma levels of NT-proANP were measured by the ELISA method. ECG recordings were interpreted to diagnose AI according to Liu's criteria. All patients were followed-up prospectively for 12 months for the manifestation of major adverse cardiovascular events (MACE), defined as unplanned coronary revascularization, stroke, reinfarction or all-cause death. AI was diagnosed in 36 patients. 14% of patients developed MACE. AI did not affect the incidence of MACE or any of its components, nor the patients' prognosis. NT-proANP revealed to be a strong predictor of death but was not associated with other adverse events. Conclusions: AI in patients with MI treated with primary PCI is not connected with their prognosis nor affects the usefulness of NT-proANP in predicting death during the 12-month follow-up.

Topics: Aged; Atrial Natriuretic Factor; Biomarkers; Electrocardiography; Female; Heart Atria; Humans; Male; Middle Aged; Percutaneous Coronary Intervention; Prognosis; Prospective Studies; Protein Precursors; ST Elevation Myocardial Infarction

Cardiogenic shock complicating ST-elevation myocardial infarction is characterised by progressive left ventricular dysfunction causing inflammation and neurohormonal activation. Often, cardiogenic shock develops after hospital admission. Whether inflammation and a neurohormonal activation precede development of clinical cardiogenic shock is unknown.. Pro-atrial natriuretic peptide, copeptin, mid-regional pro-adrenomedullin and stimulation-2 admission plasma concentration were associated with late cardiogenic shock development in patients admitted with suspected ST-elevation myocardial infarction. Pro-atrial natriuretic peptide, mid-regional pro-adrenomedullin and copeptin had independent predictive value for late cardiogenic shock development.

Topics: Aged; Atrial Natriuretic Factor; Biomarkers; Female; Follow-Up Studies; Humans; Male; Natriuretic Peptide, Brain; Prognosis; Retrospective Studies; ROC Curve; Shock, Cardiogenic; ST Elevation Myocardial Infarction

Several biomarkers have individually been shown to be useful for risk stratification in patients with acute myocardial infarction (MI). The optimal multimarker strategy remains undefined.. Biomarkers representing different pathobiological axes were studied, including myocardial stress/structural changes (NT-pro B-type natriuretic peptide [NT-proBNP], midregional proatrial natriuretic peptide [MR-proANP], suppression of tumorigenicity 2 [ST2], galectin-3, midregional proadrenomedullin [MR-proADM], and copeptin), myonecrosis (troponin T), and inflammation (myeloperoxidase [MPO], high sensitivity C-reactive protein [hsCRP], pregnancy-associated plasma protein A [PAPP-A], and growth-differentiation factor-15 [GDF-15]), in up to 1258 patients from Clopidogrel as Adjunctive Reperfusion Therapy-Thrombolysis in Myocardial Infarction 28 (CLARITY-TIMI 28), a randomized trial of clopidogrel in ST-elevation MI (STEMI). Patients were followed for 30 days. Biomarker analyses were adjusted for traditional clinical variables. Forward step-wise selection was used to assess a multimarker strategy. After adjustment for clinical variables and using a dichotomous cutpoint, 7 biomarkers were each significantly associated with a higher odds of cardiovascular death or heart failure (HF) through 30 days, including NT-proBNP (adjusted odds ratio [ORadj], 2.54; 95% CI, 1.47-4.37), MR-proANP (2.18; 1.27-3.76), ST2 (2.88; 1.72-4.81), troponin T (4.13; 1.85-9.20), MPO (2.75; 1.20-6.27), hsCRP (1.96, 1.17-3.30), and PAPP-A (3.04; 1.17-7.88). In a multimarker model, 3 biomarkers emerged as significant and complementary predictors of cardiovascular death or HF: ST2 (ORadj, 2.87; 1.61-5.12), troponin T (2.34; 1.09-5.01 and 4.13, 1.85-9.20, respectively for intermediate and high levels), and MPO (2.49; 1.04-5.96). When added to the TIMI STEMI Risk Score alone, the multimarker risk score significantly improved the C-statistic (area under the curve, 0.75 [95% CI, 0.69-0.81] to 0.82 [0.78-0.87]; P=0.001), net reclassification index (0.93; P<0.001), and integrated discrimination index (0.09; P<0.001).. In patients with STEMI, a multimarker strategy that combines biomarkers across pathobiological axes of myocardial stress, myocyte necrosis, and inflammation provides incremental prognostic information for prediction of cardiovascular death or HF.

Topics: Adrenomedullin; Aged; Atrial Natriuretic Factor; Biomarkers; Blood Proteins; C-Reactive Protein; Cardiovascular Diseases; Female; Galectin 3; Galectins; Glycopeptides; Growth Differentiation Factor 15; Heart Failure; Humans; Interleukin-1 Receptor-Like 1 Protein; Male; Middle Aged; Natriuretic Peptide, Brain; Odds Ratio; Peptide Fragments; Peroxidase; Pregnancy-Associated Plasma Protein-A; Prognosis; Protein Precursors; Risk Assessment; ST Elevation Myocardial Infarction; Troponin T