Martin Reindl

Relation of inflammatory markers with myocardial and microvascular injury in patients with reperfused ST-elevation myocardial infarction

Background: In patients with acute ST-elevation myocardial infarction (STEMI), elevated concentrations of inflammatory markers are correlated with worse clinical outcome. The aim of this study was comprehensively to investigate the relationship of circulating markers of inflammation with myocardial and microvascular damage after STEMI. Methods: In 111 consecutive STEMI patients, blood samples were obtained on admission and from day 1 to day 4 after primary percutaneous coronary intervention and analysed for high-sensitivity C-reactive protein (hs-CRP), white blood cell count and fibrinogen. Cardiac magnetic resonance imaging was performed within the first week and 4 months after primary percutaneous coronary intervention. Results: Peak concentrations of hs-CRP (20.5 (9.6–44.4) mg/L), white blood cell count (12.4 (10.5–15.3) G/L) and fibrinogen (3640 (3150–4550) mg/L) showed significant correlations with both infarct size (r=0.31 to 0.41; P<0.01) and left ventricular ejection fraction (r=−0.29 to −0.39; P<0.01) assessed in the acute as well as chronic stage following STEMI. Furthermore, peak concentrations of these inflammatory markers were significantly higher in patients with microvascular obstruction compared to patients without microvascular obstruction (P⩽0.01). C-statistics revealed that the prognostic values of all three biomarkers for the prediction of large chronic infarct size (>8% of left ventricular myocardial mass) were moderate without significant differences (area under the curve: hs-CRP 0.73 (95% confidence interval (CI) 0.63–0.82), white blood cell count 0.67 (95% CI 0.56–0.78) and fibrinogen 0.69 (95% CI 0.59–0.79); all P>0.12). Combination of inflammatory markers did not significantly increase the area under the curve (P>0.05). Conclusion: In reperfused STEMI patients, increased levels of hs-CRP, white blood cell count and fibrinogen are associated with decreased left ventricular function and more pronounced myocardial damage at baseline and 4 months after infarction.

Fibroblast growth factor 23 as novel biomarker for early risk stratification after ST-elevation myocardial infarction

Objective Adverse left ventricular (LV) remodelling is the major determinant of heart failure and mortality in survivors of ST-elevation myocardial infarction (STEMI). The role of fibroblast growth factor 23 (FGF-23) for LV remodelling prediction after STEMI is unknown. We therefore aimed to investigate the relation between circulating FGF-23 and LV remodelling following revascularised STEMI. Methods In this prospective observational study, we included 88 consecutive patients with STEMI treated by primary percutaneous coronary intervention. FGF-23 concentrations were measured 2 (IQR: 2–2) days after symptom onset. Cardiac magnetic resonance was performed 2 (IQR: 1–3) days as well as 4 (IQR: 4–5) months after infarction to evaluate LV remodelling, defined as ≥20% increase in LV end-diastolic volume. Results Levels of FGF-23 were significantly higher in patients who developed LV remodelling (n=11, 13%) as compared with those without LV remodelling (152.6 (102.5–241.3) vs 75.8 (58.6–105.4) relative units per millilitre, p=0.002). The association between FGF-23 and LV remodelling remained significant (OR: 14.1, 95% CI 2.8 to 70.9; p=0.001) after adjustment for biomarkers reflecting myocardial necrosis (high-sensitivity cardiac troponin T (hs-cTnT)), myocardial stress (N-terminal pro B-type natriuretic peptide (NT-proBNP)) and inflammatory state (high-sensitivity C reactive protein (hs-CRP)). Moreover, a multimarker approach adding FGF-23 to the established LV remodelling-predictive biomarkers (hs-cTnT, NT-proBNP and hs-CRP) led to a net reclassification improvement of 0.92 (95% CI 0.44 to 1.41, p<0.001) and to an integrated discrimination improvement of 0.16 (95% CI 0.08 to 0.24, p<0.001). Conclusions Circulating FGF-23 is independently associated with LV remodelling after reperfused STEMI. A comprehensive multimarker strategy that includes FGF-23 provides incremental prognostic value for prediction of LV remodelling.

N-Chlorotaurine Exhibits Fungicidal Activity against Therapy-Refractory Scedosporium Species and Lomentospora prolificans

ABSTRACT N-Chlorotaurine (NCT), a well-tolerated endogenous long-lived oxidant that can be applied topically as an antiseptic, was tested on its fungicidal activity against Scedosporium and Lomentospora, opportunistic fungi that cause severe infections with limited treatment options, mainly in immunocompromised patients. In quantitative killing assays, both hyphae and conidia of Scedosporium apiospermum, Scedosporium boydii, and Lomentospora prolificans (formerly Scedosporium prolificans) were killed by 55 mM (1.0%) NCT at pH 7.1 and 37°C, with a 1- to 4-log10 reduction in CFU after 4 h and a 4- to >6-log10 reduction after 24 h. The addition of ammonium chloride to NCT markedly increased this activity. LIVE/DEAD staining of conidia treated with 1.0% NCT for 0.5 to 3 h increased the permeability of the cell wall and membrane. Preincubation of the test fungi in 1.0% NCT for 10 to 60 min delayed the time to germination of conidia by 2 h to >12 h and reduced their germination rate by 10.0 to 100.0%. Larvae of Galleria mellonella infected with 1.0 × 107 conidia of S. apiospermum and S. boydii died at a rate of 90.0 to 100% after 8 to 12 days. The mortality rate was reduced to 20 to 50.0% if conidia were preincubated in 1.0% NCT for 0.5 h or if heat-inactivated conidia were used. Our study demonstrates the fungicidal activity of NCT against different Scedosporium and Lomentospora species. A postantifungal effect connected with a loss of virulence occurs after sublethal incubation times. The augmenting effect of ammonium chloride can be explained by the formation of monochloramine.

Oscillometric analysis compared with cardiac magnetic resonance for the assessment of aortic pulse wave velocity in patients with myocardial infarction.

Objectives: Measurement of aortic pulse wave velocity (PWV) is the gold standard for assessment of aortic stiffness. In patients with ST-segment elevation myocardial infarction (STEMI), high aortic PWV has deleterious effects on the myocardium. In the present study, we compared a novel oscillometric device with cardiac magnetic resonance (CMR) imaging for the assessment of aortic PWV in STEMI patients. Methods: We measured aortic PWV in 60 reperfused STEMI patients using two different methods. The oscillometric method (PWVOSC) is based on mathematical transformation of brachial pressure waveforms, oscillometrically determined using a common cuff (Mobil-O-Graph, I.E.M., Stolberg, North Rhine-Westphalia, Germany). Phase-contrast CMR imaging (1.5 T scanner, Siemens, Erlangen, Bavaria, Germany) at the level of the ascending and abdominal aorta was performed to determine CMR-derived pulse wave velocity with the use of the transit time method. Results: The mean age of the study population was 57 ± 11 years; 11 (18%) were women. Median PWVOSC was 7.4 m/s (interquartile range 6.8–8.9 m/s), and median CMR-derived pulse wave velocity was 6.3 m/s (interquartile range 5.7–8.2 m/s) (P < 0.001). A strong correlation was detected between both methods (r = 0.724, P < 0.001). Bland–Altman analysis revealed a bias of 0.62 m/s (upper and lower limit of agreement: 3.84 and −2.61 m/s). The coefficient of variation between both methods was 21%. Conclusion: In reperfused STEMI patients, aortic PWV assessed noninvasively by transformation of brachial pressure waveforms showed an acceptable agreement with the CMR-derived transit time method.

Heart rate and left ventricular adverse remodelling after ST-elevation myocardial infarction

BACKGROUND Discharge heart rate (HR) following ST-elevation myocardial infarction (STEMI) is a predictor of adverse left ventricular remodelling (LVR). However, the prognostic relevance of HR values in the earlier phase after revascularization is unknown. We aimed to investigate resting HR assessed at different time points during hospital stay following STEMI for the prediction of LVR. METHODS In this prospective observational study of 143 consecutive STEMI patients, HR was measured serially on admission (AHR), at day 1 (HRd1) and 2 (HRd2) following revascularization and finally at discharge (DHR). Cardiac magnetic resonance (CMR) scans were performed at baseline and 4months thereafter to evaluate LVR and major CMR determinants of LVR (infarct size, microvascular obstruction). LVR was defined as ≥15% increase of left ventricular end-diastolic volume. RESULTS Twenty-nine patients (20%) have developed LVR. HRd1 (80[72-88] vs. 71[62-79]bpm, p=0.003), HRd2 (74[64-83] vs. 67[59-78]bpm, p=0.04), DHR (74[62-81] vs. 64[58-73] bpm, p=0.008) and the mean HR of all measurements (76[68-82] vs. 67[60-77]bpm, p=0.004) were significantly higher in patients with LVR, whereas admission HR (75[68-85] vs. 70[60-82]bpm, p=0.12) did not differ significantly. The associations for all post-admission HRs remained significant after adjustment for clinical (high-sensitivity cardiac troponin T and C-reactive protein, left anterior descending artery as culprit) and CMR (infarct size, microvascular obstruction, ejection fraction) predictors of LVR. The predictive values of the post-admission HRs were equivalent (area under the curve differences: all p>0.05). CONCLUSION Besides DHR, resting HR values in the early stage following reperfusion are independent predictors of LVR after STEMI.

Prognostic significance of transaminases after acute ST-elevation myocardial infarction: insights from a cardiac magnetic resonance study.

SummaryBackgroundIn patients with ST-elevation myocardial infarction (STEMI), the relationship between transaminases and myocardial damage detected by cardiac magnetic resonance (CMR) imaging is unknown and the prognostic value incompletely investigated.Materials and methodsCMR imaging was performed in 167 STEMI patients 2.3 [1.6–3.9] days after primary percutaneous coronary intervention (PPCI). Blood samples for transaminase measurement (aspartate transaminase (AST) and alanine transaminase (ALT)) were obtained serially from day 1 to day 4 after PPCI. Patients were followed for major adverse cardiac events (MACE) for 2.7 [1.1–3.3] years.ResultsAdmission and peak concentrations of AST and ALT were significantly associated with ejection fraction (p < 0.001), infarct size (p < 0.001), and the presence of microvascular obstruction (p < 0.01). Peak values of both transaminases showed a stronger correlation with CMR parameters than admission values (all p < 0.05). In Kaplan–Meier analysis, a high peak AST or high peak ALT was associated with reduced MACE-free survival (both p < 0.01), whereas admission values were not (both p > 0.05). Peak AST (hazard ratio (HR): 4.93 [1.70–14.32], p = 0.003) and peak ALT (HR: 5.67 [1.94–16.56], p = 0.002) were independent predictors of MACE after adjusting for clinical risk factors.ConclusionsTransaminases measured in the acute phase after PPCI for STEMI are associated with systolic dysfunction, more extensive myocardial necrosis and microvascular injury with subsequent prognostic information on MACE at long-term follow-up.

Combined biomarker testing for the prediction of left ventricular remodelling in ST-elevation myocardial infarction

Objective The utility of different biomarkers for the prediction of left ventricular remodelling (LVR) following ST-elevation myocardial infarction (STEMI) has been evaluated in several studies. However, very few data exist on the prognostic value of combined biomarkers. The aim of this study was to comprehensively investigate the prognostic value for LVR of routinely available biomarkers measured after reperfused STEMI. Methods Serial measurements of N-terminal pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity cardiac troponin T (hs-cTnT), aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH) and high-sensitivity C reactive protein (hs-CRP) were performed in 123 patients with STEMI treated with primary percutaneous coronary intervention in this prospective observational study. Patients underwent cardiac MRI at 2 (1–4) and 125 (121–146) days after infarction. An increase in end-diastolic volume of ≥20% was defined as LVR. Results LVR occurred in 16 (13%) patients. Peak concentrations of the following biomarkers showed significant areas under the curves (AUCs) for the prediction of LVR—NT-proBNP: 0.68 (95% CI 0.59 to 0.76, p=0.03), hs-cTnT: 0.75 (95% CI 0.66 to 0.82, p<0.01), AST: 0.72 (95% CI 0.63 to 0.79, p<0.01), ALT: 0.66 (95% CI 0.57 to 0.75, p=0.03), LDH: 0.78 (95% CI 0.70 to 0.85, p<0.01) and hs-CRP: 0.63 (95% CI 0.54 to 0.72, p=0.05). The combination of all biomarkers yielded a significant increase in AUC to 0.85 (95% CI 0.77 to 0.91) (all vs NT-proBNP: p=0.02, all vs hs-cTnT: p=0.02, all vs AST: p<0.01, all vs ALT: p<0.01, all vs hs-CRP: p<0.01 and all vs LDH: p=0.04). Conclusions In patients with reperfused STEMI, the combined assessment of peak NT-proBNP, hs-cTnT, AST, ALT, hs-CRP and LDH provide incremental prognostic information for the prediction of LVR when compared with single-biomarker measurement.

Utility of NT-proBNP in predicting infarct scar and left ventricular dysfunction at a chronic stage after myocardial infarction

• Associations of natriuretic peptides and cardiac troponins with infarct scare at a chronic stage are proposed.

Multimarker approach for the prediction of microvascular obstruction after acute ST-segment elevation myocardial infarction: a prospective, observational study

BackgroundPresence of microvascular obstruction (MVO) derived from cardiac magnetic resonance (CMR) imaging is among the strongest outcome predictors after ST-segment elevation myocardial infarction (STEMI). We aimed to investigate the comparative predictive values of different biomarkers for the occurrence of MVO in a large cohort of reperfused STEMI patients.MethodsThis study included 128 STEMI patients. CMR imaging was performed within the first week after infarction to assess infarct characteristics, including MVO. Admission and peak concentrations of high-sensitivity cardiac troponin T (hs-cTnT), creatine kinase (CK), N-terminal pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity C-reactive protein (hs-CRP), lactate dehydrogenase (LDH), aspartate transaminase (AST) and alanine transaminase (ALT) were measured.ResultsMVO was detected in 69 patients (54%). hs-cTnT, CK, hs-CRP, LDH, AST and ALT peak concentrations showed similar prognostic value for the prediction of MVO (area under the curve (AUC) = 0.77, 0.77, 0.68, 0.79, 0.78 and 0.73, all p > 0.05), whereas the prognostic utility of NT-proBNP was weakly lower (AUC = 0.64, p < 0.05). Combination of these biomarkers did not increase predictive utility compared to hs-cTnT alone (p = 0.349).Conclusionshs-cTnT, CK, hs-CRP, LDH, AST and ALT peak concentrations provided similar prognostic value for the prediction of MVO. The prognostic utility of NT-proBNP was lower. Combining these biomarkers could not further improve predictive utility compared to hs-cTnT alone.

Acute kidney injury is associated with microvascular myocardial damage following myocardial infarction

Acute kidney injury (AKI) is a frequent complication in patients with ST-elevation myocardial infarction (STEMI) treated by primary percutaneous coronary intervention. However, the pathophysiology of AKI in this setting is complex and goes beyond the administration of contrast media. Studies assessing the impact of infarct characteristics on AKI are currently lacking. Therefore, we investigated the association of AKI with myocardial as well as microvascular injury in an initial total of 361 consecutive STEMI patients treated by primary percutaneous coronary intervention. Of these, 318 patients were included in final analysis. Serum creatinine was measured on admission as well as 24, 48, and 72 hours thereafter with AKI defined as an increase in serum creatinine of 0.3 mg/dl or more. Cardiac magnetic resonance (CMR) scans were performed in the first week after infarction, with microvascular injury visualized by late gadolinium enhancement CMR defined as any region of hypoenhancement within the hyperenhanced area of infarction. Sixteen patients developed AKI. They showed significantly lower left ventricular ejection fraction (45[interquartile range 40-52]% vs. 54[47-59]%), larger infarct size (21[15-35]% vs. 12[7-22]%) of left ventricular myocardial mass, and more frequent microvascular injury (81 vs. 46%) than those free of AKI. Meaningfully, in multivariate analysis including all CMR data, microvascular injury was the sole independent predictor of AKI (odds ratio 6.74, 95% confidence interval of 1.49-30.43). Thus, among revascularized STEMI patients, the presence of microvascular injury assessed by CMR was independently associated with an increased risk of AKI. This suggests a potential pathophysiological link between cardiac microvascular disease and renal injury following STEMI.