Luise Gaede

Release Kinetics of Circulating Muscle-Enriched MicroRNAs in Patients Undergoing Transcoronary Ablation of Septal Hypertrophy

OBJECTIVES This study sought to evaluate exact release kinetics of microRNAs (miRNAs) in acute myocardial infarction (AMI). BACKGROUND miRNAs may be useful as novel biomarkers in patients with cardiovascular disease, although it is difficult to establish the detailed release kinetics of miRNAs in patients with AMI. METHODS We analyzed the release kinetics of circulating cardiac-specific (miR-21, miR-208a) and muscle-enriched (miR-1, miR-133a) miRNAs using the TaqMan polymerase chain reaction in patients with hypertrophic obstructive cardiomyopathy who were undergoing transcoronary ablation of septal hypertrophy (TASH), a procedure mimicking AMI. Consecutive patients (n = 21) undergoing TASH were included. Serum samples were collected prior to and at 15, 30, 45, 60, 75, 90, and 105 min and 2, 4, 8, and 24 h after TASH. RESULTS Circulating concentrations of miR-1 were significantly increased (>3-fold; p = 0.01) after 15 min, with a peak after 75 min (>60-fold; p < 0.001). The miR-21 concentrations were not increased at any time point. Concentrations of miR-133a were significantly increased at 15 min (2.9-fold; p < 0.001) and reached a plateau between 75 and 480 min (>50-fold change). The miR-208a concentrations were elevated at 105 min (>2-fold; p = 0.01), without a further increase. CONCLUSIONS miR-1, miR-133a, and miR-208a were continuously increased during the first 4 h after the induction of MI. In particular, miR-1 and miR-133a were significantly increased at early time points. These results demonstrate the release kinetics of miRNAs, which are helpful for developing their potential use as biomarkers in patients with acute coronary syndromes.

Soluble fms-like tyrosine kinase-1 and endothelial adhesion molecules (intercellular cell adhesion molecule-1 and vascular cell adhesion molecule-1) as predictive markers for blood pressure reduction after renal sympathetic denervation.

Renal sympathetic denervation (RSD) is a treatment option for patients with resistant arterial hypertension, but in some patients it is not successful. Predictive parameters on the success of RSD remain unknown. The angiogenic factors soluble fms-like tyrosine kinase-1 (sFLT-1), intercellular cell adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) are known to be associated with endothelial dysfunction, vascular remodeling, and hypertension. We evaluated whether sFLT-1, ICAM-1, and VCAM-1 are predictive markers for blood pressure reduction after RSD. Consecutive patients (n=55) undergoing renal denervation were included. Venous serum samples for measurement of sFlt-1, ICAM-1, and VCAM-1 were collected before and 6 months after RSD. A therapeutic response was defined as an office systolic blood pressure reduction of >10 mm Hg 6 months after RSD. A significant mean office systolic blood pressure reduction of 31.2 mm Hg was observed in 46 patients 6 months after RSD. Nine patients were classified as nonresponders, with a mean systolic blood pressure reduction of 4.6 mm Hg. At baseline, sFLT-1 levels were significantly higher in responders than in nonresponders (P<0.001) as were ICAM-1 (P<0.001) and VCAM-1 levels (P<0.01). The areas under the curve for sFLT-1, ICAM-1, and VCAM-1 were 0.82 (interquartile range, 0.718–0.921; P<0.001), 0.754 (0.654–0.854; P<0.001), and 0.684 (0.564–804; P=0.01), respectively, demonstrating prediction of an RSD response. Responders showed significantly higher serum levels of sFLT-1, ICAM-1, and VCAM-1 at baseline compared with nonresponders. Thus, this study identified for the first time potential biomarkers with a predictive value indicating a responder or nonresponder before renal denervation.

Extracorporeal life support in cardiovascular patients with observed refractory in-hospital cardiac arrest is associated with favourable short and long-term outcomes: A propensity-matched analysis.

Aims: Extracorporeal life support (ECLS) has shown encouraging survival rates in patients with in-hospital cardiac arrest; however, its routine use is still controversial. We compared the survival of patients with in-hospital cardiac arrest receiving conventional cardiopulmonary resuscitation (CCPR) to that of patients with ECLS as an adjunct to cardiopulmonary resuscitation (ECPR). Methods: A total of 353 patients with in-hospital cardiac arrest (272 CCPR and 52 ECPR) were included in this retrospective, propensity score-adjusted (1:1 matched), single-centre study. Primary endpoints were survival at 30 days, long-term survival and neurological outcome defined by the cerebral performance categories score. Results: In the unmatched groups patients undergoing ECPR initially had significantly higher APACHE II scores (P=0.03), increased norepinephrine dosages (P=0.03) and elevated levels of creatine kinase (P<0.0001), creatinine (P=0.04) and lactate (P=0.02) before cardiopulmonary resuscitation compared with those undergoing CCPR. After equalising these parameters significant differences were observed in short and long-term survival, favouring ECPR over CCPR (27% vs. 17%; P=0.01 (short-term) and 23.1% vs. 11.5%; P=0.008 (long-term); median follow-up duration after discharge 1136 days (interquartile range 823–1416)). There was no significant difference in the incidence of a cerebral performance categories score of 1 or 2 between the matched groups (CCPR 66.7% vs. ECPR 83.3%; P=0.77). ECLS implantation was the only significant and independent predictor of mortality in multivariate Cox regression analysis (hazard ratio 0.57, 95% confidence interval 0.35–0.90; P=0.02). Conclusion: In our cohort of cardiovascular patients ECPR was associated with better short- and long-term survival over CCPR, with a good neurological outcome in the majority of the patients with refractory in-hospital cardiac arrest.

Neutrophil gelatinase-associated lipocalin (NGAL) for the early detection of cardiac surgery associated acute kidney injury

Abstract Background. Acute kidney injury (AKI) is a common complication after cardiac surgery. Neutrophil gelatinase-associated lipocalin (NGAL) may be an early biomarker for cardiac surgery–associated (CSA) AKI. We investigated whether increased urinary NGAL concentrations were predictive of AKI within 4 days after surgery and of mortality within 9 months. Methods. Consecutive patients (n = 141) undergoing major cardiac surgery were included. Creatinine, blood urea nitrogen, cystatin C and urinary NGAL were measured before, 4 hours and 4 days after extracorporeal circulation. Results. AKI was observed in 47 (33.3%) patients. The 4-hour urinary NGAL measurement was an independent predictor of stage 2 and 3 AKI (AUC 0.901; 95% CI 0.81–0.99). Patients with AKI had a higher 9-month mortality rate (19.1% vs. 3.2%; logrank 10.9; P = 0.001; HR 19.8; 95% CI 3.7–107.1). Urinary NGAL was not predictive of mortality within 9 months after surgery. Conclusion. Urinary NGAL is a biomarker for very early risk stratification of AKI after cardiac surgery and may be useful as a basis for early interventional strategies to prevent CSA-AKI.

Trends in aortic valve replacement in Germany in 2015: transcatheter versus isolated surgical aortic valve repair

AimsWe analysed the number of procedures, indications, and in-hospital mortality rates of all patients undergoing isolated surgical aortic valve replacement (sAVR) or transvascular (TV-) and transapical (TA-) transcatheter aortic valve implantation (TAVI) from 2012 to 2015 in Germany.Methods and resultsMore than 31,000 aortic valve procedures were performed in 2015 in Germany, representing a total increase of 4.5% over 2014. TV-TAVI accounts for 13,108 of these procedures, with an increase of 21%, whereas the numbers of isolated sAVR and TA-TAVI decreased slightly. Age, frailty, high risk, and patients’ choice were the main reasons for a catheter-based intervention. In 2015, the in-hospital mortality rate after TV-TAVI decreased to 3.4%, approaching that of sAVR (2.9%), despite a considerably higher baseline risk. A stratified analysis according to the German aortic valve (AKL) score demonstrated a further decrease of the in-hospital mortality for TV-TAVI, showing a lower in-hospital mortality rate than expected in all risk groups. Importantly, this also accounts for the lowest risk group with an AKL score <3% showing an in-hospital mortality rate of 1.7%, which is now comparable to that of sAVR (1.5%). In all other risk groups, the in-hospital mortality in patients undergoing TV-TAVI was lower than in patients undergoing sAVR.ConclusionsMortality after TV-TAVI keeps decreasing over the last years and equals that of SAVR in the lowest risk cohort in the meanwhile. All TV-TAVI patients have significantly lower observed than expected mortality, which will further lead to a redefinition of standard of care.

Release Kinetics of Inflammatory Biomarkers in a Clinical Model of Acute Myocardial Infarction

RATIONALE Inflammation in the setting of acute myocardial infarction (MI) has been linked to risk stratification; however, the release kinetics of inflammatory biomarkers in patients with acute MI has been difficult to establish. OBJECTIVE The aim of this study was to determine the kinetics of changes in the levels of several biomarkers specifically linked to inflammation after transcoronary ablation of septal hypertrophy, a procedure that mimics acute MI. METHODS AND RESULTS We analyzed release kinetics of C-reactive protein, high-sensitivity C-reactive protein, interleukin-6, soluble CD40 ligand, and peripheral blood leukocyte subsets in patients (n=21) undergoing transcoronary ablation of septal hypertrophy. Blood samples were collected before transcoronary ablation of septal hypertrophy and at various times after transcoronary ablation of septal hypertrophy. Serum levels of C-reactive protein were increased at 24 hours (1.0 mg/dL [interquartile range [IQR], 0.7-1.75] versus 0.2 mg/dL [IQR, 0.1-1.05] at baseline [BL]; P<0.001), whereas high-sensitivity C-reactive protein increased as early as 8 hours (2.68 mg/L [IQR, 1.23-11.80] versus 2.17 mg/L [IQR, 1.15-5.06] at BL; P=0.002). Interleukin-6 was significantly increased at 45 minutes (2.59 pg/mL [IQR, 1.69-5.0] versus 1.5 pg/mL [IQR, 1.5-2.21] at BL; P=0.002), and soluble CD40 ligand was significantly decreased at 60 minutes (801.6 pg/mL [IQR, 675.0-1653.5] versus 1750.0 pg/mL [IQR, 1151.0-2783.0] at BL; P=0.016). Elevated counts of polymorphonuclear neutrophils were detectable at 15 minutes, with a significant increase at 2 hours (6415 cells/μL [IQR, 5288-7827] versus 4697 cells/μL [IQR, 2892-5620] at BL; P=0.004). Significant monocytosis was observed at 24 hours (729 cells/μL [IQR, 584-1344] versus 523 cells/μL [IQR, 369-701] at BL; P=0.015). CONCLUSIONS Interleukin-6 and neutrophil granulocytes showed a continuous rise at all prespecified time points after induction of MI. Our results provide valuable additional evidence of the diagnostic value of inflammatory biomarkers in the setting of early acute MI.

Release kinetics of early ischaemic biomarkers in a clinical model of acute myocardial infarction

Objective To determine the release kinetics of different biomarkers with potential as novel early ischaemic biomarkers in patients with acute coronary syndrome (ACS); it is difficult to establish the detailed release kinetics in patients with acute myocardial infarction (AMI). Methods We analysed the release kinetics of soluble fms-like tyrosine kinase (sFlt-1), ischaemia modified albumin (IMA), and heart-type fatty acid binding protein (hFABP) in patients with hypertrophic obstructive cardiomyopathy who were undergoing transcoronary ablation of septal hypertrophy (TASH), a procedure mimicking AMI. Consecutive patients (n=21) undergoing TASH were included. Blood samples were collected before TASH and 15, 30, 45, 60, 75, 90, and 105 min and 2, 4, 8, and 24 h after TASH. sFlt-1 and hFABP were quantified in serum, and IMA was quantified in plasma using immunoassays. Results sFLT-1 and hFABP increased significantly 15 min after induction of AMI vs baseline as follows: sFlt-1, 3657.5 ng/L (IQR 2302.3–4475.0) vs 76.0 ng/L (IQR 71.2–88.8) (p<0.001); hFABP, 9.0 ng/mL (IQR 7.0–15.4) vs 4.6 ng/mL (IQR 3.4–7.1) (p<0.001). sFlt-1 demonstrated a continuous decrease after the 15th min. hFABP showed a continuous increase until the 8th hour with a decline afterwards. The IMA concentrations increased significantly 30 min after induction of AMI vs baseline, with values of 26.0 U/mL (IQR 21.8–38.6) vs 15.6 U/mL (IQR 10.1–24.7) (p=0.02), and then decreased after 75 min. Conclusions sFlt-1 and hFABP increased very early after induction of myocardial ischaemia, showing different release kinetics. The additional information provided by these findings is helpful for developing their potential combined use with cardiac troponins in patients with suspected AMI.

Transfemoral aortic valve implantation of Edwards SAPIEN 3 without predilatation

The purpose of the present study was to investigate whether transfemoral implantation of the balloon‐expandable Edwards SAPIEN 3 device without prior balloon valvuloplasty is feasible.

Neutrophil gelatinase-associated lipocalin (NGAL) for the early detection of contrast-induced nephropathy after percutaneous coronary intervention

Abstract Background. Contrast-induced acute kidney injury (CI-AKI) occurs in up to 13% of patients undergoing percutaneous coronary intervention (PCI). Neutrophil gelatinase-associated lipocalin (NGAL) is an early biomarker for renal impairment. We investigated whether increased urinary NGAL concentrations were predictive of CI-AKI within 2 days after PCI or of a higher re-hospitalization rate within 9 months. Methods. Consecutive patients (n = 128), with stable coronary heart disease and eGFR ≥ 30 mL/min/1.73 m2, undergoing PCI were included. Venous serum samples for measurement of creatinine, blood urea nitrogen, and cystatin C and urine samples for NGAL measurement were collected 4 hours and 1 and 2 days after contrast medium application. Patients were followed over 9 months to determine clinical endpoints. Results. CI-AKI was observed in 14 patients (10.9%) after PCI. NGAL concentrations before PCI were significantly higher in patients with subsequent CI-AKI (19.8 ng/mL [14.4–35.8] vs. 11.6 ng/mL [5.6–28.2]; p = 0.04). There was no significant difference in NGAL concentrations 4 h after PCI between patients with and without CI-AKI. One day after PCI, NGAL concentrations were significant higher in patients developing CI-AKI (100.1 ng/mL [41.5–129.2] vs. 16.6 ng/mL [9.1–28.1]; p < 0.001). Compared to common biomarkers, NGAL best predicted CI-AKI (AUC 0.939 [95% CI 0.89–0.99; p < 0.001]). The re-hospitalization rate due to progressive renal insufficiency within 9 months was higher in the group with CI-AKI than the group without (4 [28.6%] vs. 4 [3.5%], p < 0.01). Conclusion. Urinary NGAL is a biomarker for predicting CI-AKI when measured 1 day after PCI.

Myocardial injury associated with transcatheter aortic valve implantation (TAVI)

Transcatheter aortic valve implantation (TAVI) has emerged as an important treatment option for elderly patients with symptomatic aortic stenosis whose risk is too high or prohibitive for conventional surgery. Despite notable progress during the past decade, continuous efforts directed at further improvement of procedural safety and performance are required, especially considering expanding indications for interventional treatment options among lower-risk populations. One issue that needs to be addressed is myocardial damage, which can frequently be observed after TAVI and has been linked to worse prognosis. Yet, knowledge concerning the underlying mechanisms and clinical impact remains scarce, and further investigation in this field is warranted. In this review, we provide a contemporary summary of the types of myocardial injury associated with TAVI, including access-related injury, mechanical trauma and ischemia, the role of myocardial biomarkers, and the impact on left ventricular function, with emphasis on potential mechanisms and clinical implications.