Johannes Rixe

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

OBJECTIVESnThis study sought to evaluate exact release kinetics of microRNAs (miRNAs) in acute myocardial infarction (AMI).nnnBACKGROUNDnmiRNAs 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.nnnMETHODSnWe 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.nnnRESULTSnCirculating 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.nnnCONCLUSIONSnmiR-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.

Preprocedural coronary CT angiography significantly improves success rates of PCI for chronic total occlusion

AbstractnChronic total occlusions of coronary arteries occur in about 20xa0% of patients with suspected coronary artery disease and are more frequent with increasing age. The success rate of interventions is lower (55–80xa0%) compared to conventional lesions (>90xa0%). Coronary CT angiography (coronary CTA) provides information about the occluded segment, which cannot be obtained from invasive angiograms (XA). We therefore hypothesized that preprocedural coronary CTA may improve success rates of percutaneous coronary intervention (PCI) for coronary arteries (CTO). 30 patients with chronic total coronary artery occlusions (mean age 73xa0years, 26 men) and predicted high complexity were imaged by coronary CTA prior to PCI for CTO. CT data sets were acquired with a 64 detector row dual source scanner and retrograde ECG gating, 0.6xa0mm collimation and z-flying focal spot, yielding isovoxel spatial resolution of about 0.4xa0mm. Based on the CT data sets, established complexity criteria for CTO (Euro CTO club, Di Mario et al. in EuroIntervention 3(1):30–43, 2007) were evaluated and compared to invasive coronary angiography. Three-dimensional volume-rendered images of the occluded coronary artery were displayed in the catheterization lab during PCI to guide the advancement of the wire. PCI success, defined as the ability to advance the guide wire into the distal lumen with thrombolysis in myocardial infarction III flow was compared to 43 controls without coronary CTA using propensity score matching based on established criteria of procedural success. The course of the occluded segments was visualized by coronary CTA in all cases. Calcification, lesion length, stump morphology and presence of side branches were underestimated by invasive angiograms when compared to coronary CTA. PCI success rate in 30 patients who underwent pre-procedural CTA was significantly higher than in patients without prior coronary CTA [unmatched: CT 90xa0% (27/30) vs. no CT 63xa0% (27/43), pxa0=xa00.009; matched: CT 88xa0% (22/25) vs. no CT 64xa0% (16/25) pxa0=xa00.03]. Through information not readily seen on invasive coronary angiography, coronary CTA can significantly enhance success rates of PCI for CTO.

Coronary Computed Tomographic Prediction Rule for Time-Efficient Guidewire Crossing Through Chronic Total Occlusion : Insights From the CT-RECTOR Multicenter Registry (Computed Tomography Registry of Chronic Total Occlusion Revascularization)

OBJECTIVESnThis study sought to establish a coronary computed tomography angiography prediction rule for grading chronic total occlusion (CTO) difficulty for percutaneous coronary intervention (PCI).nnnBACKGROUNDnThe uncertainty of procedural outcome remains the strongest barrier to PCI in CTO.nnnMETHODSnData from 4 centers involving 240 consecutive CTO lesions with pre-procedural coronary computed tomography angiography were analyzed. Successful guidewire (GW) crossing ≤30 min was set as an endpoint to eliminate operator bias. The CT-RECTOR (Computed Tomography Registry of Chronic Total Occlusion Revascularization) score was developed by assigning 1 point for each independent predictor, and then summing all points accrued. Continuous distribution of scores was used to stratify CTO into 4 difficulty groups: easy (score 0); intermediate (score 1); difficult (score 2); and very difficult (score ≥3). Discriminatory performance was tested by 10-fold cross-validation and compared with the angiographic J-CTO (Multicenter CTO Registry of Japan) score.nnnRESULTSnStudy endpoint was achieved in 55% of cases. Multivariable analysis yielded multiple occlusions, blunt stump, severe calcification, bending, duration of CTO ≥12 months, and previously failed PCI as independent predictors for GW crossing. The probability of successful GW crossing ≤30 min for each group (from easy to very difficult) was 95%, 88%, 57%, and 22%, respectively. Areas under receiver-operator characteristic curves for the CT-RECTOR and J-CTO scores were 0.83 and 0.71, respectively (p < 0.001). Both the original model fit and 10-fold cross-validation correctly classified 77.3% of lesions.nnnCONCLUSIONSnThe CT-RECTOR score represents a simple and accurate noninvasive tool for predicting time-efficient GW crossing that may aid in grading CTO difficulty before PCI. (Computed Tomography Angiography Prediction Score for Percutaneous Revascularization for Chronic Total Occlusions [CT-RECTOR]; NCT02022878).

Short-term outcome of patients with ST-segment elevation myocardial infarction (STEMI) treated with an everolimus-eluting bioresorbable vascular scaffold

AbstractObjectivesnTo evaluate safety and efficacy of the everolimus-eluting bioresorbable scaffold (BVS) in patients with ST-segment elevation myocardial infarction (STEMI).BackgroundAccording to the current guidelines, drug-eluting stents are the treatment of choice in patients with STEMI. BVS represents a new technology capable to restore the native vessel vasomotion and potentially avoiding long-term limitations such as stent thrombosis.MethodsFrom October 2012 to May 2013, patients with evidence of STEMI eligible for BVS implantation were included in this study. Exclusion criteria were not defined.ResultsA total of 25 patients, respectively 31 lesions, were treated. Procedural success was achieved in 97xa0%. Two major adverse cardiac events occurred during hospitalization and follow-up: one patient with cardiogenic shock at the index procedure subsequently died. One patient suffered from instable angina with need for interventional revascularization of a previously untreated vessel. One target vessel failure as a consequence of an intra-procedural dissection was seen. However, no target lesion failure was noted. During 132.7xa0±xa068.7xa0days of follow-up none of the patients died.ConclusionOur findings suggest that implantation of BVS in STEMI patients is feasible in this small cohort of highly selected patients. Further evaluation in randomized-controlled trials is needed.

Influence of heart rate and phase of the cardiac cycle on the occurrence of motion artifact in dual-source CT angiography of the coronary arteries

BACKGROUNDnCoronary CT angiography allows visualization of the coronary arteries. However, motion artifact can impair delineation of the coronary artery lumen and detection of coronary artery stenoses.nnnOBJECTIVEnWe investigated the influence of heart rate and the segment of the cardiac cycle during which images are reconstructed on the occurrence of motion artifacts.nnnMETHODSnWe evaluated coronary CT angiography datasets obtained by 64-slice dual-source CT in 100 consecutive patients. Data were reconstructed at 13 time instants during the cardiac cycle and evaluated for the presence of motion artifact.nnnRESULTSnMean heart rate was 66±14 beats/min. Overall, 98 of 100 patients had evaluable datasets. For heart rates ≤60 beats/min, optimal image quality was uniformly found during late diastole (100% of cases with evaluable image quality during a time window between 65% and 75% of the cardiac cycle). With increasing heart rates, images reconstructed during late systole more frequently provided best image quality. However, image reconstruction could not be restricted to a systolic time period. To achieve evaluable image quality in 95% of cases, data acquired between 25% and 75% of the cardiac cycle had to be available for patients with heart rates >60 beats/min.nnnCONCLUSIONnDual-source CT provides high image quality across a wide range of heart rates. Although data acquisition may be limited to diastole for patients with heart rates ≤60 beats/min, the availability of data acquired both during systole and diastole is necessary for patients with higher heart rates.

Release Kinetics of Copeptin in Patients Undergoing Transcoronary Ablation of Septal Hypertrophy

BACKGROUNDnThe release kinetics of copeptin in patients with acute myocardial infarction (AMI) have been difficult to establish.nnnMETHODSnWe analyzed the release kinetics of copeptin in patients with hypertrophic obstructive cardiomyopathy undergoing transcoronary ablation of septal hypertrophy (TASH) as a model of AMI. We included 21 consecutive patients who underwent TASH. Blood samples were collected before and at 15, 30, 45, 60, 75, 90, and 105 min, and at 2, 4, 8, and 24 h after TASH. Serum copeptin was quantified by a sandwich immunoluminometric assay.nnnRESULTSnAll patients had copeptin concentrations below the 99th percentile at baseline. The median copeptin concentration was significantly increased at 30 min [16.0 pmol/L; interquartile range (IQR), 13.4-20.2 pmol/L], compared with the median baseline concentration (6.6 pmol/L; IQR, 5.3-8.3 pmol/L; P = 0.002). The copeptin concentration peaked 90 min after induction of myocardial infarction and returned to baseline concentrations (median, 8.2 pmol/L; IQR, 6.3-10.1) after 24 h, compared with the above baseline values (P = 0.06). Serum creatine kinase (CK) activities were significantly increased above baseline values by 1 day after TASH [median maximal postprocedural CK activity, 935.0 U/L (IQR, 545.5-1115.0 U/L); median baseline CK activity, 80.0 U/L (IQR, 63.5-109.0 U/L); P < 0.001].nnnCONCLUSIONSnOur results provide additional evidence that early rule-out of suspected AMI is possible by using the copeptin concentration in combination with cardiac troponin T.

Regression of cardiac hypertrophy by granulocyte colony-stimulating factor-stimulated interleukin-1β synthesis

AIMSnAortic stenosis causes cardiac hypertrophy and fibrosis, which often persists despite pressure unloading after aortic valve replacement. The persistence of myocardial fibrosis in particular leads to impaired cardiac function and increased mortality. We investigated whether granulocyte colony-stimulating factor (G-CSF) beneficially influences cardiac remodelling after pressure unloading.nnnMETHODS AND RESULTSnLeft ventricular hypertrophy was induced by transverse aortic constriction in C57bl6 mice followed by debanding after 8 weeks. This model closely mimics aortic stenosis and subsequent aortic valve replacement. After debanding, mice were treated with either G-CSF or saline injection. Granulocyte colony-stimulating factor treatment significantly improved systolic (ejection fraction 70.48 ± 1.17 vs. 58.41 ± 1.56%, P < 0.001) and diastolic (E/E 26.0 ± 1.0 vs. 32.6 ± 0.8, P < 0.05) function. Furthermore, cardiac fibrosis was significantly reduced in G-CSF-treated mice (collagen-I area fraction 7.96 ± 0.47 vs. 11.64 ± 1.22%, P < 0.05; collagen-III area fraction 10.73 ± 0.99 vs. 18.46 ± 0.71%, P < 0.001). Direct effects of G-CSF on cardiac fibroblasts or a relevant transdifferentiation of mobilized bone marrow cells could be excluded. However, a considerable infiltration of neutrophils was observed in G-CSF-treated mice. This sterile inflammation was accompanied by a selective release of interleukin-1 β (IL-1β) in the absence of other proinflammatory cytokines. In vitro experiments confirmed an increased expression of IL-1β in neutrophils after G-CSF treatment. Interleukin-1β directly induced the expression of the gelatinases matrix metalloproteinase-2 (MMP-2) and MMP-9 in cardiac fibroblasts thereby providing the regression of cardiac fibrosis.nnnCONCLUSIONnGranulocyte colony-stimulating factor treatment improves the cardiac function and leads to the regression of myocardial fibrosis after pressure unloading. These findings reveal a previously unknown mechanism of fibrosis regression. Granulocyte colony-stimulating factor might be a potential pharmacological treatment approach for patients suffering from congestive heart failure after aortic valve replacement, although further basic research and clinical trials are required in order to prove beneficial effects of G-CSF in the human organism.

Feasibility of everolimus-eluting bioresorbable vascular scaffolds in patients with chronic total occlusion

OBJECTIVEnThis study evaluates the feasibility of percutaneous coronary intervention with bioresorbable vascular scaffolds (BVSs) in chronic total occlusion (CTO) lesions.nnnBACKGROUNDnEverolimus-eluting BVSs represent a new approach to treating coronary artery disease, but experience with CTO is limited.nnnMETHODSnPatients with a previously diagnosed CTO who had been treated with BVS were included. Patients with unsuccessful CTO procedures and patients treated with drug-eluting stents were excluded. Difficulty of the CTO procedure was assessed by the J-score.nnnRESULTSnA total of 23 patients were included. Mean age was 60.4 ± 9.0 years, 17.4% were female, 91.3% suffered from hypertension and 34.8% from diabetes. Mean J-score was 1.7 ± 1.0. Median procedure time was 70 min (54-85), mean contrast volume was 213.5 mL (±94.2) and median fluoroscopy time was 19.1 min (13.1-30.0). A total of 64 BVSs were implanted with a mean number of 2.8 ± 1.0 BVSs per patient, a mean total BVS length of 64.8 ± 24.2 mm per lesion, and a mean BVS diameter of 3.1 ± 0.2 mm. Neither a scaffold-related dissection nor any other intra-procedural complication occurred. During a follow-up of 108 (79.5-214.5) days one in-scaffold thrombosis was noted 4 days after the CTO procedure due to a lack of dual antiplatelet therapy. No further major adverse cardiac events occurred.nnnCONCLUSIONnThese results suggest that BVS implantation in CTO lesions can be performed with good procedural success and reasonable clinical short-term outcome in highly selected cases.

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.

Molecular basis of disturbed extracellular matrix homeostasis in stress cardiomyopathy

Sebastian Szardien , Helge Mollmann , Matthias Willmer , Christoph Liebetrau , Sandra Voss , Christian Troidl , Jedrzej Hoffmann , Johannes Rixe , Albrecht Elsasser , Christian W. Hamm , Holger M. Nef a,b,c,⁎ a Kerckhoff Heart Center, Department of Cardiology, D-61231 Bad Nauheim, Germany b Department of Experimental Cardiology, Franz-Groedel-Institute of the Kerckhoff Heart Center, D-61231 Bad Nauheim, Germany c University of Giessen, Medical Clinic I, Department of Cardiology, D-39392 Giessen, Germany d Department of Cardiology, Klinikum Oldenburg, D-26121 Oldenburg, Germany