Abstract Aims Cholesterol chrystals (CC) represent a feature of advanced plaque remodeling. Optical coherence tomography (OCT) allows for detailed morphological assessment of the culprit lesion, including the presence of CCs, in vivo. Since CCs have been identified as prognostically relevant plaque feature in coronary artery disease (CAD), the present analysis aims to further characterize their impact on adverse cardiovascular outcome in a large cohort of patients, presenting with acute coronary syndrome (ACS). Methods Within the translational OPTICO-ACS study program, 371 consecutive ACS-patients were included into the final analysis. OCT-characteristics, including the presence of CCs, were assessed by a standardized CoreLab analysis following universal consensus standards for OCT-derived plaque features. All patients were followed up for 12 months after the index event and major adverse cardiac events (MACE) consisting of death, myocardial infarction, target vessel revascularization plus re-hospitalization due to unstable or progressive angina pectoris were documented. Results 215 patients (58.1%) presented with cholesterol chrystals (CCs) at the culprit lesion. Plaque rupture (RFC-ACS) represented the primary ACS-causing pathophysiology (75.3%) in those patients. Further, the presence of CCs was associated with other high-risk features within the culprit lesion, i.e. the presence of thin cap fibroatheroma (77.7% vs. 63.2%; p<0.05), plaque calcification (80.5% vs. 67.1; p<0.01) and microchannels (80.1% vs. 70.1; p<0.05) as well as an increased area stenosis (0.77 vs. 0.73 mm2; p<0.01) and a greater maximum lipid arc (282.8 vs. 242.6°; p<0.01) as compared to culprit lesions free of CCs. Of note, there was a strong association among the occurrence of macrophages within the plaque and cholesterol crystals. Finally, and most importantly MACE during 12 months follow-up, consisting of cardiac death, myocardial infarction, target vessel revascularization and re-hospitalization due to progressive or unstable angina pectoris, occurred with nearly twice the frequency in CC-patients (20.3% vs. 10.6%; p<0.01) as compared to patients without CCs at the culprit site. Conclusion The present analysis introduces cholesterol chrystals as a novel prognostically relevant high-risk plaque feature allowing individual risk stratification for patients after ACS. Funding Acknowledgement Type of funding sources: None.
Abstract Background Prior data showed associations of circulating Proprotein Convertase Subtilisin / Kexin type 9 (PCSK9) and inflammatory/anti-fibrotic Cellular Communication Network factor 1 (CCN1) at index ST-segment elevation acute myocardial infarction (STEMI) with left ventricular ejection fraction at 6 and 12 months, respectively and for CCN1 also with infarct size. Purpose PCSK-9, CCN1 and reference biomarkers high-sensitivity Troponin T (hsTNT) and N-terminal pro-brain natriuretic peptide (NTproBNP) were measured in patients from the CLEVER-ACS trial (clinicaltrials.gov NCT01529554) at presentation with STEMI and correlated with clinically relevant cardiac magnetic resonance (CMR) parameters at 30 days. Methods Associations between baseline biomarkers (PCSK-9, CCN1, hsTNT, NTproBNP) and CMR parameters at 30 days were evaluated using Spearman correlation and linear regression analysis (dichotomised at their median). Receiver operating characteristic (ROC) and area under the curve (AUC) were determined for significant values based on correlation analysis; AUC > 0,7 considered relevant. CMR parameters comprised left ventricular structural and functional parameters including scar mass and microvascular obstruction. Results We identified 56 STEMI patients (mean age 61.7 ± 11.2 (SD) years) who completed 30 days follow-up with biomarker data. Among biomarkers, significant associations with CMR parameters were only found for hsTNT, and NTproBNP. The strongest associations were found for left ventricular ejection fraction (LVEF; hsTNT RSp =-0.66; NTproBNP RSp =-0.57), left ventricular scar (LVSCAR; hsTNT RSp =0.58; NTproBNP RSp =0.56) and scar mass (SM; hsTNT RSp =0.65; NTproBNP RSp =0.55). Conversely, left ventricular end-diastolic volume index (LVEDVI; hsTNT RSp =0.47; NTproBNP RSp =0.32), left ventricular end-systolic volume index (LVESVI; hsTNT RSp =0.51; NTproBNP RSp =0.39) and microvascular obstruction (MVO; hsTNT RSp =0.34; NTproBNP RSp =0.34) were significantly, albeit only modestly associated. ROC and AUC analysis yielded relevant associations of biomarkers with CMR parameters LVEF (hsTNT=0.79; NTproBNP=0.81), LVSCAR (hsTNT=0.84; NTproBNP=0.76) and scar mass (hsTNT=0.83; NTproBNP=0.78). Furthermore, relevant associations of biomarkers with CMR were found for LVEDVI (hsTNT=0.79; NTproBNP=0.72), LVESVI (hsTNT=0.84; NTproBNP=0.72) and MVO (hsTNT=0.72; NTproBNP=0.71). Conclusion Baseline levels of hsTNT and NT-proBNP are strong predictors for functional and dimensional CMR parameters of the left ventricle including clinically relevant imaging surrogates of myocardial injury shortly after STEMI.ROC LVEF
Abstract Background/Introduction Severe tricuspid regurgitation (TR) is associated with progressive right atrial (RA) and ventricular (RV) dilation, dysfunction and increased mortality. Risk factors impacting the long-term prognosis in patients with severe TR are largely undetermined. Purpose Herein, we aimed to identify risk factors associated with long-term mortality in patients with severe TR and implement a novel risk stratification strategy based on an individual five-year mortality prediction score. Methods From January 2013 to December 2017, 1238 patients with severe functional TR were enrolled in the TRuE-registry, of which 914 with a complete dataset were included in the present study. Echocardiographic quantification of RV-function and size included measurements of tricuspid annular plane systolic excursion (TAPSE), the end-diastolic basal (RVDbasal) and longitudinal diameters (RVDlong) and the RA-volume index (RAVI). The cohort was randomly divided into a development (n=610) and validation (n=304) sample. A risk stratification model was developed using a multivariable Cox regression. Results The variables statistically significant to predict five-year-mortality, included in the final model and used as score parameters were: age, COPD, dialysis, pulmonary artery systolic pressure, RAVI, TAPSE RVDbasal, RVDlong and systolic hepatic vein flow reversal (sHVFR). Progressive enlargement of RV and RA and concomitant sHVFR was associated with higher values of hazard ratios (HR, Figure A). Based on the HR values, a risk score with 3 categories was developed (Figure B): low (0–2), intermediate (3–5), high (6–16). Among the risk groups, Kaplan Meier estimates of all-cause mortality at 5 years were 18%, 52% and 84% respectively (p<0.001; https://thetruerisk.com). The score showed good discrimination, with a concordance index of 0.75. At internal validation, a good agreement between the derivation and validation datasets indicated a good calibration of the survival curves. Implementation of a long term risk score Conclusion The present study demonstrates the prognostic impact of comorbidities and right heart remodeling on long-term mortality in patients with severe TR. The presented risk score provides an easy and accurate estimation of long-term mortality and may thus help to guide therapeutic decision-making in this difficult group of patients.
Abstract Introduction Cardiogenic shock (CS) is the leading cause of death due to acute coronary syndromes (ACS) and mortality remained nearly unchanged over the past two decades. Immediate revascularization of the infarct-related artery is the treatment strategy of choice to reduce CS-related mortality, but early identification of patients at high risk of CS and death is challenging. The adrenomedullin (ADM) system modulates vascular tone and endothelial barrier function and monitoring its activity may enhance early risk assessment of ACS patients prone to experience CS and ultimately death. Methods In 4293 ACS patients, prospectively recruited at 4 Swiss university hospitals, the 3 major ADM system components were assessed in plasma at the time of acute presentation by blinded study personnel: ADM-glycine (its inactive substrate), peptidylglycine α-amidating monooxygenase (PAM; the ADM-amidating enzyme), and the biologically active ADM-amide (bio-ADM). Patients were monitored for in-hospital development of CS and followed at 30 days and 1 year with external event adjudication. The relationship of each ADM system component with features of CS pathophysiology (such as proxies for the decrease in cardiac contractile mass, increase in cardiac stress or systemic inflammation) was estimated by means of partial correlation coefficients. Multivariable-adjusted regression models were fit to assess their independent association with CS development and death. Results Baseline ADM-glycine, PAM and bio-ADM levels were tightly linked to features of CS (Fig. 1), with each ADM system component associating with in-hospital CS (odds ratio, 95% confidence interval [CI] per doubling in each, 2.04, 1.79-2.33, P<.001; 1.91, 1.63-2.23, P<.001; 1.72, 1.11-2.66, P=.016). The association of each marker with CS remained robust after adjusting for established risk factors for in-hospital development of CS, including all hemodynamic-, patient-, and procedure-related variables informing the ORBI risk score (1.65, 1.35-2.00, P<.001; 1.50, 1.26-1.77, P<.001; and 1.87, 1.13-3.11, P=.015). Notably, integration of ADM-glycine, PAM, and bio-ADM into the ORBI risk prediction model conferred increased discriminative performance for the prediction of in-hospital CS (AUC, 0.76 vs. 0.81, P<.001), ranking the ADM system second among all variables informing the score (Fig. 2). While both ADM-glycine and bio-ADM independently associated with mortality risk at 30-days (multivariable-adjusted hazard ratio per doubling, 95% CI, 1.93, 1.54-2.42, P<.001; and 1.81, 1.34-2.44, P<.001) and 1-year (1.41, 1.18-1.68, P<.001; and 1.52, 1.24-1.87, P<.001), PAM showed no association with these outcomes (P>.05). Conclusions Monitoring key regulators of the ADM system improves early risk assessment of ACS patients at high risk of CS, with admission ADM-glycine and bio-ADM representing independent risk factors for 30-day and 1-year mortality post-ACS.
Abstract Introduction Coronary microvascular dysfunction has been associated with adverse cardiovascular events following acute myocardial infarction. This study evaluates the role of the angiography-derived index of microcirculatory resistance (angio-IMR) in predicting myocardial damage in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). Material and Methods In this post hoc analysis of the Controlled Level Everolimus in Acute Coronary Syndromes (CLEVER-ACS) trial, the associations between post-PCI angio-IMR of infarct-related coronary arteries (IRAs) and infarct size, microvascular obstruction (MVO), and left ventricle ejection fraction (LVEF) at 30 days as assessed with cardiac magnetic resonance (CMR) imaging were investigated. High post-PCI angio-IMR value was defined as a value >40 U. In non-IRAs angio-IMR was measured before the IRA-PCI. Results A total of 52 IRAs and 94 non-IRAs of 52 patients were included in the analysis. Post-PCI Angio-IMR was 41.5 (IQR 28.5–55.7) U in IRAs and pre-PCI Angio-IMR was 43.7 (31.7–54.0) U in non-IRAs (p = 0.70). Patients with high post-PCI angio-IMR (52%) exhibited a larger myocardial infarct size (36.0 [23.0–52.5] g vs. 14.5 [6.50–26.5] g, p < 0.001) and a lower LVEF (46.5 [39.5–49.5] % vs. 55.0 [48.0–61.4] %, p = 0.002) at 30 days as compared to those with low post-PCI angio-IMR values. Post-PCI angio-IMR correlated with myocardial infarct size (r = 0.45, p = 0.001) and extent of MVO (r = 0.40, p = 0.004) at 30 days. Post-PCI angio-IMR predicted myocardial infarct size (AUC = 0.78 [0.65–0.92], p = 0.001) and extent of MVO (AUC = 0.74 [0.60–0.89], p = 0.009) at 30 days. Conclusion In patients with STEMI undergoing PCI, post-PCI angio-IMR was identified as independent predictor of myocardial infarct size and extent of MVO at 30 days. The assessment of post-PCI angio-IMR values may represent a novel tool for early risk stratification of patients with STEMI.Central illustration
Pathophysiology of coronary artery diseases 127duction (matching efficiency 95%, narterial group = 125, nvenous group = 250).In the arterial group, LAD was exclusively revascularized by using an arterial graft, in the venous group the LAD was revascularized by using a venous graft.The survival curves started to diverge in the complete cohort (Figure 1A) as well as in the propensity score-matched cohort (Figure 1B) five years after the surgery.Survival was significantly lower in patients with venous LAD revascularization (crude logRank p<0.001, propensity score-matched logRank p=0.043).There were no significant differences noted in perioperative myocardial infarction (p=0.839),rethoracotomy rate (p=0.887), and perioperative stroke (p=0.479).Discharge medication rate of low-dose aspirin was similar (p=0.552).Figure 1.A) Kaplan-Meier plot of the crude data B); Kaplan-Meier plot of the 1:2 propensity score matched cohort. Conclusion:The superiority of arterial grafting when revascularizing the LAD gets evident after five years of the CABG surgery and persists in the long-term follow-up.
