Abstract Background All patients with type A aortic dissections, regardless of age, are recommended urgent aortic surgery. However, studies exploring long term outcomes in survivors are sparse, and especially, the significance of age on long-term outcomes remain unclear. Purpose We described and compared incidences across age groups of post-discharge readmission, repeated aortic surgery, and death in patients who survived surgery and hospitalization for type A aortic dissection. Methods Using data from Danish nationwide registries, we identified patients hospitalized with Stanford type A aortic dissections from 2006–2018. Survivors of hospitalization and surgery on the ascending aorta and/or aortic arch comprised the study population (Figure 1). Using cumulative incidence plots taking death into account as a competing risk and Cox regression analysis, we described long-term outcomes (rehospitalizations, repeated aortic surgery, and death) and compared different age groups. The diagnosis of type A aortic dissection in the registries used, was validated from 191 clinical records to have a positive predictive value of 94.8%. Results Of 606 initial survivors of surgery and hospitalization with type A aortic dissection, 236 (38.9%) were <60 years old (group I), 194 (32.0%) were 60–69 years old (group II), and 176 (29.1%) were >69 years old (group III). Figure 2 shows cumulative incidences of outcomes according to age. During the first year, 62.5% were re-hospitalized (median number of days hospitalized was 2 days (IQR 1–8 days) and 1.4% underwent repeated aortic surgery with no significant differences across age groups (P=0.68 and P=0.39, respectively). Further, 5.9% died (group I: 3.0%, group II: 8.3%, group III: 7.4%, P=0.04). After 10 years of follow up, 8.0% had undergone repeated aortic surgery (group I: 11.5%, group II: 8.5%, group III: 1.6%, P=0.04) and 10.2% (group I), 17.0% (group II), and 22.2% (group III) had died (P=0.01). In adjusted analyses, no age differences were found in one-year outcomes, while age >69 years (group III) compared with age <60 years (group I) was associated with a lower rate of repeated aortic surgery (hazard ratio 0.17, 95% confidence interval 0.04–0.78) and a higher rate of all-cause mortality (hazard ratio 2.44, 95% confidence interval 1.37–4.34) in the 10-years analysis. Conclusion Among survivors of type A aortic dissections, rehospitalizations the first year after discharge were common among all age groups, but survival was high. Repeated aortic surgery was rare, and significantly more common among younger than older patients. Evaluations of quality of life in survivors of type A aortic dissections are needed. Funding Acknowledgement Type of funding sources: None.

Abstract Background The Heart Failure Collaboratory (HFC) has developed a medical therapy score which integrates types and doses of guideline-directed pharmacotherapies in patients with systolic heart failure, providing a measure of treatment quality. In clinical trials, this score may help determine the additive effect of new treatments. In the Danish Study to Assess the Efficacy of Implantable Cardioverter Defibrillators (ICDs) in Patients with Non-ischaemic Systolic Heart Failure on Mortality (DANISH) trial, ICD implantation did not provide an overall survival benefit in patients with non-ischaemic systolic heart failure. Purpose Adding four years of additional follow-up to the DANISH trial, we examined the effect of ICD implantation according to baseline modified HFC (mHFC) medical therapy score. Methods In the DANISH trial, 1,116 patients with non-ischaemic systolic heart failure were randomised to receive an ICD (N = 556) or usual clinical care (N = 560, control group). The primary outcome was death from any cause. In the mHFC score, patients were assigned a score for each drug class of the original cornerstones of systolic heart failure treatment (renin-angiotensin-system inhibitor, beta-blocker, and mineralocorticoid receptor antagonist). The maximum score was 100%, corresponding to optimal medical therapy with all three types of medication (=>50% of target dose). Results The median mHFC score at baseline was 67% (25th-75th percentile, 67%-100%; range, 17%-100%). During a median follow-up of 9.5 years, the ICD group did not have significantly lower all-cause mortality compared with the control group (hazard ratio [HR] 0.89 [95% CI, 0.74-1.08]). The results were independent of the mHFC score at baseline (mHFC score = < median: HR 0.91 [95% CI, 0.70-1.19]; mHFC score > median: HR 0.87 [95% CI, 0.66-1.14]; P for interaction, 0.94). Similarly, ICD implantation did not reduce the rate of cardiovascular death overall (HR 0.87 [95% CI, 0.70-1.09]), and this association was not modified by the mHFC score (mHFC score = < median: HR 0.90 [95% CI, 0.65-1.24]; mHFC score > median: HR 0.84 [95% CI, 0.61-1.15]; P for interaction, 0.89). The ICD group had a significantly lower rate of sudden cardiovascular death in the overall population (HR, 0.60 [95% CI, 0.40-0.92]), and this association was not modified by the mHFC score (mHFC score = < median: HR 0.72 [95% CI, 0.40-1.29]; mHFC score > median: HR 0.53 [95% CI, 0.28-0.99]; P for interaction, 0.59). See Figure for results. Conclusions In this extended follow-up study of the DANISH trial, ICD implantation did not provide an overall survival benefit in patients with non-ischaemic systolic heart failure regardless of baseline medical heart failure therapy, assessed by the mHFC score.Modified HFC score in the DANISH trial

Abstract Background The optimal management of patients with non-ST elevation acute coronary syndromes (NSTEACS) remains a challenge. The merits of both computed tomography angiography (CTA) as a rule-out test for significant coronary artery disease and early invasive coronary angiography (ICA) are debated. Furthermore, there are limited data in older NSTEACS patients, who likely have more coronary artery calcification and are at higher risk of ACS-related complications. Methods This is a post hoc analysis of patients ≥75 years included in the Very Early Versus Standard Care Invasive Examination and Treatment of Patients with Non-ST-Segment Elevation Acute Coronary Syndrome Trial (VERDICT). The diagnostic accuracy of CTA was investigated in patients without previous coronary artery bypass grafting, renal dysfunction, or atrial fibrillation; the presence of a coronary artery stenosis ≥50% determined by ICA was used as reference. Patients were randomised to very early ICA within 12 hours of diagnosis or standard care (ICA within 48–72 hours of diagnosis) and followed for up to five years. The primary endpoint was the composite of all-cause mortality, nonfatal recurrent MI, hospital admission for refractory myocardial ischaemia or hospital admission for heart failure. Results From November 2010 to June 2016, 2147 patients were included in the VERDICT trial. Of these, 452 (21%) patients were ≥75 years of age. Most older patients had a GRACE score >140 (n=388, 88.8%). At the time of admission, older patients had lower levels of haemoglobin, estimated glomerular filtration rate, and left ventricular ejection fraction, and more often displayed elevated troponins and electrocardiogram changes indicating new ischaemia, than those <75 years. Of patients ≥75 years of age, 161 (35.6%) underwent CTA before ICA. Older patients had significantly higher calcium scores than younger patients (1187±1445 vs. 499±858 Agatston units, p<0.001). 19% of CTAs excluded significant coronary artery disease. The negative predictive value of the CTAs was 94 (95% CI 79–99)% and the sensitivity was 98 (95% CI 94–100)%, figure 1. The primary endpoint was observed more frequently in patients ≥75 years as compared to younger patients (n=222, 49% vs. n=390, 23%, p<0.001), even after adjustment for allocated treatment (adjusted HR 2.65, 95% CI 2.25–3.13, p<0.001). Among older patients randomised to very early ICA, there were no differences in the cumulated number of primary endpoints compared to older patients randomised to standard ICA (log-rank p=0.36), figure 2. Conclusion Among patients ≥75 years old with NSTEACS, CTA showed a high diagnostic accuracy. A very early ICA within 12 hours of diagnosis did not improve long-term composite outcome in these older patients with NSTEACS. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Rigshospitalets Research Foundation

Abstract Background In patients with ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI), reperfusion injury accounts for a significant part of the final infarct size, which is directly related to patient prognosis. In animal studies brief periods of ischemia in non-infarct related coronary arteries protects the myocardium via remote ischemic perconditioning. Fractional flow reserve (FFR) measures functional significant coronary stenosis which may offer remote ischemic perconditioning of the myocardium. It has not previously been investigated if FFR-significant stenosis in non-culprit myocardium offers cardioprotection following STEMI. Purpose To investigate cardioprotective effect of FFR-significant multivessel disease (MVD) on final infarct size and myocardial salvage in a large contemporary cohort of patients with ST-segment elevation myocardial infarction (STEMI). Methods and results We included 509 patients with STEMI from the DANAMI-3 trial, divided into three groups: 388 (76%) patients had single vessel disease (SVD), 34 (7%) had non-FFR-significant MVD and 192 (17%) had FFR-significant MVD. CMR was performed at baseline and three months after primary PCI. There was no difference in final infarct size; mean infarct size (% left ventricular mass) SVD 9±3%; non-FFR-significant MVD 9±3%; and FFR-significant MVD 9±3%, p=0.95, or in myocardial salvage index (MSI) between groups, calculated as (area-at-risk – infarct size)/area-at-risk; mean index (%) SVD 67±23%; non-FFR-significant MVD 68±19%; and FFR-significant MVD 67±21%, p=0,99. In multivariable regression analyses FFR-significant MVD was not associated med larger MSI (p=0.84) or lower infarct size (p=0.60). Figure 1. A. Late gadolinium (LGE) cardiac magnetic resonance (CMR) image of a mid-ventricular short-axis slice. Hyperintense signals (arrow) shows contrast enhancement in the anterior-septal segments, indicating myocardial infarction (MI). B. Same patient. T2-weighted image of the same mid-ventricular short-axis slice. Hyperintense signals (arrows) shows edema in the anterior-septal segments. Conclusions FFR-significant functional MVD of non-culprit myocardium does not offer cardioprotection in patients following STEMI.

Background: C-terminal provasopressin (copeptin) is a marker of hyperosmolar- ity and endogenous stress and has demonstrated promising prognostic potential in heart failure (HF) and after acute myocardial infarction. Levels of copeptin are known to peak few hours after chest pain onset and then decline. Yet admission levels of copeptin have not been investigated in a large cohort of patients with ST-segment elevation myocardial infarction (STEMI). Purpose: The aim of this study was to examine the associations of admission copeptin with long- and short-term all-cause mortality, and hospital admission for HF in STEMI patients. Methods: This substudy was conducted as part of The Danish Study of Optimal Acute Treatment of Patients with STEMI (DANAMI-3). Blood samples for analyses of copeptin were obtained immediately upon arrival in the catheterization labora-tory before primary percutaneous coronary intervention was performed. Admis- sion levels of copeptin were divided into quartiles and the Kaplan Meier survival curves were compared across quartiles by the log-rank test. We assessed all the outcome events using Cox proportional hazard models adjusted for age, gender, time since onset of symptoms, heart rate, estimated glomerular filtration rate, an- giographic thrombolysis in myocardial infarction flow, diabetes, hypertension and history of; myocardial infarction, congestive HF, stroke and smoking. Results: Intotal1119patientswereincluded.Themedianagewas62years(25th to 75th percentiles; 53–70) and 76% were men. Blood samples were obtained with a median interval of 2.8 hours (25th to 75th percentiles; 2.1–4.4) after onset of symptoms. Levels of copeptin were significantly higher in the group of patients presenting within 0 to 3 hours after onset of symptoms (median 99.4 pmol/L, 25th to 75th percentiles; 32.0–208.1) compared with patients presenting in the interval of 3 to 6 hours (median 55.2 pmol/L, 25th to 75th percentiles; 16.3–159.1) and with patients presenting after 6 hours (median 25.2 pmol/L, 25th to 75th percentiles; 10.3–72.0; p < 0.0001). During a median follow-up of 1078 days (25th to 75th percentiles; 884–1272) 79 (7.1%) died, 22 (2.0%) died within 30 days and 38 (3.4%) were admitted for HF. The number of deaths increased with higher copeptin quartile; 13 (4.7%) in 1st quartile, 14 (5.0%) in 2nd quartile, 22 (7.9%) in 3rd quartile and 30 (10.7%) in 4th quartile (Figure). A doubling of copeptin was, in adjusted models, associated with an increased risk of long-term mortality (hazard ratio 1.15, 95% confidence interval [CI] 1.01–1.31) and mortality within 30 days (hazard ratio 1.68, 95% CI 1.23–2.28), whereas copeptin was not significantly associated with increased risk of hospital admission for HF (hazard ratio 1.10, 95% CI 0.92–1.32). with STEMI, admission copeptin was associated with increased short and long-term mortality. CNP is involved in the regulation of vascular tone, remodeling and regeneration. Purpose: We assessed the functional significance of endothelium-derived CNP in the regulation of blood pressure in vivo. Methods: We generated and analyzed vascular endothelial cell-specific CNP knockout (CNP ecKO) and vascular smooth muscle cell-specific CNP receptor, guanylyl cyclase-B (GC-B), knockout (GC-B smcKO) mice. Results: Both CNP ecKO and GC-B smcKO mice showed neither the skeletal abnormality nor the early mortality observed in systemic CNP or GC-B knockout mice. Significantly elevated blood pressures and an enhanced acute hyperten-sive response to nitric oxide synthetase inhibition were observed in CNP ecKO mice. Acetylcholine (ACh)-induced, endothelium-dependent vasorelaxation was in rings of mesenteric artery isolated from CNP ecKO mice. Further- more, when we pretreated mesenteric arteries with L-NAME and the cyclooxygenase (COX) inhibitor indomethacin, the impairment of ACh- induced vasorelaxation was enhanced in CNP ecKO arteries, suggesting that the of endothelium-dependent in CNP ecKO mice NO- and prostaglandin-independent pathways, possibly an endothelium-derived hyperpolarization factor (EDHF) system. found that endothelin-1 gene in vascular endothelial mice, showed blood in littermates. CNP-induced acute was nearly completely abolished in mesen- teric arteries from GC-B smcKO mice. Consistent with this finding, GC-B smcKO mice exhibited marked attenuation in acute hypotensive effects induced by intra- venous administration of CNP. Conclusions: These results indicate that endothelium-derived CNP maintains Background: MicroRNAs (miRNAs) are small noncoding RNAs that block trans- lation or induce degradation of mRNA and thereby control patterns of gene expression. Although several miRNAs have been shown to control important pro- cesses that contribute to the pathophysiological consequences of atrial fibrillation, the optimal delivery method of miRNAs is not clinically well estabilished. Exosome work as a cargo which contains and delivers bioactive molecults critical to intracellular signaling. Objective: This study evaluated whether the modified exosome by loading spe- cific miRNAs could control AF in pacing induced tachycardia model. Methods: Exosome was isolated from peripheral blood of paroxysmal supraven- tricular tachcyardia patients (Exo-control) by ultracentrifugation. Peripheral blood-derivedexosomewasexaminedbyelectronmicroscopy,andtheexpressionofex-osomemarkerCD63wasanalyzedbyWesternblotandflowcytometry.miRNA1and133awereloadedtoExo-controlbyelectrophoresisandtransfectionmethod(Exo-miRNA).PKH26-labeledexosomesweredeliveredtoHL-1atrialcardiomy-ocytesat24hoursbeforetheinitiationoftachypacing(5Hz).TheeffectsofExo-controlandExo-miRNAontachypacingmodelofHL-1atrialcardiomyocyteswereexaminedusingapatchclamp,aconfocalCa2+imaging,immunoblottingandim-munofluorescencestaining. Results: In tachypacing model of HL-1 atrial cardiomyocytes, Exo-miRNA 1 and 133a prevented tachypacing induced shortening of action potential duration, loss of Ca2+transient amplitude, and loss of L-type Ca2+ current. However, Exo- control had no effect. Tachypacing induced contractile dysfunction was prevented by Exo-miRNA 1 and 133a, but not by Exo-control. Autophagy marker (eg. LC3) and depolymerization of microtubules through Histone Deacetylase-6 (HDAC-6) were increased by the duration of tachypacing. The increase of autophagy and depolymerization of microtubules were prevented by Exo-miRNA 1 and 133a, but not by Exo-control. Conclusions: Exosome loaded with miRNA 1 and 133a protects against AF- related atrial remodeling. This result suggesting the novel role of exosome as a therapeutic miRNA delivery system for the treatment of arrhythmia. Recent electrophysiological findings have demonstrated that LBBB is a heterogeneous electrical disease. Therefore, its effect on mechanical contraction may be diverse. Purpose: The aim of this study was to characterize electrical and mechanical dyssynchrony and to analyze their relationships in LBBB patients. Methods: We retrospectively analyzed data of 994 patients who underwent my- ocardial perfusion imaging (MPI) SPECT/CT between April 2009 and May 2011. Forty-three patients fulfilled Strauss criteria for LBBB. Twenty-four healthy con- trols formed a reference group. The 12-lead-ECG recorded along with MPI pro-tocol was reanalyzed using vectorcardiography (VCG) to characterize features of electrical dyssynchrony. Left ventricular (LV) mechanical dyssynchrony was described with MPI phase histogram bandwidth (PHBW) or standard deviation values above limit of the highest normal. Univariate and multivariate regression analyses were performed to find out associations between features representing electrical alterations and synchronism of mechanical contraction. We determined receiver operating curves to evaluate diagnostic performance for potential predic- tors of mechanical dyssynchrony and to define optimal cut-off values. Results: In addition to QRS prolongation, the main VCG features of LBBB were elongated, narrowed, downward and posteriorly pointing QRS-loop and signs of LV-hypertrophy. Sixty percent of LBBB patients had mechanical dyssynchrony. QRSd (QRSd; r=0.70, p < 0.001), magnitude of QRS-vector (r=0.41, p < 0.001), QRS-angle in horizontal plane (r=0.54, p < 0.001), QRST-angle (r=0.46, p < 0.001) and Cornell voltage (CorV; r=0.56, p < 0.001)) correlated significantly with PHBW. QRSd ( β =0.91, p < 0.001), QRST-angle ( β =-0.52, p=0.002) and CorV ( β =0.31, Background: Coronary microvascular dysfunction (CMD) is derived from dif- ferent mechanisms: endothelial-dependent CMD (microvascular spasm), and endothelial-independent CMD (syndrome X). While medical treatment is differ- ent, whether they coexist in patients with CMD is unknown. Purpose: The purpose of to examine whether endothelial- dependent and -independent CMD coexist in patients with CMD. Methods: In 46 female patients with chest pain and unobstructed coronary arter- ies, a Doppler guide-wire was inserted into the left anterior descending coronary artery. After administration of acetylcholine (ACH) into the left coronary coronary blood flow (CBF) obtained. Coronary flow reserve (CFR) mea-sured after

AIMSThe aim of this study was to evaluate whether a staged in-hospital complete revascularisation strategy increases the risk of serious bleeding events in patients with ST-segment elevation myocardial infarction (STEMI) and multivessel disease.METHODS AND RESULTSThe DANAMI-3-PRIMULTI trial investigated whether a staged in-hospital complete revascularisation strategy improved outcome in patients with STEMI and multivessel disease. In this substudy, we investigated potential bleeding complications related to a second in-hospital procedure. Bleedings were assessed using BARC and TIMI criteria. Six hundred and twenty-seven (627) patients were randomised 1:1 to either PCI of the infarct-related artery (IRA) only (n=313) or complete revascularisation during a staged procedure before discharge (n=314). We found no significant difference in TIMI major+minor bleedings related to the primary PCI. There were neither major nor minor bleedings in relation to the second procedure in the complete revascularisation arm. There were significantly more in-hospital minimal+medical attention bleedings in the group randomised to complete revascularisation (61.5% vs. 49.5% in the IRA-PCI only group, p=0.003), but no difference in admission time or one-year mortality (2.2% complete revascularisation-group vs. 2.6% IRA-PCI only group, p=0.8).CONCLUSIONSIn multivessel diseased STEMI patients, a staged complete in-hospital revascularisation strategy or any second in-hospital procedure did not result in an increase in serious bleeding events.

OBJECTIVES This study sought to assess the association between abnormal glucose metabolism and abnormal coronary flow reserve (CFR) in patients with a recent acute myocardial infarction (AMI).BACKGROUND Mortality and morbidity after AMI is high among patients with abnormal glucose metabolism, which may be related to abnormal microcirculation.METHODS We studied 183 patients with a first AMI. In 161 patients with no history of diabetes mellitus (DM), an oral glucose tolerance test was performed, and patients were categorized according to World Health Organization criteria for whole blood glucose into 3 groups. After coronary angiography and revascularization, a comprehensive transthoracic echocardiogram and noninvasive assessment of CFR was performed in the distal part of left descending artery, as an indicator of microvascular function. Adenosine was administered by intravenous infusion (140 mu g/kg/min) to obtain the hyperemic flow profiles. The CFR was defined as the ratio of hyperemic to baseline peak diastolic coronary flow velocities.RESULTS Median CFR was 1.9 (interquartile range [IQR] 1.4 to 2.4], and 109 (60%) patients had a CFR <= 2. The lowest CFR was seen in patients with a history of DM (1.4 [IQR 1.4 to 1.7], n = 22) and in patients with newly diagnosed DM (1.6 [IQR 1.3 to 2], n = 39), whereas CFR did not differ in patients with abnormal glucose tolerance (2.1 [IQR 1.4 to 2.6], n = 58) and in patients with normal glucose tolerance (2.2 [IQR 1.7 to 2.6], n = 62). In a stepwise logistic regression model adjusting for age, sex, site and size of AMI, heart rate, risk factors of the metabolic syndrome, degree of angiographic evidence of coronary artery disease, and medical therapy, newly diagnosed DM (odds ratio: 3.0) and a history of DM (odds ratio: 9.9) remained significant predictors of CFR <2, whereas impaired glucose tolerance was not.CONCLUSIONS CFR is decreased in patients with known or newly diagnosed DM even after adjustment of possible confounders, whereas CFR in patients with impaired glucose tolerance seems less affected. (Coronary Flow Reserve and Glucometabolic State [CFRGS]; NCT00845468) (J Am Coll Cardiol Img 2009; 2: 1159-66) (C) 2009 by the American College of Cardiology Foundation

A.C. Falkentoft1, R. Roerth1, K. Iversen2, D.E. Hoefsten1, H. Kelbaek1, L. Holmvang1, M. Frydland1, C. Torp-Pedersen3, K. Kofoed1, J.P. Goetze4, T. Engstroem1, L. Koeber1. 1Rigshospitalet Copenhagen University Hospital, Department of Cardiology, Copenhagen, Denmark; 2Herlev Hospital, Department of Cardiology, Herlev, Denmark; 3Aalborg University, Department of Health, Science and Technology, Aalborg, Denmark; 4Rigshospitalet Copenhagen University Hospital, Department of Clinical Biochemistry, Copenhagen, Denmark