Acoustic-based rule out of stable coronary artery disease: the FILTER-SCAD trial.

BACKGROUND AND AIMS: Overtesting of low-risk patients with suspect chronic coronary syndrome (CCS) is widespread. The acoustic-based coronary artery disease (CAD) score has superior rule-out capabilities when added to pre-test probability (PTP). FILTER-SCAD tested whether providing a CAD score and PTP to cardiologists was superior to PTP alone in limiting testing. METHODS: At six Danish and Swedish outpatient clinics, patients with suspected new-onset CCS were randomised to either standard diagnostic examination (SDE) with PTP, or SDE plus CAD score, and cardiologists provided with corresponding recommended diagnostic flowcharts. The primary endpoint was cumulative number of diagnostic tests at one year and key safety endpoint major adverse cardiac events (MACE). RESULTS: In total 2008 patients (46% male, median age 63 years) were randomised from October 2019 to September 2022. When randomised to CAD score (n=1002), it was successfully measured in 94.5%. Overall, 13.5% had PTP ≤5%, and 39.5% had CAD score ≤20. Testing was deferred in 22% with no differences in diagnostic tests between groups (p for superiority =0.56). In the PTP ≤5% subgroup, the proportion with deferred testing increased from 28% to 52% (p<0.001). Overall MACE was 2.4 per 100 person-years. Non-inferiority regarding safety was established, absolute risk difference 0.4% (95% CI -1.85 to 1.06) (p for non-inferiority = 0.005). No differences were seen in angina-related health status or quality of life. CONCLUSIONS: The implementation strategy of providing cardiologists with a CAD score alongside SDE did not reduce testing overall but indicated a possible role in patients with low CCS likelihood. Further strategies are warranted to address resistance to modifying diagnostic pathways in this patient population.

Left atrial functional measurements' utility in predicting long-term risk of atrial fibrillation after isolated CABG.

BACKGROUND: Atrial fibrillation (AF) is the most common cardiac arrhythmia following coronary artery bypass grafting (CABG). We hypothesized that measures of left atrial (LA) function would be useful in predicting AF in patients undergoing CABG. METHODS AND RESULTS: In the study, 611 patients were included after CABG. All patients had echocardiograms performed preoperatively and LA functional measurements were assessed. These measurements were LA maximum volume index (LAVmax), LA minimum volume index (LAVmin) and LA emptying fraction (LAEF). The endpoint was AF occurring >14 days after surgery. During the follow-up period of a median of 3.7 years, 52 (9%) developed AF. The mean age was 67 years, 84% were male and the average left ventricle ejection fraction was 50%. Patients who developed AF had a lower CCS class and lower LAEF (40 vs. 45%), otherwise no clinical differences were observed between outcome groups. No functional LA measurements were significant predictors of AF in the whole CABG population. However, in patients with normal-sized LA (n = 532, events: 49), both LAEF and LAVmin were univariable predictors of AF. When the functional measurements were adjusted for the CHADS2 score, both LAVmin (HR = 1.07 [1.01-1.13], p = .014) and LAEF (HR: 1.02 [1.00-1.03], p = .023), remained significant predictors. CONCLUSION: No echocardiographic measurements were significant predictors of AF after CABG. In patients with a normal LA size, LAVmin as well as LAEF were significant predictors of AF.

Temporal Release of High-Sensitivity Cardiac Troponin T and I and Copeptin After Brief Induced Coronary Artery Balloon Occlusion in Humans.

BACKGROUND: Cardiac troponins (cTns) are the cornerstone of diagnosing acute myocardial infarction. There is limited knowledge on the duration of ischemia necessary to induce a measurable release of cTns or the very-early-release kinetics of cTns after an ischemic event. Copeptin may have a supplementary role in ruling out myocardial infarction early. We investigated the release of cTns and copeptin in the first hours after experimental balloon-induced ischemia in humans. METHODS: Thirty-four patients (median age, 60 years [interquartile range, 51-64]; 15 men, 43%) with angiographically normal coronary arteries were randomly assigned into 4 groups with different durations of induced myocardial ischemia (0, 30, 60, 90 s). Ischemia was induced by inflating a balloon in the left anterior descending artery between the first and second diagonal branch. Blood was collected before balloon inflation (baseline) every 15 minutes for the first 3 hours, and every 30 minutes for the next 3 hours. The cTns were analyzed by 3 high-sensitivity (hs) cTn assays: hs-cTnT (Roche), hs-cTnI (Siemens), and hs-cTnI (Abbott). Copeptin was analyzed by a sandwich immunoluminometric assay. RESULTS: None of the patients had any complications. Increased cTn concentrations were detected by all 3 assays, and the magnitude of the increase was associated with the duration of ischemia. Increased hs-cTnI (Siemens) concentrations were first detectable 15 minutes after 90-s ischemia (median 43.7% increase) and increased more steeply and had a higher peak than the other assays. Copeptin levels did not significantly change. Using the cTnT, hs-cTnI (Siemens), and hs-cTnI (Abbott) concentrations at 0 and 180 minutes, 1 (11%), 0, and 0 patients from the 60-s ischemia group and 5 (63%), 2 (25%), and 1 (11%) from the 90-s ischemia group, respectively, fulfilled criteria for a biochemical myocardial infarction. CONCLUSIONS: This study is the first to report the early-release kinetics of cTn concentrations after different durations of experimental coronary balloon occlusion in humans. All assays detected a cTn increase after only 30 s of ischemia. hs-cTnI (Siemens) rose faster and reached a higher peak. Copeptin levels did not change significantly. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03203057.

MR-proANP measured at admission is associated with incident atrial fibrillation in STEMI patients.

Atrial fibrillation (AF) is common following ST-segment elevation myocardial infarction (STEMI). Increased blood levels of mid regional pro atrial natriuretic peptide (MR-proANP) have been associated with a greater risk of incident AF. However, knowledge of the value of MR-proANP in predicting incident AF after STEMI is sparse. To assess whether MR-proANP measured at admission is associated with development of incident AF in patients with STEMI. 673 STEMI patients with no history of AF treated with primary percutaneous coronary intervention (pPCI) were prospectively enrolled from September 2006 to December 2008. Blood samples were drawn before the procedure. MR-proANP was measured by an automated processing assay. End point was incident AF. Median follow-up time was 5.5 years (interquartile-range 4.7-6.0), during which 63 patients developed AF. In a multivariable Cox regression model adjusted for relevant clinical and biochemical variables, MR-proANP was significantly associated with the development of AF (HR 1.18 per 100 pmol, 95% CI 1.11-1.28, p < 0.001). In a subgroup of patients who underwent echocardiography (N = 360), MR-proANP remained significantly associated with the development of AF (HR 1.39 per 100 pmol, 95% CI 1.13-1.71, p = 0.002) after adjusting for clinical and biochemical variables and left ventricular ejection fraction. When stratifying patients according to tertiles of MR-proANP, patients in the upper tertile displayed an 11 times greater risk of developing AF during follow-up as compared to patients in the lower tertile (HR 11.1, 95% CI 4.4-28.2, p < 0.001). Plasma MR-proANP measured at admission is an independent predictor of incident AF after STEMI.

Prognostic value of right ventricular echocardiographic measures in patients with heart failure with reduced ejection fraction.

PURPOSE: Right ventricular (RV) dysfunction is associated with poor outcome in patients with heart failure. In order to better predict mortality in this patient group we wanted to compare the prognostic value of conventional and advanced RV echocardiographic measures. METHODS: Echocardiographic examinations were retrieved from 701 patients. End point was all-cause mortality and follow-up 100%. RV parameters were measured offline in accordance with current guidelines. Speckle tracking was derived using the algorithm originally designed for the left ventricle. RESULTS: During follow-up (median: 39 months) 118 patients (16.8%) died. RV global longitudinal strain (GLS) and RV free wall strain (FWS) remained associated with mortality after multivariable adjustment independent of Tricuspid annular plane systolic excursion (TAPSE) (RV GLS: HR 1.07, 95%CI 1.02-1.13, p = 0.010, per 1% decrease) (RV FWS: HR 1.05, 95%CI 1.01-1.09, p = 0.010, per 1% decrease). This seemed to be caused by significant associations in men. All RV estimates provided prognostic information incremental to established risk factors and significantly increased C-statistics. CONCLUSIONS: RV GLS and FWS were associated with mortality in HFrEF patients after multivariable adjustment independent of TAPSE. TAPSE, however, remained as the strongest prognosticator in women. More research is needed to identify whether speckle tracking could be superior to conventional RV measures in identifying HFrEF patients with poor outcome.

Left Atrial Function Determined by Echocardiography Predicts Incident Heart Failure in Patients With STEMI treated by Primary Percutaneous Coronary Intervention.

OBJECTIVES: To assess the comparative effectiveness of left atrial (LA) functional parameters (left atrial emptying fraction (LAEF), left atrial expansion index (LAi) and minimal left atrial volume index (MinLAVI)) with that of LA volume index (LAVI) in predicting heart failure (HF) and death following ST-elevated myocardial infarction (STEMI). BACKGROUND: HF is common following STEMI. Enlarged LA volume as determined by echocardiography predicts adverse outcome following STEMI. However, whether echocardiographic parameters of LA function, such as LAEF, LAi and MinLAVI, are superior to LAVI for predicting prognosis following STEMI is unknown. METHODS AND RESULTS: A total of 369 patients with STEMI but without atrial fibrillation or HF who were treated with primary percutaneous coronary intervention were prospectively enrolled in the period between September 2006 and December 2008. Patients underwent echocardiography shortly after STEMI. The maximal and minimal LA volumes were measured using the biplane area-length method. LAVI, MinLAVI (minimal LA volume indexed to body surface area), LAEF ((maximal LA volume-minimal LA volume)/maximal LA volume), and LAi ((maximal LA volume-minimal LA volume)/minimal LA volume) were calculated. The endpoint was a composite consisting of HF or death from any cause. During a median follow-up of 66 months (interquartile range: 50-73 months), 112 patients reached the endpoint (68 HFs, 44 deaths). Following adjustment for clinical, biochemical and echocardiographic variables, only LAEF remained an independent predictor of the composite outcome, whereas LAVI did not (LAEF: HR 1.25, P = 0.043, per 1 SD decrease) (LAVI: HR 1.01, P = 0.91, per 1 SD increase). CONCLUSION: In patients with STEMI who were treated with primary percutaneous coronary intervention, LAEF, as measured by echocardiography shortly after infarction, was superior to LAVI in predicting incident HF and death.

Myocardial performance index is associated with cardiac computed tomography findings in patients with suspected coronary artery disease.

BACKGROUND: Studies suggest cardiac time intervals to be associated with cardiac ischemia. A novel method to assess cardiac time intervals by tissue Doppler echocardiography has been proposed. Cardiac time intervals can assess the myocardial performance index (MPI), which quantifies the proportion of time spent contributing effective myocardial work. We hypothesized that MPI associates with coronary artery lesions detected by cardiac computed tomography (CT) in patients suspected of coronary artery disease (CAD). METHODS: We investigated patients referred for cardiac CT under suspicion of CAD who had an echocardiogram performed. Curved m-mode tissue Doppler imaging was used to measure cardiac time intervals and MPI. The outcome was coronary artery lesions, defined as a calcium score > 400 and/or coronary artery stenosis (>70% luminal narrowing). Logistic regression was applied with multivariable models including: (a) SCORE chart risk factors and (b) SCORE chart risk factors, body mass index, dyslipidemia, familial history of CAD, diabetes mellitus, LVEF, and left ventricular mass index. RESULTS: Of 404 patients, 41 (10%) had a coronary artery lesion. Overall, 42% were male, mean age was 58 years, and LVEF was 58%. Patients with coronary artery lesions exhibited higher MPI than those without (0.52 vs. 0.44, P < .001). MPI associated with coronary artery lesions in unadjusted analyses (OR = 1.69 [1.30-2.19], per 0.1 increase), and this association persisted when adjusted for SCORE chart risk factors (OR = 1.55 [1.16-2.07], P = .003, per 0.1 increase), and additional risk factors (OR = 1.64 [1.11-2.41], P = .013, per 0.1 increase). CONCLUSION: Curved m-mode-derived MPI is associated with coronary artery lesions detected by cardiac CT in suspected CAD patients.

64Cu-DOTATATE PET/MRI for Detection of Activated Macrophages in Carotid Atherosclerotic Plaques: Studies in Patients Undergoing Endarterectomy.

OBJECTIVE: A feature of vulnerable atherosclerotic plaques of the carotid artery is high activity and abundance of lesion macrophages. There is consensus that this is of importance for plaque vulnerability, which may lead to clinical events, such as stroke and transient ischemic attack. We used positron emission tomography (PET) and the novel PET ligand [(64)Cu] [1,4,7,10-tetraazacyclododecane-N,N',N″,N‴-tetraacetic acid]-d-Phe1,Tyr3-octreotate ((64)Cu-DOTATATE) to specifically target macrophages via the somatostatin receptor subtype-2 in vivo. APPROACH AND RESULTS: Ten patients underwent simultaneous PET/MRI to measure (64)Cu-DOTATATE uptake in carotid artery plaques before carotid endarterectomy. (64)Cu-DOTATATE uptake was significantly higher in symptomatic plaque versus the contralateral carotid artery (P<0.001). Subsequently, a total of 62 plaque segments were assessed for gene expression of selected markers of plaque vulnerability using real-time quantitative polymerase chain reaction. These results were compared with in vivo (64)Cu-DOTATATE uptake calculated as the mean standardized uptake value. Univariate analysis of real-time quantitative polymerase chain reaction and PET showed that cluster of differentiation 163 (CD163) and CD68 gene expression correlated significantly but weakly with mean standardized uptake value in scans performed 85 minutes post injection (P<0.001 and P=0.015, respectively). Subsequent multivariate analysis showed that CD163 correlated independently with (64)Cu-DOTATATE uptake (P=0.031) whereas CD68 did not contribute significantly to the final model. CONCLUSIONS: The novel PET tracer (64)Cu-DOTATATE accumulates in atherosclerotic plaques of the carotid artery. CD163 gene expression correlated independently with (64)Cu-DOTATATE uptake measured by real-time quantitative polymerase chain reaction in the final multivariate model, indicating that (64)Cu-DOTATATE PET is detecting alternatively activated macrophages. This association could potentially improve noninvasive identification and characterization of vulnerable plaques.

Plasma neutrophil gelatinase-associated lipocalinin in the general population: association with inflammation and prognosis.

OBJECTIVE: Neutrophil gelatinase-associated lipocalin (NGAL) is a glycoprotein stored in granules of neutrophil leukocytes participating in inflammatory and atherosclerotic processes and possibly plaque rupture. Despite the putative role of NGAL in atherosclerosis and acute myocardial infarction, human studies of plasma NGAL are still limited. APPROACH AND RESULTS: We prospectively followed 5599 randomly selected men and women from the community in the fourth Copenhagen Heart Study. Plasma NGAL was measured at study entry. Participants were followed for 10 years. During follow-up, 20% died (n=1120) and 15% (n=884) developed a major adverse cardiovascular event. Plasma NGAL associated strongly with all inflammatory markers (high-sensitivity C-reactive protein, total leukocyte count, neutrophil count) and inversely with estimated glomerular filtration rate (all, P<0.001). Multivariate analysis identified neutrophil leukocyte count as the main determinant of plasma NGAL. During follow-up, participants with increasing NGAL had increased risk of all-cause mortality and major adverse cardiovascular event (both, P<0.001). Even after adjustment for confounding risk factors by Cox regression analysis, NGAL remained an independent predictor of both all-cause mortality and major adverse cardiovascular event. When added to the Framingham risk score, NGAL improved c-statistics and correctly reclassified ≈15% into more appropriate risk groups. In comparison with high-sensitivity C-reactive protein, when both markers were added to the Framingham risk score, NGAL conferred 3× to 4× the risk. CONCLUSIONS: Plasma NGAL is strongly associated with inflammation in the general population. NGAL independently associated with 10-year outcome, and when added to the Framingham risk score, NGAL both improves c-statistics and correctly reclassifies participants into more accurate risk categories.

Association between cardiac time intervals and incident heart failure after acute coronary syndrome.

BACKGROUND: Cardiac time intervals are sensitive markers of myocardial dysfunction that predispose to heart failure (HF). We aimed to investigate the association between cardiac time intervals and HF in patients with acute coronary syndrome (ACS). METHODS: This study included 386 ACS patients treated with percutaneous coronary intervention (PCI). Patients underwent an echocardiography examination a median of two days after PCI. Cardiac time intervals including isovolumic relaxation time (IVRT), isovolumic contraction time (IVCT), and systolic ejection time (ET), and myocardial performance index (MPI) were obtained by tissue Doppler echocardiography. The outcome was incident HF. RESULTS: During follow-up (median 4.3, IQR:1.0-6.7 years), 140 (36%) developed HF. In unadjusted analyses, IVRT was not associated with HF (HR 1.02 (0.95-1.10), p = 0.61, per 10ms increase), and neither was IVCT (HR 0.07 (0.95-1.22), p = 0.26, per 10ms increase). Increasing MPI was associated with a higher risk of HF (HR 1.20 (1.08-1.34), P = 0.001, per 0.1 increase), and so was decreasing ET (HR 1.13 (1.07-1.18), P < 0.001 per 10ms decrease). After multivariable adjustment for cardiovascular risk factors, MPI (HR 1.13 (1.01-1.27), P = 0.034) and ET (HR 1.09 (1.01-1.17), P = 0.025) remained significantly associated with incident HF. LVEF modified the association between ET and HF (p for interaction = 0.002), such that ET was associated with HF in patients with LVEF ≥ 36% (HR = 1.15 (1.06-1.24), P = 0.001, per 10ms decrease). CONCLUSION: In patients admitted with ACS, shortened ET and higher MPI were independently associated with an increased risk of incident HF. Additionally, ET was associated with incident HF in patients with LVEF above 36%.

Ratio of early transmitral inflow velocity to early diastolic strain rate predicts atrial fibrillation following acute myocardial infarction.

The ratio of early transmitral filling velocity to early diastolic strain rate (E/SRe) has been proposed as a new non-invasive measurement of left ventricular filling pressure. We aimed to investigate the ability of E/SRe to predict atrial fibrillation (AF) after ST-elevation myocardial infarction (STEMI). This was a prospective cohort study of patients (n = 369) with STEMI. Patients underwent an echocardiographic examination a median of two days after pPCI. By echocardiography, transmitral early filling velocity (E) was measured by pulsed-wave Doppler, and early diastolic strain rate (SRe) was measured by speckle tracking of the left ventricle. E was indexed to SRe and the early myocardial relaxation velocity (e') to obtain the E/SRe and E/e', respectively. The endpoint was new-onset AF. During follow-up (median 5.6 years, IQR: 5.0-6.1 years), 23 (6%) of the 369 patients developed AF. In unadjusted analyses, both E/SRe and E/e' were significantly associated with AF [E/SRe: HR = 1.06; (1.03-1.10); p < 0.001, per 10 increase] and [E/e': HR = 1.11 (1.05-1.17); p < 0.001, per 1 increase] and had equal Harrell's C-statistic of 0.71. However, only E/SRe remained an independent predictor after multivariable adjustments for clinical and echocardiographic parameters [E/SRe: HR = 1.06 (1.00-1.11); p = 0.044, per 10 increase]. E/SRe was further significantly associated with AF in patients with E/e' < 14 HR = 1.09 (1.01-1.17); p = 0.030, per 10 increase), also after multivariable adjustments. E/SRe is an independent predictor of AF in STEMI patients, even in subjects with seemingly normal filling pressure.

Acute myocardial infarction is associated with endothelial glycocalyx and cell damage and a parallel increase in circulating catecholamines.

INTRODUCTION: Excessive sympathoadrenal activation in critical illness contributes directly to organ damage, and high concentrations of catecholamines damage the vascular endothelium. This study investigated associations between potential drivers of sympathoadrenal activation, circulating catecholamines and biomarkers of endothelial damage and outcome in ST segment elevation myocardial infarction (STEMI)-patients, hypothesizing that the catecholamine surge would reflect shock degree and correlate with biomarkers of endothelial damage. METHODS: This was a prospective study of 678 consecutive STEMI-patients admitted to a single high-volume invasive heart centre for primary percutaneous coronary intervention (pPCI) from September 2006 to July 2008. Blood samples were drawn immediately before pPCI. Plasma adrenaline, noradrenaline, syndecan-1 and thrombomodulin were measured retrospectively with complete data in 571 patients (84%). Median follow-up time was 28 (IQR 23 to 34) months. Follow-up was 99.7% complete. Outcomes were all-cause and cardiovascular mortality, re-myocardial infarction and admission due to heart failure. RESULTS: Circulating noradrenaline and adrenaline correlated weakly but independently with syndecan-1 (rho = 0.15 and rho = 0.13, both P <0.01) and thrombomodulin (rho = 0.11 and rho = 0.17, both P <0.01), biomarkers of glycocalyx and endothelial cell damage, respectively. Considering biomarkers, patients with shock pre-pPCI had higher adrenaline and syndecan-1 and patients admitted to ICU post-pPCI had higher syndecan-1 (all P <0.05), and in the patients with shock (n = 51) catecholamines correlated strongly with thrombomodulin and syndecan-1 (rho = 0.31 to 0.42, all P <0.05). During follow-up, 78 (14%) patients died (37 cardiovascular deaths) and 65 (11%) were admitted with heart failure. By multivariate Cox proportional hazards analyses, one quartile higher plasma adrenaline was weakly but independently associated with both 30-day and long term mortality and heart failure (30-day all-cause mortality hazard ratio (95% CI) 1.39 (1.01 to 1.92), P = 0.046; 30-day heart failure 1.65 (1.17 to 2.34), P = 0.005; and long-term cardiovascular mortality 1.49 (1.08 to 2.04), P = 0.014). Furthermore, one quartile higher syndecan-1 was also weakly but independently associated with long-term all cause mortality (1.26 (1.02 to 1.57), P = 0.034). CONCLUSIONS: In STEMI patients treated with pPCI, catecholamines correlated weakly with biomarkers of endothelial damage, with the strongest correlations and highest adrenaline and syndecan-1 levels in patients with shock. Furthermore, adrenaline and syndecan-1 were weakly but independently associated with mortality and heart failure. Acute myocardial infarction appears to cause significant endothelial cell and glycocalyx injury and a parallel increase in circulating catecholamines.

Imaging of atherosclerosis with [64Cu]Cu-DOTA-TATE in a translational head-to-head comparison study with [18F]FDG, and Na[18F]F in rabbits.

Atherosclerosis is a chronic inflammatory disease of the larger arteries that may lead to cardiovascular events. Identification of patients at highest risk of cardiovascular events is challenging, but molecular imaging using positron emission tomography (PET) may prove useful. The aim of this study was to evaluate and compare head-to-head three different PET tracers. Furthermore, tracer uptake is compared to gene expression alterations of the arterial vessel wall. Male New Zealand White rabbits (control group; n = 10, atherosclerotic group; n = 11) were used for the study. Vessel wall uptake was assessed with the three different PET tracers: [18F]FDG (inflammation), Na[18F]F (microcalcification), and [64Cu]Cu-DOTA-TATE (macrophages), using PET/computed tomography (CT). Tracer uptake was measured as standardized uptake value (SUV), and arteries from both groups were analyzed ex vivo by autoradiography, qPCR, histology, and immunohistochemistry. In rabbits, the atherosclerotic group showed significantly higher uptake of all three tracers compared to the control group [18F]FDG: SUVmean 1.50 ± 0.11 versus 1.23 ± 0.09, p = 0.025; Na[18F]F: SUVmean 1.54 ± 0.06 versus 1.18 ± 0.10, p = 0.006; and [64Cu]Cu-DOTA-TATE: SUVmean 2.30 ± 0.27 versus 1.65 ± 0.16; p = 0.047. Of the 102 genes analyzed, 52 were differentially expressed in the atherosclerotic group compared to the control group and several genes correlated with tracer uptake. In conclusion, we demonstrated the diagnostic value of [64Cu]Cu-DOTA-TATE and Na[18F]F for identifying atherosclerosis in rabbits. The two PET tracers provided information distinct from that obtained with [18F]FDG. None of the three tracers correlated significantly to each other, but [64Cu]Cu-DOTA-TATE and Na[18F]F uptake both correlated with markers of inflammation. [64Cu]Cu-DOTA-TATE was higher in atherosclerotic rabbits compared to [18F]FDG and Na[18F]F.

Left atrial reservoir strain predicts ischaemic stroke after coronary artery bypass grafting independent of postoperative atrial fibrillation.

Aims: Measures of left atrial (LA) function are known to predict both ischaemic stroke and atrial fibrillation in specific patient groups. The aim of this study was to investigate the value of LA reservoir strain for predicting ischaemic stroke in patients undergoing coronary artery bypass grafting (CABG) and investigate whether the presence of postoperative atrial fibrillation (POAF) modified this relationship. Methods and results: Patients undergoing isolated CABG were included. The primary endpoint was ischaemic stroke. The association between LA reservoir strain and ischaemic stroke was investigated in uni- and multivariable Cox proportional hazards regression models including adjustment for POAF.We included 542 patients (mean age 67.3±8.9 years, 16.4% female). During a median follow-up period of 3.9 years, 21 patients (3.9%) experienced an ischaemic stroke. In total, 96 patients (17.7%) developed POAF during the index hospitalization. In a multivariable-adjusted Cox proportional hazards regression model, LA reservoir strain was significantly associated with the development of ischaemic stroke [HR (hazard ratio) 1.09 (95% CI 1.02-1.17) per 1% decrease, P = 0.011]. The presence of POAF did not modify this association (p for interaction = 0.07). The predictive value of the LA reservoir strain persisted in multiple sensitivity analyses including restricting the analysis to patients with normal left atrial volumes (LAV<34 ml/m2), patients without POAF, patients without prior stroke, and when excluding patients who developed atrial fibrillation at any time during follow-up. Conclusion: LA reservoir strain was independently associated with ischaemic stroke in CABG patients. The predictive value of LA reservoir strain was unaffected by the presence of POAF. Prospective studies are warranted to validate the potential usefulness of LA reservoir strain to predict postoperative ischaemic stroke in the setting of CABG.

Soluble form of membrane attack complex independently predicts mortality and cardiovascular events in patients with ST-elevation myocardial infarction treated with primary percutaneous coronary intervention.

BACKGROUND: The complement system is an important mediator of inflammation, which plays a pivotal role in atherosclerosis and acute myocardial infarction (AMI). Animal studies suggest that activation of the complement cascade resulting in the formation of soluble membrane attack complex (sMAC), contributes to both atherosclerosis and plaque rupture and may be the direct cause of tissue damage related to ischemia/reperfusion injury. However clinical data of sMAC during an AMI is sparse. Accordingly the aim was to investigate the prognostic role of sMAC in patients with ST-segment elevation myocardial infarction (STEMI). METHODS: We included 725 STEMI-patients admitted to a single, high-volume invasive heart centre, treated with primary percutaneous coronary intervention (PCI), from September 2006 to December 2008. Blood samples were drawn immediately before PCI. Plasma sMAC was measured using an in-house immunoassay. Endpoints were all-cause mortality (n = 62) and the combined endpoint (n = 122) of major cardiovascular events (MACE) defined as cardiovascular mortality and admission due recurrent AMI or heart failure. Follow-up time was 12 months. RESULTS: During 12 months of follow-up 62 patients died from all causes and 122 patients reached the combined end-point of MACE. Patients with high sMAC (>75th percentile) had increased risk of both all-cause mortality and MACE. Even after adjustment for confounding risk factors by Cox-regression analyses, high levels of sMAC remained an independent predictor of all-cause mortality (hazard ratio 1.81 [95% CI 1.06-3.06; P = .029]) and MACE (hazard ratio 1.70 [95% CI 1.16-2.48; P = .006]). CONCLUSIONS: High plasma sMAC independently predicts all-cause mortality and MACE in STEMI-patients treated with PCI.

Prognostic significance of electrocardiographic Q-waves in a low-risk population.

AIMS: In individuals without known heart disease, electrocardiographic Q-waves predict a poor prognosis. We aimed to examine whether prognostic information can be derived from the size and location of Q-waves in persons from the general population without known ischaemic heart disease (IHD) or heart failure (HF). METHODS AND RESULTS: Electrocardiograms (ECGs) of 5381 persons without known IHD or HF from the 4th Copenhagen City Heart Study were reviewed and Q-waves were classified according to their size and location. Multivariate Cox proportional hazards regression models were used to examine the associations of Q-waves adjusted for age, hypertension, diabetes, and estimated glomerular filtration rate with the risk of the combined endpoint of death and hospitalization for IHD. During a median of 7.8 years of follow-up, 1003 persons reached the combined endpoint. One hundred and fourteen (2.1%) had pathological Q-waves, of whom 44% suffered from an event compared with 18% from the control group, P< 0.001. Persons with hypertension, diabetes, and impaired renal function were more likely to have Q-waves. Even small Q-waves (i.e. Minnesota code 1.2.x-1.3.x) were associated with a poor prognosis, hazard ratio (HR) 1.4 [95% confidence interval (CI): 1.0-2.0; P< 0.05], though not as grave as large Q-waves (i.e. Minnesota code 1.1.x) HR 2.8 (95%CI: 1.6-5.0; P< 0.001). Conversely, there was no difference in the outcome of patients with anteriorly HR 1.6 (95%CI: 1.1-2.4) vs. posteriorly HR 1.5 (95%CI: 0.9-2.4) located Q-waves (P= 0.85). CONCLUSION: In the general population without known IHD or HF, even small Q-waves in the ECG are associated with a poor prognosis.

High-degree atrioventricular block complicating ST-segment elevation myocardial infarction in the era of primary percutaneous coronary intervention.

AIMS: Primary percutaneous coronary intervention (pPCI) has replaced thrombolysis as treatment-of-choice for ST-segment elevation myocardial infarction (STEMI). However, the incidence and prognostic significance of high-degree atrioventricular block (HAVB) in STEMI patients in the pPCI era has been only sparsely investigated. The objective of this study was to assess the incidence, predictors and prognostic significance of HAVB in STEMI patients treated with pPCI. METHODS AND RESULTS: This study included 2073 STEMI patients treated with pPCI. The patients were identified through a hospital register and the Danish National Patient Register. Both registers were also used to establish the diagnosis of HAVB. All-cause mortality was the primary endpoint. During a median follow-up of 2.9 years [interquartile range (IQR) 1.8-4.0] 266 patients died. High-degree atrioventricular block was documented in 67 (3.2%) patients of whom 25 died. Significant independent predictors of HAVB included right coronary artery occlusion, age >65 years, female gender, hypertension, and diabetes. The adjusted mortality rate was significantly increased in patients with HAVB compared to patients without HAVB [hazard ratio = 3.14 (95% confidence interval 2.04-4.84), P< 0.001]. A landmark-analysis 30 days post-STEMI showed equal mortality rates in the two groups. CONCLUSION: The incidence of HAVB in STEMI patients treated with pPCI has been reduced compared with reports from the thrombolytic era. However, despite this improvement high-degree AV block remains a severe prognostic marker in the pPCI era. The mortality rate was only increased within the first 30 days. High-degree atrioventricular block patients who survived beyond this time-point thus had a prognosis equal to patients without HAVB.

Osteoprotegerin predicts long-term outcome in patients with ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention.

BACKGROUND: Osteoprotegerin (OPG) is a glycoprotein with a regulatory role in immune, skeletal and vascular systems. Data suggest that high circulating OPG levels are associated with an increased risk of cardiovascular disease. We analyzed the association between OPG and long-term outcome in patients with ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (pPCI). METHODS: We included 716 consecutive STEMI patients admitted to a single high-volume invasive heart center from September 2006 to December 2008. Endpoints were all-cause mortality, repeat myocardial infarction, admission due to heart failure and combinations thereof. Median follow-up lasted 27 months (interquartile range: 22-33). RESULTS: OPG levels exhibited a non-Gaussian distribution and were therefore divided into quartiles. High levels of OPG were significantly associated with a worse outcome. After adjustment for conventional risk factors (e.g. C-reactive protein, estimated glomerular filtration rate, symptom-to-balloon time and troponin I) using Cox regression, OPG remained a significantly independent predictor of death (HR per increase in OPG quartile: 1.28; CI: 1.03-1.59; p = 0.03), repeat myocardial infarction (HR: 1.30; CI: 1.00-1.68; p = 0.05) and admission with heart failure (HR: 1.50; CI: 1.18-1.90; p = 0.001). CONCLUSION: This study shows that OPG independently predicts long-term outcome in STEMI patients treated with pPCI. Eventually, this knowledge could improve risk stratification and overall outcome.

Right ventricular strain predicts adverse outcomes in patients undergoing coronary artery bypass grafting.

Patients undergoing coronary artery bypass grafting (CABG) face an elevated risk of heart failure (HF) and cardiovascular (CV) death. Detailed myocardial tissue analyses of the right ventricle are now possible and may hold prognostic value in these patients. Accordingly, we aimed to evaluate the usefulness of right ventricular (RV) layer-specific RV free wall strain (RVFWS) for predicting HF and/or CV death. Patients undergoing CABG at Gentofte Hospital from 2006 to 2011 with a preoperative echocardiogram underwent RVWFS analysis. RVFWS was obtained by speckle tracking. The outcome was defined as a composite of HF and/or CV death. Cox proportional hazards regression, Harrell's C-statistics, and competing risk regression were used to assess the prognostic value of RVFWS. Of 317 patients, 30 (9.5%) reached the endpoint at a median follow-up of 3.5 years. The mean age was 67 years, 83% were men, and the mean LVEF was 50%. In univariable analyses, endo-RVFWS (HR 1.08, P < 0.001), mid-RVFWS (HR 1.07, P = 0.002), and epi-RVFWS (HR 1.07, P = 0.004, per 1% absolute decrease) were associated with a higher risk of HF or/and CV death. Furthermore, all three layers remained independently associated with the outcome after multivariable adjustment for baseline clinical and echocardiographic measurements. Low endo-RVFWS was associated with a more than threefold increased risk of the outcome (HR = 3.04 (1.45-6.38) P = 0.003). The same was observed for mid-RVFWS (HR = 3.16 (1.45-6.91) P = 0.004), and epi-RVFWS (HR = 3.00 (1.46-6.17) P = 0.003). In patients undergoing CABG, RVFWS assessed by speckle-tracking is a predictor of adverse outcomes.

Predictive value of left atrial strain in relation to atrial fibrillation following acute myocardial infarction.

BACKGROUND: Atrial fibrillation (AF) is the most common arrythmia following ST-segment elevation myocardial infarction (STEMI) and can lead to stroke and other heart-related diseases. This study aimed to determine the prognostic value of left atrial (LA) strain, obtained by speckle tracking echocardiography (STE), in predicting incident AF outcomes following STEMI treated with primary percutaneous coronary intervention (pPCI). METHODS AND RESULTS: This prospective study comprised of 392 STEMI patients treated with pPCI. The patients had an echocardiography performed at a median of two days after their STEMI. Along with conventional measures, LA strain was obtained by speckle tracking from two apical projections. The outcome was new-onset atrial fibrillation. LA reservoir, contractile and conduit strain were measurable from echocardiograms of 303 included patients. At a median follow-up time of 5.6 years (IQR: 5.0-6.1 years), 18 patients (6,3%) developed incident AF. Mean age was 62.0 years ±11.5 and follow-up was 100%. Significantly lower LA strain values were observed in patients who experienced AF during follow-up as compared to patients who didn't. Both reservoir, contractile and conduit strain were significant univariable predictors. In the multivariable model, only LA reservoir strain remained a significant independent predictor of AF. CONCLUSION: Left atrial reservoir strain obtained by two-dimensional speckle tracking echocardiography is an independent predictor of incident AF following STEMI.