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.

Prediction of obstructive coronary artery disease and prognosis in patients with suspected stable angina.

AIMS: We hypothesized that the modified Diamond-Forrester (D-F) prediction model overestimates probability of coronary artery disease (CAD). The aim of this study was to update the prediction model based on pre-test information and assess the model's performance in predicting prognosis in an unselected, contemporary population suspected of angina. METHODS AND RESULTS: We included 3903 consecutive patients free of CAD and heart failure and suspected of angina, who were referred to a single centre for assessment in 2012-15. Obstructive CAD was defined from invasive angiography as lesion requiring revascularization, >70% stenosis or fractional flow reserve <0.8. Patients were followed (mean follow-up 33 months) for myocardial infarction, unstable angina, heart failure, stroke, and death. The updated D-F prediction model overestimated probability considerably: mean pre-test probability was 31.4%, while only 274 (7%) were diagnosed with obstructive CAD. A basic prediction model with age, gender, and symptoms demonstrated good discrimination with C-statistics of 0.86 (95% CI 0.84-0.88), while a clinical prediction model adding diabetes, family history, and dyslipidaemia slightly improved the C-statistic to 0.88 (0.86-0.90) (P for difference between models <0.0001). Quartiles of probability of CAD from the clinical prediction model provided good diagnostic and prognostic stratification: in the lowest quartiles there were no cases of obstructive CAD and cumulative risk of the composite endpoint was less than 3% at 2 years. CONCLUSION: The pre-test probability model recommended in current ESC guidelines substantially overestimates likelihood of CAD when applied to a contemporary, unselected, all-comer population. We provide an updated prediction model that identifies subgroups with low likelihood of obstructive CAD and good prognosis in which non-invasive testing may safely be deferred.

Echocardiography improves prediction of major adverse cardiovascular events in a population with type 1 diabetes and without known heart disease: the Thousand & 1 Study.

AIMS/HYPOTHESIS: Cardiovascular disease is the most common comorbidity in type 1 diabetes. However, current guidelines do not include routine assessment of myocardial function. We investigated whether echocardiography provides incremental prognostic information in individuals with type 1 diabetes without known heart disease. METHODS: A prospective cohort of individuals with type 1 diabetes without known heart disease was recruited from the outpatient clinic. Follow-up was performed through Danish national registers. The association of echocardiography with major adverse cardiovascular events (MACE) and the incremental prognostic value when added to the clinical Steno T1D Risk Engine were examined. RESULTS: A total of 1093 individuals were included: median (interquartile range) age 50.2 (39.2-60.3) years and HbA1c 65 (56-74) mmol/mol; 53% men; and mean (SD) BMI 25.5 (3.9) kg/m2 and diabetes duration 25.8 (14.6) years. During 7.5 years of follow-up, 145 (13.3%) experienced MACE. Echocardiography significantly and independently predicted MACE: left ventricular ejection fraction (LVEF) <45% (n = 18) vs ≥45% (n = 1075), HR (95% CI) 3.93 (1.91, 8.08), p < 0.001; impaired global longitudinal strain (GLS), 1.65 (1.17, 2.34) (n = 263), p = 0.005; diastolic mitral early velocity (E)/early diastolic tissue Doppler velocity (e') <8 (n = 723) vs E/e' 8-12 (n = 285), 1.59 (1.04, 2.42), p = 0.031; and E/e' <8 vs E/e' ≥12 (n = 85), 2.30 (1.33, 3.97), p = 0.003. In individuals with preserved LVEF (n = 1075), estimates for impaired GLS were 1.49 (1.04, 2.15), p = 0.032; E/e' <8 vs E/e' 8-12, 1.61 (1.04, 2.49), p = 0.033; and E/e' <8 vs E/e' ≥12, 2.49 (1.41, 4.37), p = 0.001. Adding echocardiographic variables to the Steno T1D Risk Engine significantly improved risk prediction: Harrell's C statistic, 0.791 (0.757, 0.824) vs 0.780 (0.746, 0.815), p = 0.027; and net reclassification index, 52%, p < 0.001. CONCLUSIONS/INTERPRETATION: In individuals with type 1 diabetes without known heart disease, echocardiography significantly improves risk prediction over and above guideline-recommended clinical risk factors alone and could have a role in clinical care.

Early Versus Standard Care Invasive Examination and Treatment of Patients With Non-ST-Segment Elevation Acute Coronary Syndrome.

BACKGROUND: The optimal timing of invasive coronary angiography (ICA) and revascularization in patients with non-ST-segment elevation acute coronary syndrome is not well defined. We tested the hypothesis that a strategy of very early ICA and possible revascularization within 12 hours of diagnosis is superior to an invasive strategy performed within 48 to 72 hours in terms of clinical outcomes. METHODS: Patients admitted with clinical suspicion of non-ST-segment elevation acute coronary syndrome in the Capital Region of Copenhagen, Denmark, were screened for inclusion in the VERDICT trial (Very Early Versus Deferred Invasive Evaluation Using Computerized Tomography) ( ClinicalTrials.gov NCT02061891). Patients with ECG changes indicating new ischemia or elevated troponin, in whom ICA was clinically indicated and deemed logistically feasible within 12 hours, were randomized 1:1 to ICA within 12 hours or standard invasive care within 48 to 72 hours. The primary end point was a combination of all-cause death, nonfatal recurrent myocardial infarction, hospital admission for refractory myocardial ischemia, or hospital admission for heart failure. RESULTS: A total of 2147 patients were randomized; 1075 patients allocated to very early invasive evaluation had ICA performed at a median of 4.7 hours after randomization, whereas 1072 patients assigned to standard invasive care had ICA performed 61.6 hours after randomization. Among patients with significant coronary artery disease identified by ICA, coronary revascularization was performed in 88.4% (very early ICA) and 83.1% (standard invasive care). Within a median follow-up time of 4.3 (interquartile range, 4.1-4.4) years, the primary end point occurred in 296 (27.5%) of participants in the very early ICA group and 316 (29.5%) in the standard care group (hazard ratio, 0.92; 95% CI, 0.78-1.08). Among patients with a GRACE risk score (Global Registry of Acute Coronary Events) >140, a very early invasive treatment strategy improved the primary outcome compared with the standard invasive treatment (hazard ratio, 0.81; 95% CI, 0.67-1.01; P value for interaction=0.023). CONCLUSIONS: A strategy of very early invasive coronary evaluation does not improve overall long-term clinical outcome compared with an invasive strategy conducted within 2 to 3 days in patients with non-ST-segment elevation acute coronary syndrome. However, in patients with the highest risk, very early invasive therapy improves long-term outcomes. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02061891.

Do ultrathin strut bare-metal stents with passive coating improve efficacy in large coronary arteries? Insights from the randomized, multicenter BASKET-PROVE trials.

BACKGROUND: The new generation thinner-strut silicon carbide (SiC) coated cobalt chromium (CoCr) bare-metal stents (BMS) are designed to accelerate rapid endothelialisation and reduce thrombogenicity when implanted in coronary arteries. However, smaller studies suggest higher rates of symptomatic restenosis in patients receiving the newer generation BMS. We investigated the efficacy of a newer generation ultrathin strut silicon-carbide coated cobalt-chromium (CoCr) BMS (SCC-BMS) as compared to an older thin-strut uncoated CoCr BMS (UC-BMS) in patients presenting with coronary artery disease requiring stenting of large vessels (≥3.0 mm). METHODS: All patients randomized to SCC- (n = 761) or UC-BMS (n = 765) in the two BASKET-PROVE trials were included. Design, patients, interventions and follow-up were similar between trials except differing regimens of dual antiplatelet therapy. The primary endpoint was clinically driven target-vessel revascularization within 24 months. Safety endpoints of cardiac death, non-fatal myocardial infarction (MI), and definite/probable stent thrombosis (ST) were also assessed. We used inverse probability weighted proportional hazards Cox regressions adjusting for known confounders. RESULTS: Demographics, clinical presentation, and risk factors were comparable between the groups, but patients receiving SCC-BMS underwent less complex procedures. The risk for clinically driven TVR was increased om the SCC-BMS group compared to the UC-BMS group (cumulative incidence, 10.6% vs. 8.4%; adjusted relative hazard [HR], 1.49 [95% CI, 1.05-2.10]). No differences in safety endpoints were detected, cardiac death (1.6% vs. 2.8%; HR, 0.62 [CI, 0.30-1.27]), non-fatal MI (3.2% vs. 2.5%; HR, 1.56 [CI, 0.83-2.91]), and definite/probable ST (0.8% vs. 1.1%; HR, 1.17 [CI, 0.39-3.50]). Differences in strut thickness between the two stents did not explain the association between stent type and clinically driven TVR. CONCLUSIONS: In patients requiring stenting of large coronary arteries, use of the newer generation SCC-BMS was associated with a higher risk of clinically driven repeat revascularization compared to the UC-BMS with no signs of an offsetting safety benefit.

Resting heart rate and mortality in the very old.

The number of very old individuals in the population is rapidly increasing. Previous studies have indicated that many factors known to be strongly associated with survival among middle-aged and elderly show no association among the oldest old. Resting heart rate (RHR) is associated with increased risk of death in the general population as well as in patients with various types of heart disease. The association between RHR and mortality in the very old is the subject of this report. The study population was identified in The Nationwide Danish 1905 Cohort Study (n = 1086) and comprised 854 subjects with a median age of 95.2 years (range 94.7-95.9), in whom RHR was measured by radial pulse palpation. Participants were followed until death through the civil registration system, and remaining lifespan after RHR measure was used as outcome. Participants were divided into six groups according to RHR (≤50, 51-60, 61-70, 71-80, 81-90 and ≥91) with the largest group used as the reference group (61-70 beats per minute (bpm)). Survival analyses using Cox' proportional hazards models were performed to study the association between RHR and mortality. Median RHR was 68 bpm in males (IQR 62-76) and 70 bpm (IQR 64-78) in females. After stratifying both sexes into six groups according to RHR, we found no significant difference in remaining lifespan between groups in either males or females. No significantly increased risk was demonstrated in groups with higher RHR. In very old people, elevated RHR is not associated with increased mortality.

Resting Heart Rate Is Not Associated with Cognitive Function.

AIMS: In order to examine the hypothesis that elevated resting heart rate (RHR) is associated with impaired cognitive score, we investigated the relationship between RHR and cognitive score in middle-aged, elderly and old Danish subjects from the general population. METHODS: Composite cognitive scores derived from the result of 5 age-sensitive cognitive tests for a total of 7,002 individuals (Middle-aged Danish twin: n = 4,132, elderly Danish twins: n = 2,104 and Danish nonagenarian: n = 766) divided according to RHR and compared using linear regression models adjusted for sex, age, previous heart conditions and hypertension. RHR was assessed by palpating radial pulse. Genetic and shared environmental confounding was addressed in intrapair analyses of 2,049 twin pairs. RESULTS: In unadjusted multivariate models and in multivariable models adjusting for age, sex, heart conditions and hypertension, RHR was not associated with cognitive function. Furthermore, the intrapair analyses showed that RHR was not associated with cognitive score testing within twin pairs, as measured by the proportion of twin pairs in which the twin with higher RHR also was the twin with the lowest composite cognitive score (1,049 pairs of 2,049 pairs [51% (95% CI 49-53), p < 0.289]). CONCLUSION: While elevated RHR has been shown to be associated with adverse health events and poor fitness level, RHR has no relation to cognitive function in the general population.

Second generation drug-eluting stents versus bare-metal stents for percutaneous coronary intervention of the proximal left anterior descending artery: An analysis of the BASKET-PROVE I and II trials.

OBJECTIVES: To compare mid-term outcomes between patients undergoing proximal left anterior descending artery (LAD) percutaneous coronary intervention (PCI) with second generation drug-eluting stent (DES) or bare-metal stent (BMS). BACKGROUND: PCI with BMS and first-generation DES have shown to be safe options for the treatment of proximal LAD stenosis, however associated with considerable reintervention rates. Overall, second-generation DES has proven to be superior to BMS and first-generation DES, nevertheless, its effect for proximal LAD PCI has not previously been reported. METHODS: We analyzed 2-year outcomes of 1,100 patients from the BASKET-PROVE I and II trials, referred for proximal LAD PCI with second generation DES (n = 680) or BMS (n = 420). RESULTS: The cumulative 2-year incidence of major adverse cardiac events (MACE, composite of cardiac death, myocardial infarction (MI) and target vessel revascularization (TVR)) was lower in second generation DES than in BMS treated patients (7.3% vs. 12.3%; HR 0.57, 95% CI 0.39/0.85), mainly driven by a reduced rate of TVR (3.7% vs. 10.0%; HR 0.35, CI 0.21/0.58). No difference was found in cardiac death (1.9% vs. 1.9%; HR 1.01, CI 0.42/2.44) and MI (4.4% vs. 4.7%; HR 0.93, CI 0.53/1.64). The benefit of DES use seemed to be more prominent in female patients with a reduction in MACE (P for interaction = 0.025). CONCLUSIONS: In patients with proximal LAD stenosis, treatment with second-generation DES was associated with reduced 2-year rates of adverse cardiac events and TVR compared to BMS, with reintervention rates similar to those earlier reported from bypass surgery.

Cholesterol remnants and triglycerides are associated with decreased myocardial function in patients with type 2 diabetes.

BACKGROUND: Recently, genetic studies have suggested a causal relationship between cholesterol remnants and ischemic heart disease. We aimed to determine whether cholesterol remnants and its marker, triglyceride levels, are associated with cardiac function as determined by sensitive echocardiographic measures in a population of patients with type 2 diabetes. METHODS: Comprehensive echocardiography including 2D-speckle tracking echocardiography was performed on a representative sample of 924 patients with type 2 diabetes-730 of whom were treated with statins. These were recruited from two large secondary care centers. RESULTS: In multivariable analyses, triglycerides and cholesterol remnants were not associated with left ventricular ejection fraction, but with subtle measures of systolic function, including global longitudinal strain by speckle tracking and longitudinal displacement by tissue Doppler echocardiography: global longitudinal strain [0.33 % (0.14), p = 0.02 per doubling in cholesterol remnants and 0.28 % (0.13), p = 0.03 per doubling in triglyceride levels] and with longitudinal displacement [-0.25 mm (0.10), p = 0.01 per doubling in cholesterol remnants and -0.25 mm (0.09), p = 0.005 per doubling in triglyceride levels]. Subgroup analyses of patients receiving statin therapy and patients without known heart disease revealed similar results, but the association was not present in patients with known heart disease. CONCLUSION: In patients with type 2 diabetes, subtle decrease in left ventricular function is present with increasing levels of cholesterol remnants and triglyceride levels indicating an effect of these on cardiac function that is not detectable by conventional echocardiography.

Use of diagnostic coronary angiography in women and men presenting with acute myocardial infarction: a matched cohort study.

BACKGROUND: Based on evident sex-related differences in the invasive management of patients presenting with acute myocardial infarction (AMI), we sought to identify predictors of diagnostic coronary angiography (DCA) and to investigate reasons for opting out an invasive strategy in women and men. METHODS: The study was designed as a matched cohort study. We randomly selected 250 female cases from a source population of 4000 patients hospitalized with a first AMI in a geographically confined region of Denmark from January 2010 to November 2011. Each case was matched to a male control on age and availability of cardiac invasive facilities at the index hospital. We systematically reviewed medical records for risk factors, comorbid conditions, clinical presentation, and receipt of DCA. Clinical justifications, as stated by the treating physician, were noted for the subset of patients who did not receive a DCA. RESULTS: Overall, 187 women and 198 men received DCA within 60 days (75 % vs. 79 %, hazard ratio: 0.82 [0.67-1.00], p = 0.047).In the subset of patients who did not receive a DCA (n = 114), clinical justifications for opting out an invasive strategy was not documented for 21 patients (18.4 %). Type 2 myocardial infarction was noted in 11 patients (women versus men; 14.5 % vs. 3.8 %, p = 0.06) and identified as a potential confounder of the sex-DCA relationship. Receipt of DCA was predicted by traditional risk factors for ischaemic heart disease (family history of cardiovascular disease, hypercholesterolemia, and smoking) and clinical presentation (chest pain, ST-segment elevations). Although prevalent in both women and men, the presence of relative contraindications did not prohibit the use of DCA. CONCLUSION: In this matched cohort of patients with a first AMI, women and men had different clinical presentations despite similar age. However, no differences in the distribution of relative contraindications for DCA were found between the sexes. Type 2 MI posed a potentiel confounder for the sex-related differences in the use of DCA. Importantly,clinical justification for opting out an invasive strategy was not documented in almost one fifth of patients not receiving a DCA.

Effectiveness of an early versus a conservative invasive treatment strategy in acute coronary syndromes: a nationwide cohort study.

BACKGROUND: Randomized clinical trials have found that early invasive strategies reduce mortality, myocardial infarction (MI), and rehospitalization compared with a conservative invasive approach in acute coronary syndromes (ACSs), but the effectiveness of such strategies in real-world settings is unknown. OBJECTIVE: To investigate adverse cardiovascular outcomes of an early versus a conservative invasive strategy in a national cohort of patients with ACSs. DESIGN: Retrospective cohort study. SETTING: Administrative health care data on hospitalizations, procedures, and outcomes abstracted from the Danish national registries and covering all acute invasive procedures in patients presenting with an ACS. PATIENTS: 19 704 propensity score-matched patients hospitalized with a first ACS between 1 January 2005 and 31 December 2011. MEASUREMENTS: Risk for cardiac death or rehospitalization for MI within 60 days of hospitalization. RESULTS: Compared with a conservative approach, early invasive strategies were associated with a lower risk for cardiac death (cumulative incidence, 5.9% vs. 7.6%; adjusted hazard ratio [HR], 0.75 [95% CI, 0.66 to 0.84]; P < 0.001). Similar results were found for rehospitalization for MI (cumulative incidence, 3.4% vs. 5.0%; adjusted odds ratio, 0.67 [CI, 0.58 to 0.77]; P < 0.001) and all-cause death (cumulative incidence, 7.3% vs. 10.6%; adjusted HR, 0.65 [CI, 0.59 to 0.72]; P < 0.001). LIMITATION: Potential residual confounding due to lack of core clinical variables. CONCLUSION: In this real-world cohort of patients with a first hospitalization for an ACS, the use of an early invasive treatment strategy was associated with a lower risk for cardiac death and rehospitalization for MI compared with a conservative invasive approach. PRIMARY FUNDING SOURCE: Department of Cardiology, University Hospital Gentofte.

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.

Prevalence of systolic and diastolic dysfunction in patients with type 1 diabetes without known heart disease: the Thousand & 1 Study.

AIMS/HYPOTHESIS: Heart failure is one of the leading causes of mortality in type 1 diabetes. Early identification is vitally important. We sought to determine the prevalence and clinical characteristics associated with subclinical impaired systolic and diastolic function in type 1 diabetes patients without known heart disease. METHODS: In this cross-sectional examination of 1,093 type 1 diabetes patients without known heart disease, randomly selected from the Steno Diabetes Center, complete clinical and echocardiographic examinations were performed and analysed in uni- and multivariable regression models. RESULTS: The mean (SD) age was 49.6 (15) years, 53% of participants were men, and the mean duration of diabetes was 25.5 (15) years. Overall, 15.5% (n = 169) of participants had grossly abnormal systolic or diastolic function, including 1.7% with left ventricular ejection fraction (LVEF) < 45% and 14.4% with evidence of long-standing diastolic dysfunction. In univariable models, clinical characteristics associated with abnormal myocardial function were: age (per 10 years), OR (95% CI) 2.1 (1.8, 2.4); diabetes duration (per 10 years), 1.7 (1.4, 1.9); systolic BP ≥ 140 mmHg, 2.7 (1.9, 3.8); diastolic BP ≥ 90 mmHg, 1.8 (1.0, 3.1); estimated (e)GFR < 60 ml min(-1) 1.73 m(-2), 3.8 (2.5, 5.9); microalbuminuria, 2.0 (1.3, 3.0); macroalbuminuria, 5.9 (3.8, 9.3); proliferative retinopathy, 3.6 (2.3, 5.8); blindness, 10.1 (3.2, 31.6); and peripheral neuropathy, 3.8 (2.7, 5.3). In multivariable models only age (2.1 [1.7, 2.5]), female sex, (1.9 [1.2, 2.8]) and macroalbuminuria (5.2 [2.9, 10.3]) remained significantly associated with subclinical grossly abnormal myocardial function. CONCLUSIONS/INTERPRETATION: Subclinical myocardial dysfunction is a common finding in type 1 diabetes patients without known heart disease. Type 1 diabetes patients with albuminuria are at greatly increased risk of having subclinical abnormal myocardial function compared with patients without albuminuria. Echocardiography may be particularly warranted in patients with albuminuria.

Safety and efficacy of drug-eluting stents in women: a patient-level pooled analysis of randomised trials.

BACKGROUND: The safety and efficacy of drug-eluting stents (DES) in the treatment of coronary artery disease have been assessed in several randomised trials. However, none of these trials were powered to assess the safety and efficacy of DES in women because only a small proportion of recruited participants were women. We therefore investigated the safety and efficacy of DES in female patients during long-term follow-up. METHODS: We pooled patient-level data for female participants from 26 randomised trials of DES and analysed outcomes according to stent type (bare-metal stents, early-generation DES, and newer-generation DES). The primary safety endpoint was a composite of death or myocardial infarction. The secondary safety endpoint was definite or probable stent thrombosis. The primary efficacy endpoint was target-lesion revascularisation. Analysis was by intention to treat. FINDINGS: Of 43,904 patients recruited in 26 trials of DES, 11,557 (26·3%) were women (mean age 67·1 years [SD 10·6]). 1108 (9·6%) women received bare-metal stents, 4171 (36·1%) early-generation DES, and 6278 (54·3%) newer-generation DES. At 3 years, estimated cumulative incidence of the composite of death or myocardial infarction occurred in 132 (12·8%) women in the bare-metal stent group, 421 (10·9%) in the early-generation DES group, and 496 (9·2%) in the newer-generation DES group (p=0·001). Definite or probable stent thrombosis occurred in 13 (1·3%), 79 (2·1%), and 66 (1·1%) women in the bare-metal stent, early-generation DES, and newer-generation DES groups, respectively (p=0·01). The use of DES was associated with a significant reduction in the 3 year rates of target-lesion revascularisation (197 [18·6%] women in the bare-metal stent group, 294 [7·8%] in the early-generation DES group, and 330 [6·3%] in the newer-generation DES group, p<0·0001). Results did not change after adjustment for baseline characteristics in the multivariable analysis. INTERPRETATION: The use of DES in women is more effective and safe than is use of bare-metal stents during long-term follow-up. Newer-generation DES are associated with an improved safety profile compared with early-generation DES, and should therefore be thought of as the standard of care for percutaneous coronary revascularisation in women. FUNDING: Women in Innovation Initiative of the Society of Cardiovascular Angiography and Interventions.

Agreement between public register and adjudication committee outcome in a cardiovascular randomized clinical trial.

UNLABELLED: The objective of this study is to describe the agreement between randomized trial outcome assessment by committee and outcomes entirely identified through public registers. METHODS: In the CLARICOR trial, 4,372 patients with stable coronary heart disease received a short course of clarithromycin versus placebo and were followed up for 2.6 years. The pertinent hospital records and death certificates had originally been evaluated by the adjudication committee using common definitions of outcomes mapped into a 6-category list. We now mechanically converted the International Classification of Diseases-coded diagnoses of the public registries into the same categories. After cross-tabulation of the committee diagnoses with National Patient Register diagnoses and Register of Causes of Death, we calculate agreement and compare the estimated intervention effects of the 2 data sets. RESULTS: With public register data, the protocol-specified categories were slightly more frequent. Overall agreement was 74% for hospital discharges and 60% for cause of death, but the intervention effect, expressed as a hazard ratio, stayed within 4% of the value originally obtained with the adjudication committee (P ≥ .35). CONCLUSIONS: Our results show a modest agreement between formal adjudication and outcomes deducible from public registers. However, the estimated intervention effect did not differ noticeably between the 2 data sources. If studies on a wide range of public registers confirm these findings, register outcomes may be considered as a replacement for adjudication committees.

Tradeoff between bleeding and stent thrombosis in different dual antiplatelet therapy regimes: Importance of case fatality rates and effective treatment durations.

BACKGROUND: The tradeoff between stent thrombosis (ST) and major bleeding (MB) of 12- versus 6-month dual antiplatelet therapy (DAPT) after coronary stent implantation has not been clearly defined. METHODS: Definite/probable ST and MB (TIMI major and Bleeding Academic Research Consortium (BARC) ≥ 3) were compared in 2 subsequent trials with similar inclusion criteria but different DAPT duration, that is, BASKET (6 months; n = 557) and BASKET-PROVE (12 months; n = 2,314), between months 0 to 6 (DAPT in both trials), 7 to 12 (DAPT in BASKET-PROVE only), and 13 to 24 (aspirin in both trials) using propensity score-adjusted, time-stratified Cox proportional hazard models. RESULTS: Overall, event rates were low with fewer ST but similar MB in prolonged DAPT. Analysis of the 3 periods showed a uniform pattern for ST (interaction DAPT/period; P = .145) but an inconsistent pattern for MB (interaction DAPT/period; P < .001 for TIMI major and P = .046 for BARC ≥ 3), with more MB occurring during months 7 to 12 with prolonged DAPT. Considering observed case fatality rates of 31% with ST and 11% with MB, the extrapolated prevention of 27 ST deaths and the excess of 5 MB deaths resulted in an expected benefit of 22 survivors/10,000 patients treated over 2 years with prolonged DAPT. CONCLUSION: Despite overall low event rates, prolonged DAPT was associated with more MB during months 7 to 12 according to the interaction DAPT/period. Given the higher observed case fatality rates of ST versus MB, 12- versus 6-month DAPT was associated with an extrapolated reduction in mortality. Effective treatment periods and case fatality rates seem important in the analysis of different DAPT durations, specifically with regard to ongoing trials.

Low cardiac output as physiological phenomenon in hibernating, free-ranging Scandinavian brown bears (Ursus arctos) - an observational study.

BACKGROUND: Despite 5-7 months of physical inactivity during hibernation, brown bears (Ursus arctos) are able to cope with physiological conditions that would be detrimental to humans. During hibernation, the tissue metabolic demands fall to 25% of the active state. Our objective was to assess cardiac function associated with metabolic depression in the hibernating vs. active states in free-ranging Scandinavian brown bears. METHODS: We performed echocardiography on seven free-ranging brown bears in Dalarna, Sweden, anesthetized with medetomidine-zolazepam-tiletamine-ketamine during winter hibernation in February 2013 and with medetomidine-zolazepam-tiletamine during active state in June 2013. We measured cardiac output noninvasively using estimates of hemodynamics obtained by pulsed wave Doppler echocardiography and 2D imaging. Comparisons were made using paired T-tests. RESULTS: During hibernation, all hemodynamic indices were significantly decreased (hibernating vs. active state): mean heart rate was 26.0 (standard deviation (SD): 5.6) beats per min vs. 75.0 (SD: 17.1) per min (P=0.002), mean stroke volume 32.3 (SD: 5.2) ml vs. 47.1 (SD: 7.9) ml (P=0.008), mean cardiac output 0.86 (SD: 0.31) l/min vs. 3.54 (SD: 1.04) l/min (P=0.003), and mean cardiac index 0.63 (SD: 0.21) l/min/kg vs. 2.45 (SD: 0.52) l/min/ m2 (P<0.001). Spontaneous echo contrast was present in all cardiac chambers in all seven bears during hibernation, despite the absence of atrial arrhythmias and valvular disease. CONCLUSION: Free-ranging brown bears demonstrate hemodynamics comparable to humans during active state, whereas during hibernation, we documented extremely low-flow hemodynamics. Understanding these physiological changes in bears may help to gain insight into the mechanisms of cardiogenic shock and heart failure in humans.

Symptoms of angina pectoris increase the probability of disability pension and premature exit from the workforce even in the absence of obstructive coronary artery disease.

AIMS: To evaluate probabilities of disability pension (DP) and premature exit from the workforce (PEW) in patients with stable angina symptoms and no obstructive coronary artery disease (CAD) at angiography compared with obstructive CAD and asymptomatic reference individuals. METHODS AND RESULTS: We followed 4303 patients with no prior cardiovascular disease having a first-time coronary angiography (CAG) in 1998-2009 due to stable angina symptoms and 2772 reference individuals from the Copenhagen City Heart Study, all aged <65 years, through registry linkage until 2009 for DP and PEW. Five-year age-adjusted DP-free survival probabilities for reference individuals, patients with angiographically normal coronary arteries, angiographically diffuse non-obstructive CAD, 1 stenotic coronary vessel (1VD), 2VD, and 3VD, respectively, were 0.96, 0.88, 0.84, 0.82, 0.85, and 0.78 in women and 0.98, 0.90, 0.89, 0.89, 0.88, and 0.87 in men. Significant predictors of DP were higher age, angina symptoms, higher body mass index, diabetes, smoking, job status, non-marital status in men, lower income, lower educational level, and co-morbidity. Compared with the reference population, probabilities of DP and PEW were significantly increased in all patients with no gender difference (P > 0.2 for interaction). Thus, in pooled multivariable-adjusted analysis, patients referred to CAG for angina had a three-fold higher probability of DP and ~50% higher probability of PEW, with little difference between patients with angiographically normal coronary arteries, angiographically diffuse non-obstructive CAD, 1VD, 2VD, 3VD, the hazard ratios for DP being 2.7, 3.0, 3.3, 3.1, and 3.2 (all P < 0.001) and for PEW being 1.3, 1.4, 1.5, 1.6, and 1.6 (all P < 0.05). CONCLUSION: Patients with angina symptoms and angiographically normal coronary arteries, diffuse non-obstructive CAD, or obstructive CAD at angiography have a three-fold increased probability of DP regardless of angiographic findings.

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.

Stable angina pectoris with no obstructive coronary artery disease is associated with increased risks of major adverse cardiovascular events.

AIMS: Patients with chest pain and no obstructive coronary artery disease (CAD) are considered at low risk for cardiovascular events but evidence supporting this is scarce. We investigated the prognostic implications of stable angina pectoris in relation to the presence and degree of CAD with no obstructive CAD in focus. METHODS AND RESULTS: We identified 11 223 patients referred for coronary angiography (CAG) in 1998-2009 with stable angina pectoris as indication and 5705 participants from the Copenhagen City Heart Study for comparison. Main outcome measures were major adverse cardiovascular events (MACE), defined as cardiovascular death, myocardial infarction, stroke or heart failure, and all-cause mortality. Significantly more women (65%) than men (32%) had no obstructive CAD (P< 0.001). In Cox's models adjusted for age, body mass index, diabetes, smoking, and use of lipid-lowering or antihypertensive medication, hazard ratios (HRs) associated with no obstructive CAD were similar in men and women. In the pooled analysis, the risk of MACE increased with increasing degrees of CAD with multivariable-adjusted HRs of 1.52 (95% confidence interval, 1.27-1.83) for patients with normal coronary arteries and 1.85 (1.51-2.28) for patients with diffuse non-obstructive CAD compared with the reference population. For all-cause mortality, normal coronary arteries and diffuse non-obstructive CAD were associated with HRs of 1.29 (1.07-1.56) and 1.52 (1.24-1.88), respectively. CONCLUSION: Patients with stable angina and normal coronary arteries or diffuse non-obstructive CAD have elevated risks of MACE and all-cause mortality compared with a reference population without ischaemic heart disease.