The chairpersons of the national working groups/societies of interventional cardiology in European countries and selected experts known to be involved in the national registries joined the writing group upon invitation. Data were collected about the country and any existing national STEMI or PCI registries, about STEMI epidemiology, and treatment in each given country and about PCI and p-PCI centres and procedures in each country. Results from the national and/or regional registries in 30 countries were included in this analysis. The annual incidence of hospital admission for any acute myocardial infarction (AMI) varied between 90–312/100 thousand/year, the incidence of STEMI alone ranging from 44 to 142. Primary PCI was the dominant reperfusion strategy in 16 countries and TL in 8 countries. The use of a p-PCI strategy varied between 5 and 92% (of all STEMI patients) and the use of TL between 0 and 55%. Any reperfusion treatment (p-PCI or TL) was used in 37–93% of STEMI patients. Significantly less reperfusion therapy was used in those countries where TL was the dominant strategy. The number of p-PCI procedures per million per year varied among countries between 20 and 970. The mean population served by a single p-PCI centre varied between 0.3 and 7.4 million inhabitants. In those countries offering p-PCI services to the majority of their STEMI patients, this population varied between 0.3 and 1.1 million per centre. In-hospital mortality of all consecutive STEMI patients varied between 4.2 and 13.5%, for patients treated by TL between 3.5 and 14% and for patients treated by p-PCI between 2.7 and 8%. The time reported from symptom onset to the first medical contact (FMC) varied between 60 and 210 min, FMC-needle time for TL between 30 and 110 min, and FMC-balloon time for p-PCI between 60 and 177 min.

Most North, West, and Central European countries used p-PCI for the majority of their STEMI patients. The lack of organized p-PCI networks was associated with fewer patients overall receiving some form of reperfusion therapy.

Left ventricular dyssynchrony assessments were performed in 100 NSTEMI patients followed-up for 1 year using a composite dyssynchrony score. Early LV dyssynchrony was independently predicted by the presence of significant proximal left circumflex artery (LCx) stenosis and global systolic dysfunction. Left ventricular end-diastolic volume index decreased with time and was independently determined by a lower number of diseased vessels and the absence of early dyssynchrony. Left ventricular end-systolic volume index decreased with time and was independently determined by the absence of early dyssynchrony, lower number of diseased vessels, and revascularization. Left ventricular ejection fraction increased with time and was independently determined by the absence of early dyssynchrony, lower number of diseased vessels, and revascularization. The composite dyssynchrony score was an independent determinant of a persistently dilated LV and low LVEF at follow-up.

After NSTEMI, proximal LCx stenosis and impaired LV function independently predicted LV dyssynchrony. The composite dyssynchrony score had prognostic value and identified patients with persistently dilated and impaired LV on follow-up.

We randomly assigned 193 patients with lesions carrying a high risk of restenosis to have the Genous stent or the Taxus stent implanted. Lesions were considered high risk of restenosis if one of the following applied: chronic total occlusion, lesion length >23 mm, vessel diameter <2.8 mm, or any lesion in a diabetic patient. At 1-year, the rate of the primary end point, target vessel failure (TVF), was 17.3% in the Genous stent group when compared with 10.5% in the Taxus stent group [risk difference (RD) 6.8%, 95% CI –3.1 to 16.7%], a difference predominantly due to a higher incidence of repeat revascularization in patients treated with the Genous stent. In contrast, no stent thrombosis was observed in the Genous stent group compared to 4 stent thromboses in the Taxus stent group (RD –4.2%; 95% CI –10.3 to 0.3%). Repeat angiography between 6 and 12 months in a subgroup of patients showed a significantly higher late loss in the Genous stent compared with the Taxus stent (1.14 ± 0.64 and 0.55 ± 0.61 mm).

In patients with lesions carrying a high risk of restenosis, the Genous stent resulted in a non-significant higher rate of TVF compared with the Taxus stent mainly due to more repeat revascularizations in the Genous stent group. There were four stent thromboses with Taxus stent, none with the Genous stent.

Acute TR grades III–IV was created in 13 sheep (54–75 kg) via papillary muscle and chordae avulsion using a 0.07 inch wire blade. Successful creation of TR was confirmed using angiography and by a prominent ventricular wave in central venous pressure recording. Two self-expanding nitinol stents containing a porcine pulmonary valve were then implanted in the IVC and SVC in a transcatheter approach. Implantation was performed through the right jugular vein by means of a 21 F catheter and guided by fluoroscopy. Haemodynamics were continuously monitored and valve function was verified by angiography and epicardial echocardiography. After successful implantation and proof of concept in the acute study (acute group, n = 9), chronic studies were (n = 4, 4 weeks follow-up) performed. Tricuspid regurgitation grades III–IV was successfully created in all animals and resulted in a significant reduction of CO. A ventricular wave in the IVC of 16.2 ± 2.33 mmHg (acute group) and 14.9 ± 1.71 mmHg (chronic group) confirmed the presence of severe TR. After deployment of the IVC and the SVC valve, the ventricular wave in the IVC significantly decreased to 13.9 ± 2.97 mmHg (acute group) and 12.7 ± 1.15 (chronic group), whereas CO significantly increased to 4.20 ± 0.84 L/min (acute group) and 5.4 ± 0.67 L/min (chronic group). At autopsy, correct device position was verified in all successfully implanted animals, no macroscopic damage resulting from the implantation procedure was observed.

In high-grade tricuspid insufficiency, percutaneous implantation of valved stents in the central venous position reduces venous regurgitation and improves haemodynamics in the animal experiment. Implantation of one or two valves in central venous position is technically feasible. Functional replacement of the insufficient tricuspid valve leads to an increase in CO. This technique expands the potential therapeutic options for patients with relevant tricuspid valve regurgitation having a high risk for open heart surgery.

In DM (n = 22) and in healthy controls (n = 17), coronary artery calcification (CAC) was assessed with electron beam tomography and carotid intima–media thickness (IMT) with ultrasound, whereas coronary function was determined with positron emission tomography-measured myocardial blood flow (MBF) at rest, during cold pressor testing (CPT), and during adenosine stimulation at baseline and after FU. The decrease in plasma glucose in DM after a mean FU of 14 ± 1.9 months correlated with a lower progression of CAC and carotid IMT (r = 0.48, P ≤ 0.036 and r = 0.46, P ≤ 0.055) and with an improvement in endothelium-related MBF to CPT and to adenosine (r = 0.46, P ≤ 0.038 and r = 0.36, P ≤ 0.056). After adjusting for metabolic parameters by multivariate analysis, the increases in MBF to CPT after glucose-lowering treatment remained a statistically significant independent predictor of the progression of CAC (P ≤ 0.001 by one-way analysis of variance).

In DM, glucose-lowering treatment may beneficially affect structure and function of the vascular wall, whereas the observed improvement in endothelium-related coronary artery function may also mediate direct preventive effects on the progression of CAC.

URGENT Dyspnoea was an international, multi-centre, observational cohort study of AHF patients managed conventionally and enrolled within 1 h of first hospital medical evaluation. Patient-assessed dyspnoea was recorded in the sitting position at baseline and at 6 hours by Likert and visual analog scales. Less symptomatic patients were placed supine to determine whether this provoked worsening dyspnoea (orthopnoea). Of the 524 patients with AHF, the mean age was 68 years, 43% were women, and 83% received intravenous diuretics. On a 5-point Likert scale, dyspnoea improvement was reported by 76% of patients after 6 h of standard therapy. Supine positioning (orthopnoea test) led to worse dyspnoea in 47% of patients compared to sitting upright.

When sitting upright, dyspnoea in the sitting position improves rapidly and substantially in patients with AHF after administration of conventional therapy, mainly intra-venous diuretics. However, many patients remain orthopnoeic. Improving the methodology of clinical trials in AHF by standardizing the conditions under which dyspnoea is assessed could enhance their ability to identify effective treatments. Relief of orthopnoea is clinically valuable and may represent a useful goal for clinical trials.

We applied 7 cm H₂O CPAP for 30 min to healthy individuals after acute (Capanna Margherita, CM, 4559 m, 2 days permanence, and <36 h hike) and prolonged altitude exposure (Mount Everest South Base Camp, MEBC, 5350 m, 10 days permanence, and 9 days hike). At CM, CPAP reduced heart rate and systolic pulmonary artery pressure while haemoglobin oxygen saturation increased from 80% (median), 78–81 (first to third quartiles), to 91%, 84–97 (P < 0.001). After 10 days at MEBC, haemoglobin oxygen saturation spontaneously increased from 77% (74–82) to 86% (82–89) (P < 0.001) while heart rate (from 79, 64–92, to 70, 54–81; P < 0.001) and respiratory rate (from 15, 13–17, to 13, 13–15; P < 0.001) decreased. Under such conditions, these parameters were not influenced by CPAP.

After ascent excessive lung fluids accumulate affecting haemoglobin oxygen saturation and, in these circumstances, CPAP is effective. Acclimatization implies spontaneous haemoglobin oxygen saturation increase and, after prolonged altitude exposure, CPAP is not associated with HbO₂-sat increase suggesting a reduction in alveolar fluids.

The dataset comprised 52 693 patients from 123 centres in 14 countries: 42 138 (80%) were nitrate-naïve and 10 555 (20%) were on chronic nitrates at admission. In nitrate-naïve patients, admission diagnosis was ST-segment elevation myocardial infarction (STEMI) in 41%, whereas 59% presented with non-ST-segment elevation acute coronary syndrome (NSTE-ACS). In contrast, only 18% nitrate users showed STEMI, whereas 82% presented with NSTE-ACS. Thus, among nitrate users clinical presentation was tilted toward NSTE-ACS by more than four-fold, STEMI occurring in less than one of five patients (P < 0.0001). After adjustment (age, sex, medical history, prior therapy, revascularization, previous angina), chronic nitrate use remained independent predictor of NSTE-ACS (OR 1.36; 95% CI 1.26–1.46; P < 0.0001). Furthermore, regardless of presentation, within both STEMI and NSTEMI populations, antecedent nitrate use was associated with significantly lower levels of CK-MB and troponin (P < 0.0001 for all).

In this large multinational registry, chronic nitrate use was associated with a shift away from STEMI in favour of NSTE-ACS and with less release of markers of cardiac necrosis. These findings suggest that in nitrate users acute coronary events may develop to a smaller extent. Randomized, placebo-controlled trials are warranted to establish whether nitrate therapy may pharmacologically precondition the heart toward ischaemic episodes.

All consecutive patients with diabetes mellitus in Sweden who underwent percutaneous coronary intervention were entered into the Swedish Coronary Angiography and Angioplasty Registry (SCAAR) during 2003–06 with complete follow-up for 1–4 years (median 2.5). Patients who received at least one DES (n = 4754) were compared with those who received only bare metal stents (BMS) (n = 4956) at the index procedure. Combined outcome of death or myocardial infarction (MI) showed no difference for DES vs. BMS, relative risk (RR), 0.91 [95% confidence interval (CI), 0.77–1.06]. Myocardial infarction was significantly less common with DES in patients who received only one stent RR, 0.80 (95% CI, 0.66–0.96). The restenosis rate was 50% lower in DES-treated patients RR, 0.50 (95% CI, 0.35–0.70) and was associated with a higher adjusted RR of MI, RR, 5.03 (95% CI, 4.25–5.97). DES was associated with reduced restenosis rates in all subgroups of diabetic patients with the greatest benefit in stent diameters <3 mm or stent length >20 mm. The number of lesions treated with DES to prevent one restenosis ranged from 11 to 47 in various subgroups.

This real-life registry study shows that restenosis was halved by DES in diabetic patients with stable or unstable coronary disease, with similar risk of death or MI up to 4 years compared with BMS.

In 50 consecutive patients (body weight ≤ 100 kg, sinus rhythm ≤60 b.p.m. after pre-medication, coronary CTA was performed using a dual-source CT system with 2 x 128 x 0.6 mm collimation, 0.28 s rotation time, a pitch of 3.2 or 3.4, 100 kV tube voltage and current of 320 mA s. Data acquisition was prospectively triggered at 60% of the R–R interval and completed within one cardiac cycle. Image quality was evaluated using a four-point scale (1 = absence of any artefacts to 4 = uninterpretable). In all 50 patients, imaging was successful. Mean duration of data acquisition was 258 ± 20 ms. Mean dose-length product was 62 ± 5 mGy cm, the effective dose was 0.87 ± 0.07 mSv (0.78–0.99 mSv). Of the 742 coronary artery segments, 94% had an image quality score of 1, 5.0% a score of 2, 0.9% a score of 3, and 4 segments (0.5%) were ‘uninterpretable’.

In non-obese patients with a low and stable heart rate, prospectively ECG-triggered high-pitch spiral coronary CTA provides excellent image quality at a consistent dose below 1.0 mSv.

Cavotricuspid isthmus ablation was performed in an interventional RTMRI suite by using a novel 7 French, steerable, non-ferromagnetic ablation catheter in a porcine in vivo model (n = 20). The catheter was introduced and navigated by RTMRI visualization only. Catheter position and movement during manipulation were continuously visualized during the entire intervention. Two porcine prematurely died due to VT/VF. Anatomical completion of the CTI ablation line could be achieved after a mean of 6.3±3 RF pulses (RF energy: 1807±1016.4 Ws/RF pulse, temperature: 55.9±5.9°C) in n = 18 animals. In 15 of 18 procedures (83.3%) a complete CTI block was proven by conventional mapping in the electrophysiological (EP) lab.

Completely non-fluoroscopic ablation guided by RTMRI using a steerable and non-ferromagnetic catheter is a promising novel technology in interventional electrophysiology.

We evaluated 1063 patients (age: 50 ± 12 years, 676 (64%) females) without significant narrowing (<30%) on coronary angiography who underwent invasive assessment of coronary endothelial function. Coronary blood flow (CBF) in response to the endothelium-dependent vasodilator acetylcholine was evaluated as well as the microvascular (endothelium-independent) coronary flow reserve (CFR) in response to intracoronary adenosine. Coronary blood flow and CFR were analysed in relation to the FRS and the presence of traditional and novel risk factors. The estimated 10 years risk in this group was 5.4 ± 5.2%. Higher FRS was associated with lower CBF in men (P = 0.008), and was a univariate predictor of lower CFR (P = 0.012) in all patients. Multivariable analysis identified a higher FRS (P < 0.001), female sex (P < 0.001) and a positive family history of coronary disease (P = 0.043) as independent predictors of reduced CFR.

In patients without obstructive coronary disease, a higher FRS was an independent predictor of reduced CFR. The current study provides insight into the relation between cardiac risk profile and coronary microcirculatory function, and suggests that impaired microcirculatory vasodilator function may be present even in patients with a low to intermediate Framingham score.

ECG-amplitude sums were measured in 44 normals, 34 athletes, a hospital-cohort of 87 HCM-patients, and 29 HCM-patients with sudden death or cardiac arrest (HCM-CA). HCM-patients with sudden death or cardiac arrest had substantially higher ECG-amplitudes than the HCM-cohort for limb-lead and 12-lead QRS-amplitude sums, and amplitude–duration products (P = 0.00003–P = 0.000002). Separation of HCM-CA from the HCM-cohort is obtained by limb-lead QRS-amplitude sum ≥7.7 mV (odds ratio 18.8, sensitivity 87%, negative predictive value (NPV) 94%, P < 0.0001), 12-lead amplitude–duration product ≥2.2 mV s (odds ratio 31.0, sensitivity 92%, NPV 97%, P < 0.0001), and limb-lead amplitude–duration product ≥0.70 mV s (odds ratio 31.5, sensitivity 93%, NPV 96%, P < 0.0001). Sensitivity in HCM-patients <40 years is 90, 100, and 100% for those ECG-variables, respectively. Qualitative analysis showed correlation with cardiac arrest for pathological T-wave-inversion (P = 0.0003), ST-depression (P = 0.0010), and dominant S-wave in V₄ (P = 0.0048). A risk score is proposed; a score ≥6 gives a sensitivity of 85% but a higher positive predictive value than above measures. Optimal separation between HCM-CA <40 years and athletes is obtained by a risk score ≥6 (odds ratio 345, sensitivity 85%, specificity 100%, P < 0.0001).

Twelve-lead ECG is a powerful instrument for risk-stratification in HCM.

We included 5613 persons from the Cardiovascular Health Study (CHS) with an average of 11.5 year follow-up. We determined incidence rates and hazard ratios (HRs) in persons with heart failure compared with persons without heart failure and mortality hazards following these fractures. Annualized incidence rates for hip fractures were 14 per 1000 person-years in heart failure and 6.8 per 1000 person-years without heart failure. Unadjusted and multivariable adjusted HRs for hip fracture associated with heart failure in men were 1.87 (95% CI 1.2–2.93) and 1.59 (95% CI 0.93–2.72), respectively. Respective HRs for women were 1.75 (95% CI 1.27–2.4) and 1.41 (95% CI 0.98–2.03). Mortality hazard was ~2-fold greater in patients with heart failure and hip fracture compared with those having heart failure alone.

Persons with heart failure are at high risk for hip fractures. However, much of the association between hip fractures and heart failure is explained by shared risk factors. Hip fractures are a substantial contributor to mortality in men and women with heart failure.

Fifty-six consecutive patients underwent OCT during angiographic follow-up at 9 months. OCT images were acquired using a non-occlusive technique at a pullback speed of 3 mm/s. Data were analysed using a Bayesian hierarchical random-effects model, which accounted for the correlation of lesion characteristics within patients and implicitly assigned analytical weights to each lesion depending on the number of struts observed per lesion. Primary outcome was the difference in percentage of uncovered struts between BESs and SESs. Twenty patients were included in the analysis in the BES group (29 lesions with 4592 struts) and 26 patients in the SES group (35 lesions with 6476 struts). A total of 83 struts were uncovered in the BES group and 407 out of 6476 struts were uncovered in the SES group [weighted difference –1.4%, 95% confidence interval (CI) –3.7 to 0.0, P = 0.04]. Results were similar after adjustment for pre-procedure lesion length, reference vessel diameter, number of implanted study stents, and presence of stent overlap. There were three lesions in the BES group and 15 lesions in the SES group that had ≥5% of all struts uncovered (difference –33.1%, 95% CI –61.7 to –10.3, P < 0.01).

Strut coverage at an average follow-up of 9 months appears to be more complete in patients allocated to BESs when compared with SESs. The impact of this difference on clinical outcome and, in particular, on the risk of late stent thrombosis is yet to be determined.

The mode of the onset and the coupling intervals of the premature ventricular contractions (PVCs) initiating VF episodes were analysed in patients with BrS (n = 8) or ER who experienced sudden cardiac death/syncope or repeated appropriate implantable cardioverter defibrillator shocks. Among the 11 patients with ER, 5 presented with electrical storm (ES, four or more recurrent VF episodes/day). The five ES patients displayed a dramatic but very transient accentuation of J waves across the precordial and limb leads prior to the development of ES. Ventricular fibrillation episodes were more commonly initiated by PVCs with a short–long–short (SLS) sequence in ER (42/58, 72.4%) vs. BrS patients (13/86, 15.1%, P < 0.01). Coupling intervals were significantly shorter in the ER group compared with those with BrS [328 (320, 340) ms vs. 395 (350, 404) ms, P < 0.01].

Our study provides additional evidence in support of the hypothesis that ER pattern in the ECG is not always benign. Transient augmentation of global J waves may be indicative of a highly arrhythmogenic substrate heralding multiple episodes of VF in patients with ER pattern. Ventricular tachycardia/VF initiation is more commonly associated with an SLS sequence, and PVCs display a shorter coupling interval in patients with ER pattern compared with those with BrS.

Between January 2001 and May 2007, CRT implantation was performed in 303 patients (247 men, 82%). The mean follow-up was 31 ± 19 months. Population characteristics were a mean age of 70 ± 10 years old; 56 female; aetiology includes (202 dilated and 101 ischaemic cardiomyopathy); NYHA class 3.2 ± 0.3; LVEF (26 ± 6%), and a QRS width of 171 ± 31 ms. Thirteen patients developed a DRI: endocarditis in four, pocket erosion in three, pocket abscess in five, and septicaemia in one. The prevalence of DRI was 4.3%. By univariate analysis, predictive factors of DRI were: procedure time (skin to skin: median of 85 vs. 57.5 min; P = 0.03), re-intervention (54 vs. 6.5%; P < 0.0001), haematoma (31 vs. 8.6% P = 0.01), lead dislodgement (23 vs. 6.2%; P = 0.03), dialysis (23.1 vs. 1.72%; P = 0.003), and procedure type [CRT-ICD (8.6%) vs. CRT PM (1.6%) or system up-grade (1.5%); P = 0.03]. Significant correlations were found between re-intervention and lead dislodgement (r = 0.8; P < 0.001), haematoma (r = 0.2; P < 0.001). Four independent predictive factors of DRI were identified as procedure time (P = 0.002); dialysis (P = 0.0001); re-intervention (P = 0.006), and procedure type (CRT-ICD vs. other procedures; P = 0.01).

This study found that the prevalence of CRT DRI is close to 4.3% at 2.6 years (1.7% per year incidence). Four independent predictive factors of infections were identified including re-intervention, procedure time, dialysis, and primo CRT-ICD implantation. These parameters should be part of the risk–benefit evaluation in patients selected for CRT implantation.

Secondary post hoc analyses of 5 µM ADP-induced IPA and bleeding complications assessed by TIMI, GUSTO, and BleedScore^TM scales in a combined data set consisting of patients with documented CAD (n = 246) and previous IS (n = 117). Demographic characteristics differ substantially depending on the underlying vascular disease; however, IPA and bleeding risks were similar between CAD and IS. All three bleeding scales adequately captured serious haemorrhagic events, where the TIMI scale was the most exclusive, whereas BleedScore^TM was the most inclusive. Over half of all patients experienced superficial event(s), most commonly occurring during two to three distinct bleeding episodes. There was no correlation between IPA and duration of antiplatelet therapy. Inhibition of platelet aggregation >50% strongly correlates with minor (r² = 0.58, P < 0.001; c-statistic = 0.92), but not severe (r² = 0.11, P = 0.038; c-statistic = 0.57), bleeding events.

Chronic oral combination antiplatelet regimens are associated with a very high (56.5–60.7%) prevalence of superficial bleeding episodes, which are grossly underestimated in trials and registries. The role of such frequent mild complications for the overall benefit of antiplatelet therapy is entirely unknown, as is their effect on compliance. Although IPA is well suited for defining the risk of minor complications, prediction of more severe bleeding events may be challenging.

Between August 2004 and July 2006, 990 patients in 42 centres were enrolled in a prospective, multicentre, non-randomized global VH registry. Coronary artery imaging was performed by conventional IVUS and RF-IVUS. The four RF-IVUS plaque components [dense calcium (DC), necrotic core (NC), fibrous (F) tissue, and fibro fatty (FF)] were analysed in every recorded frame. The results were expressed as mean cross-sectional areas, absolute volume, and percentage of total plaque volume. Risk factor assessment included evaluation of family history of previous myocardial infarction (MI), past or current smoking, diabetes mellitus, hypertension, and the laboratory measurements. Patients with diabetes had an increased relative proportion of NC (6.47 ± 0.28 vs. 5.86 ± 0.14%, P = 0.037) and DC (4.58 ± 0.27 vs. 3.90 ± 0.14%, P = 0.017), and patients with hypertension had an increased relative proportion of FF, DC (4.35 ± 0.16 vs. 3.57 ± 0.17%, P = 0.02) and NC (6.24 ± 0.17 vs. 5.60 ± 0.19%, P = 0.01). Compared with patients with LDL-C <100 mg/dL, patients with LDL-C >160 mg/dL had higher plaque volume (342.1 ± 26.2 vs. 318.6 ± 10.7 mm³). Linear regression analysis showed a correlation between the level of HDL-C and F (r = –0.149, P < 0.01), FF (r = –0.106, P < 0.01), and NC (r = –0.90, P < 0.05). The level of LDL correlated with F (r = 0.110, P < 0.01). Patients with prior MI have an increased percentage of F (30.03 ± 0.59 vs. 28.20 ± 0.37%, P = 0.009). Smoking had no relevant effect on plaque composition. Treatment with acetylsalicylacid and statins reduced FF with altering plaque volume.

Radiofrequency-IVUS detects marked differences in coronary plaque composition related to the risk factor profile with particular focus on lipid levels. Greater amounts of NC were associated with diabetes, hypertension, MI, and low HDL-C. The effects of treatment of changes related to plaque composition are underway.

We analysed 11 256 patients enrolled in VALIANT. Landmark analysis and Cox proportional hazards modelling were used to predict SCD during hospitalization, from discharge to 30 days, 30 days to 6 months, and 6 months to 3 years. The cumulative incidence of SCD was 8.6% (n = 965). Initially, higher baseline heart rate [HR 1.20 per 10 b.p.m. (95% CI 1.06–1.37)] and impaired baseline creatinine clearance [HR 0.82 per 10 mL/min (95% CI 0.74–0.91)] were stronger predictors of SCD. With long-term follow-up, prior MI [HR 1.71 (95% CI 1.39–2.10)], initial left ventricular ejection fraction <40% [HR 0.67 per 10% (95% CI 0.58–0.78)], and recurrent cardiovascular events [HR 1.47 for rehospitalization (95% CI 1.17–1.86)] were more robust risk stratifiers for SCD. Atrial fibrillation post-MI was associated with an increased risk of SCD over the entire follow-up period. As time passed, the associations between baseline clinical characteristics and SCD decreased and time-updated assessments became more important.

Predictors of SCD change with time after MI. Future studies of risk stratification for SCD should account for changes in these factors with time after MI.

In the population-based Prevention of Renal and Vascular End-stage Disease (PREVEND) study, 8383 subjects were prospectively followed for a median period of 7.5 years. There were 4181 (49.9%) males and 4202 (50.1%) females, mean age was 49.3 ± 12.7 years (range 28–75). Median NT-proBNP at baseline was 37.7 pg/mL (IQR 16.8–73.8). All-cause death occurred in 437 (5.2%) subjects and there were 557 (6.6%) CV events. Higher levels of plasma NT-proBNP were related to higher event rates. When adjusted for age, gender, and other relevant covariates, each doubling of NT-proBNP remained significantly associated with a 22% increased risk for all-cause mortality (P < 0.001) and a 16% increased risk of CV events (P < 0.001).

In this large community-based cohort, plasma NT-proBNP was a strong predictor of death and a wide range of CV events.

PAPP-A serum levels were measured in 170 patients participating in the monitor! trial, a prospective dynamic dialysis cohort multicenter study in Switzerland. Patients were followed up for a median time of 17 months after measuring PAPP-A, and evaluated for death of any cause. Survivors and non-survivors were compared with regard to baseline PAPP-A concentrations. A multivariate logistic regression analysis for death was performed including PAPP-A, age, sex, number of comorbidities, dialysis vintage, Kt/V, IL-6, C-reactive protein, parathyroid hormone (PTH), Ca x PO₄ product, and total serum cholesterol. A cut-off value for PAPP-A was calculated for discrimination between patients with low and high mortality risk, respectively. A total of 23 deaths occurred during follow-up, equalling an incidence rate of 0.1. Baseline median PAPP-A levels were 40% higher in non-survivors vs. survivors (P = 0.023). In a multivariate analysis, only PAPP-A, age, and Ca x PO₄ product were independent predictors of mortality. A cut-off value of 24 mIU/L discriminates significantly (P = 0.015) between patients at low or high risk for death with a negative predictive value of 91%.

PAPP-A is a novel and independent short-time predictor of mortality in a maintenance HD population. The pathogenetic relevance of PAPP-A, particularly in the development of cardiovascular disease, remains to be further elucidated.

A cohort of 106 patients with FD (52 males; 54 females) from three European centres were studied. The diameter of the thoracic aorta was assessed at three levels (sinus of Valsalva, ascending aorta, and descending aorta) using echocardiograms and cardiovascular magnetic resonance imaging. Aortic dilation at the sinus of Valsalva was found in 32.7% of males and 5.6% of females; aneurysms were present in 9.6% of males and 1.9% of females. No aortic dilation was observed in the descending aorta. There was no correlation between aortic diameter at the sinus of Valsalva and cardiovascular risk factors.

Fabry disease should be considered as a cardiovascular disease that affects the heart and arterial vasculature, including the thoracic aorta. Thus, patients with FD should be closely monitored for the presence, and possible progression and complications of aortic dilation.

Clinical Trial Registration: Protocol 101/01. Ethics committee, Faculty of Medicine, Lausanne.

Data were prospectively collected on HF patients hospitalized in all public hospitals in Israel as part of a national survey (HFSIS). Atrial fibrillation patients were subdivided into intermittent and chronic AF subgroups. During March–April 2003, we enrolled 4102 HF patients, of whom 1360 (33.2%) had AF [600 (44.1%) intermittent, 562 (41.3%) chronic]. Patients with AF were older (76.9 ± 10.5 vs. 71.7 ± 12.6 years, P = 0.0001), males, with preserved LV systolic function. Crude mortality rates for AF patients were progressively and consistently higher during hospitalization and during the 4-year follow-up period, especially in the chronic AF group (P = 0.0001). After covariate adjustment, AF was associated with increased 1-year mortality [HR 1.19, 95% CI (1.03–1.36)].

AF was present in a third of hospitalized HF patients, and identified a population with increased mortality risk, largely due to co-morbidities.

We studied 2947 patients who underwent EE. Wall motion score index (WMSI) was evaluated at rest, peak, and post-exercise. Ischaemia was defined as the development of new or worsening wall motion abnormalities with exercise. Separate analyses for all-cause mortality and major cardiac events (MACE) were performed. Ischaemia developed in 544 patients (18.5%). Among them, ischaemia was detected only at peak exercise in 124 patients (23%), whereas 414 (76%) had ischaemia at peak plus post-exercise imaging and six patients (1%) had ischaemia only at post-exercise. During follow-up, 164 patients died. The 5-year mortality rate was 3.5% in patients without ischaemia, 15.3% in patients with peak ischaemia alone, and 14% in patients with post-exercise ischaemia (P < 0.001 normal vs. ischaemic groups). In the multivariate analysis, post-exercise WMSI was an independent predictor of MACE [hazard ratio (HR) 1.87, 95% confidence interval (CI) 1.09–2.19, P = 0.02]. Peak exercise WMSI was an independent predictor of MACE (HR 2.19, 95% CI 1.30–3.69, P = 0.003) and mortality (HR 1.58, 95% CI 1.07–2.35, P = 0.02). The addition of peak EE results to clinical, resting echocardiography, exercise variables, and post-EE provided incremental prognostic information for MACE (P = 0.04) and mortality (P = 0.04).

Peak treadmill EE provides significant incremental information over post-EE for predicting outcome in patients with known or suspected CAD.

Pooled analysis of OASIS 5 and 6 data involving 32 170 patients with ACS with and without ST-segment elevation was performed. The association between baseline haemoglobin and major bleeding or ischaemic events was examined using multiple regression model. Main outcome measures were 30-day rates of major bleeding, death, and death/myocardial infarction (MI) analysed according to baseline haemoglobin levels. Baseline haemoglobin level independently predicted the risk of overall, procedure-related, and non-procedure-related major bleedings at 30 days [odds ratio (OR) 0.94, 95% CI 0.90–0.98; OR 0.94, 95% CI 0.90–0.99; and OR 0.89, 95% CI 0.83–0.95, respectively, per 1 g/dL haemoglobin increment above 10 g/dL]. In addition, a curvilinear relationship between baseline haemoglobin levels and death at 30 days was observed with a 6% decrease in the risk for every 1 g/dL haemoglobin increment above 10 g/dL up to 15.9 g/dL (OR 0.94, 95% CI 0.90–0.98) and a 19% increase above this value (OR 1.19, 95% CI, 0.98–1.43). A similar relationship for the composite outcome of death/MI was observed.

A low baseline haemoglobin level is an independent predictor of the risk of major bleeding in ACS as well as of the risk of death and death and MI. Among other predictors of bleeding risk, baseline haemoglobin should be taken into account in patients presenting with ACS.

Clinical trial registration: ClinicalTrials.gov number, NCT00139815.

http://clinicaltrials.gov/ct2/show/NCT00139815?term=NCT00139815&rank=1.

During the period 1985–2007, PAB operations were performed in 227 children at Rikshospitalet. Of these children, 14.5% (n = 33) were treated by balloon dilatation of the PAB. Nine were treated twice. The intention of the procedure was total debanding in 17 and palliative treatment by stepwise dilatation of the PAB in 16 patients. Median follow up time was 59 months. The mean reduction of the gradient was more pronounced in the first group (37.0 ± 19.0 vs. 14.5 ± 10.3 mmHg, P < 0.001). The average mean oxygen saturation improved, however, significantly within the palliated group. The median time for reintervention after stepwise dilatation was 9 months. Serious, procedure-related complications occurred in 2 of 42 catheterizations (4.8%). Debanding by catheter replaced surgery in 8 of the 17 patients (47%).

We consider catheter debanding a valuable alternative in selected cases. Combination with additional interventional techniques may extend the future indications.

The study population included a consecutive cohort of 1019 patients treated with PCI [n = 741 bare-metal stent (BMS) and n = 278 drug-eluting stent (DES)] due to symptomatic coronary artery disease. Residual platelet activity was assessed by adenosine disphosphate (20 µmol/L)-induced PA after 600 mg clopidogrel loading dose. Maximum RPA was measured as peak of aggregation, final RPA was measured 5 min after addition of agonist. The primary endpoint was the occurrence of ST within 3 months defined according to academic research consortium (ARC) criteria. Final and maximum RPA were independent predictors of ST after 3 months. In secondary analysis, the observed effects were independently associated with early ST (HR 1.05, 95% CI 1.01–1.08 and HR 1.05, 95% CI 1.01–1.09, P < 0.01, respectively). However, incidence of 3-month late stent thrombosis (LAT) was not influenced by post-interventional RPA in multivariable analysis.

Post-interventional RPA is associated with the occurrence of early ST in patients treated with either BMS or DES; however, there is no predictive value of RPA for the incidence of 3-month LAT, suggesting the involvement of other possible mechanisms like discontinuation of antiplatelet therapy.

We collected skeletal muscle (n = 27) and myocardial biopsies (n = 24) from control patients (n = 7), patients with NIDDM (n = 9) and patients with LVD (n = 8), who were characterized by euglycaemic–hyperinsulinaemic clamp and positron emission tomography. Comparative studies were carried out in three mouse models. We demonstrate an unrecognized reduction of IRS1 in skeletal muscle of LVD patients and an unexpected increase in cardiac IRS1-PI3K activity in NIDDM and LVD patients. In NIDDM, there was a concomitant reduction in sarcolemmal GLUT4, whereas in patients with LVD sarcolemmal GLUT4 was increased. We confirm activation of IRS1-PI3K and reduction in sarcolemmal GLUT4 in the insulin resistant ob/ob mouse heart where we also demonstrate perturbation of GLUT4 docking and fusion. A direct relationship between PI3K and GLUT4 was demonstrated in mice expressing activated PI3K in the heart and increased GLUT4 at the sarcolemma was confirmed in a mouse model of LVD.

Our data show that the mechanisms of myocardial insulin resistance are different between NIDDM and LVD.

Twenty-three patients were randomized to either 4 weeks in-hospital exercise training (6 x 15 min bicycle/day, 5 days/week) and a hypocaloric diet, followed by a 5 months ambulatory program (30 min ergometer/day, 5 days/week, plus 1 h group exercise/week), or a control group. At the beginning of the study, at 4 weeks, and after 6 months changes in diameter of coronary arteries in response to acetylcholine and mean peak flow velocity were invasively measured; intramural plaques were assessed by intravascular ultrasound. Six months of intervention led to significant improvement of coronary endothelial function, whereas intramural plaque burden remained unchanged. After 4 weeks, endothelial function remained unchanged, however, lowest values for fasting glucose, HbA1c, high-sensitive C-reactive protein, total and LDL-cholesterol, and highest values for mRNA expression in skeletal muscle of p22, gp91, haem oxygenase 1, peroxisome proliferator activator receptor (PPAR) and were observed. There was a continuous increase for AdipoR1, AdipoR2, Glut4, interleukin-6, endothelial nitric oxide synthase, and PPAR-coactivator-1 mRNA expression in skeletal muscle.

This is the first study to demonstrate improvement in coronary endothelial function by a multifactorial intervention which focused on exercise training in patients with T2DM. This coincided with improved markers of hyperglycaemia, insulin sensitivity, and inflammation both in serum and skeletal muscle biopsies.

We evaluated 139 194 patients with NSTE-ACS in the CRUSADE quality improvement initiative. The presenting HR was summarized as 10 beat increments. Patients with systolic BP < 90 mm Hg (4030 patients) were excluded to avoid the confounding effect of cardiogenic shock. An adjusted odds ratio (OR) was calculated using a reference OR = 1 for HR of 60–69 b.p.m. after controlling for baseline variables. Primary outcome was a composite of in-hospital events all-cause mortality, non-fatal re-infarction, and stroke. Secondary outcomes were each of these considered separately. From the cohort of 135 164 patients, 8819 (6.52%) patients had a primary outcome (death/re-infarction or stroke) of which 5271 (3.90%) patients died, 3578 (2.65%) patients had re-infarction, and 1038 (0.77%) patients had a stroke during hospitalization. The relationship between presenting HR and primary outcome, all-cause mortality, and stroke followed a ‘J-shaped’ curve with an increased event rate at very low and high HR even after controlling for baseline variables. However, there was no relationship between presenting HR and risk of re-infarction.

In contrast to patients with stable CAD, in the acute setting, the relationship between presenting HR and in-hospital cardiovascular outcomes has a ‘J-shaped’ curve (higher event rates at very low and high HRs). These associations should be considered in ACS prognostic models.

Routine electrocardiograms taken throughout the study were assessed by Minnesota-code criteria for the presence of new Q-waves without clinical presentation and analysed with blinding to treatment allocation and clinical outcome. Of all MIs, 36.8% were silent. Being male, older age, longer diabetes duration, prior cardiovascular disease (CVD), neuropathy, higher HbA_1c, albuminuria, high serum creatinine, and insulin use all significantly predicted risk of clinical or silent MI. Fenofibrate reduced MI (clinical or silent) by 19% [hazard ratio (HR) 0.81, 95% confidence interval (CI) 0.69–0.94; P = 0.006], non-fatal clinical MI by 24% (P = 0.01), and silent MI by 16% (P = 0.16). Among those having silent MI, fenofibrate reduced subsequent clinical CVD events by 78% (HR 0.22, 95% CI 0.08–0.65; P = 0.003).

Silent and clinical MI have similar risk factors and increase the risk of future CVD events. Fenofibrate reduces the risk of a first MI and substantially reduces the risk of further clinical CVD events after silent MI, supporting its use in type 2 diabetes.

The International Day for Evaluation of Abdominal obesity (IDEA) study evaluated the prevalence of abdominal obesity, elevated body mass index (BMI), and other cardiometabolic risk factors among primary care patients. Abdominal obesity predicted increased diabetes risk, despite socio-economic, demographic, and risk factor differences. Cardiovascular disease was at least two-fold more frequent in Eastern Europe vs. Northwest Europe (P < 0.0001) and 2.5-fold more vs. Southern Europe (P < 0.0001). Waist circumference (WC) predicted increased (P < 0.0001) age- and BMI-adjusted risks of CVD and diabetes. In women, odds ratios (95% confidence intervals) for CVD per 1 SD increase in WC were: Northwest Europe 1.28 (1.18–1.40); Southern Europe 1.26 (1.16–1.37); and Eastern Europe 1.10 (1.03–1.18). Values for diabetes were 1.72 (1.58–1.88), 1.45 (1.35–1.56), and 1.59 (1.46–1.73), with similar findings in men.

Abdominal obesity impacted similarly on the frequency of diabetes across Europe, despite regional differences in cardiovascular risk factors and CVD rates. Increasing abdominal obesity may offset future declines in CVD, even where CVD rates are lower.

Using a classical biochemical strategy, we isolated and identified sphingosine-1 phosphate (S1P) as a proliferative factor present in the plasma of patients with Fabry disease. Plasma S1P levels were significantly higher in 17 patients with Fabry disease compared with 17 healthy controls (225 ± 40 vs. 164 ± 17 ng/mL; P = 0.005). There was a positive correlation between plasma S1P levels and both common carotid artery intima–media thickness and left-ventricular mass index (r² = 0.47; P = 0.006 and r² = 0.53; P = 0.0007, respectively). In an experimental model, mice treated with S1P developed cardiovascular remodelling similar to that observed in patients with Fabry disease.

Sphingosine-1 phosphate participates in cardiovascular remodelling in Fabry disease. Our findings have implications for the treatment of cardiovascular involvement in Fabry disease.

Left ventricular ejection fraction and clinical status were re-assessed in all surviving patients after 61 ± 11 months. Major adverse cardiac events occurred with similar frequency in both groups. When compared with baseline, LVEF assessed by magnetic resonance imaging at 61 months decreased by 3.3 ± 9.5% in the control group and by 2.5 ± 11.9% in the BMC group (P = 0.30). Patients with an infarct transmurality > median appeared to benefit from BMC transfer throughout the 61-month study period (P = 0.040).

A single intracoronary application of BMCs does not promote a sustained improvement of LVEF in STEMI patients with relatively preserved systolic function. It is conceivable that a subgroup of patients with more transmural infarcts may derive a sustained benefit from BMC therapy. However, this needs to be tested prospectively in a randomized trial.

We searched for randomized trials comparing tirofiban vs. placebo or any active control. Odds ratios (OR) were computed from individual studies and pooled with random-effect methods. Thirty-one studies were identified involving 20 006 patients (12 874 comparing tirofiban vs. heparin plus placebo or bivalirudin alone, and 7132 vs. abciximab). When compared with placebo, tirofiban was associated at 30 days with a significant reduction in mortality [OR = 0.68 (0.54–0.86); P = 0.001] and death or myocardial infarction (MI) [OR = 0.69 (0.58–0.81); P < 0.001]. The treatment benefit persisted at follow-up but came at an increased risk of minor bleedings [OR = 1.42 (1.13, 1.79), P = 0.002] or thrombocytopenia. When compared with abciximab, mortality at 30 days did not differ [OR = 0.90 (0.53, 1.54); P = 0.70], but in the overall group tirofiban trended to increase the composite of death or MI [OR = 1.18 (0.96, 1.45); P = 0.11]. No such trend persisted at medium-term follow-up or when appraising studies testing tirofiban at 25 µg/kg bolus regimen.

Tirofiban administration reduces mortality, the composite of death or MI and increases minor bleedings when compared with placebo. An early ischaemic hazard disfavouring tirofiban was noted when compared with abciximab in studies based on 10 but not 25 µg/kg tirofiban bolus regimen.

This Danish follow-up study included 57 053 men and women between 50 and 64 years. Intake of lean and fatty fish was estimated from a detailed and validated food frequency questionnaire. Potential cases of ACS were identified through nationwide medical databases. A total of 1122 cases of ACS were verified during a mean follow-up period of 7.6 years. Among men, intake of fatty fish was associated with a lower risk of ACS. For men in the highest quintile of fish intake compared with the lowest quintile, the hazard ratio was 0.67 (95% confidence interval: 0.53–0.85). The inverse association was observed for intakes >6 g of fatty fish per day with no obvious additional benefit observed for higher intakes. Intake of lean fish was not associated with ACS. There were few cases of ACS and results were not consistent in women.

In conclusion, a modest intake of fatty fish was associated with a lower risk of ACS in middle-aged men, whereas no consistent associations were observed among women.

Participants were 514 healthy men and women (mean age = 62.9 ± 5.7 years), without history or objective signs of CHD, drawn from the Whitehall II epidemiological cohort. Salivary cortisol was measured in response to mental stressors, consisting of a 5 min Stroop task and a 5 min mirror tracing task. Coronary artery calcification (CAC) was measured using electron beam computed tomography. Approximately 40% of the sample responded to the stress tasks with a notable (≥1 nmol/L) increase in cortisol. Significant CAC (Agatston score ≥ 100) was recorded in 23.9% of the sample. The cortisol response group demonstrated a higher risk of significant CAC (odds ratio = 2.20, 95% CI, 1.39–3.47) after adjustments for age, gender, baseline cortisol, employment grade, and conventional risk factors, although cortisol was unrelated to the presence of detectable CAC. Among participants with detectable CAC, the cortisol response group also demonstrated higher log Agatston scores compared with non-responders (age and sex adjusted scores; 4.51 ± 0.15 vs. 3.94 ± 0.13, P = 0.004).

In healthy, older participants without history or objective signs of CHD, heightened cortisol reactivity is associated with a greater extent of CAC. These data support the notion that heightened hypothalamic pituitary adrenal activity is a risk factor for CHD.

Regional myocardial blood flow (MBF) at rest and at Ex was measured with¹⁵O-H₂O and PET in 10 age-matched healthy volunteers (controls), 10 LBBB patients and 10 PM patients with right ventricular pacing off and on (PM off and PM on). Although at Ex septal MBF tended to be higher in LBBB than in controls (3.04 ± 1.18 vs. 2.27 ± 0.72 mL/min/g; P= ns), the ratio septal/lateral MBF was 19% lower in LBBB than in controls (P < 0.05). Similarly, switching PM on at Ex decreased the ratio septal/lateral MBF by 17% (P < 0.005).

The apparent septal perfusion defect in LBBB is mainly due to a relative lateral hyperperfusion rather than to an absolute septal flow decrease. This pattern seems to be reversibly inducible by right ventricular pacing, suggesting a functional rather than a structural alteration.

Changes in LV radial, circumferential, and longitudinal S-and-SR were evaluated in 73 severe AS patients (65 ± 13 years; aortic valve area 0.8 ± 0.2 cm²) with preserved LVEF (61 ± 11%), before and 17 months after AVR. Strain and strain rate data were compared with data from 40 controls (20 healthy individuals and 20 patients with LV hypertrophy) matched by age, gender, body surface area, and LVEF. Compared with controls, severe AS patients had significantly decreased values of LV S-and-SR in the radial (33.1 ± 14.8%, P = 0.2; 1.7 ± 0.5 s^–1, P = 0.003), circumferential (–15.2 ± 5.0%, P = 0.001; –0.9 ± 0.3 s^–1, P < 0.0001), and longitudinal (–14.6 ± 4.1%, P < 0.0001; –0.8 ± 0.2 s^–1, P < 0.0001) directions. At 17 months after AVR, LV S-and-SR significantly improved in all the three directions, whereas LVEF remained unchanged (60 ± 12%, P = 0.7).

In severe AS patients, impaired LV S-and-SR existed although LVEF was preserved. After AVR, a significant S-and-SR improvement in all the three directions was observed. These subtle changes in LV contractility can be detected by 2D-STI.

In 17 patients with HFNEF (median age 69 years, 13 female) and seven age-matched control patients, systolic and diastolic function was analysed by pressure–volume loops at baseline heart rate and during atrial pacing to 100 and 120 min^–1. At baseline, relaxation was prolonged and end-diastolic left ventricular stiffness was higher in HFNEF, whereas all parameters of systolic function were not different from control patients. This resulted in smaller end-diastolic volumes, higher end-diastolic pressure, and a lower stroke volume and cardiac index in HFNEF vs. control patients. During pacing, frequency-dependent upregulation of contractility indices (+dP/dt_max and Ees) occurred similarly in HFNEF and control patients, but frequency-dependent acceleration of relaxation (dP/dt_min) was blunted in HFNEF. In HFNEF, end-diastolic volume and stroke volume decreased with higher heart rates while both remained unchanged in control patients.

In HFNEF, frequency-dependent upregulation of cardiac output is blunted. This results from progressive volume unloading of the left ventricle due to limited relaxation reserve in combination with increased LV passive stiffness, despite preserved force–frequency relation.

Chronically infarcted Goettingen minipigs (n = 20) were divided in four groups that received either media control or one, two, or three doses of SkM (mean of 329.6 x 10⁶ cells per dose) at intervals of 6 weeks and were followed for a total of 7 months. At the time of sacrifice, cardiac function was significantly better in animals treated with SkM in comparison with the control group. A significantly greater increase in the LVEF was detected in animals that received three doses vs. a single dose of SkM. A correlation between the total number of transplanted cells and the improvement in LVEF and LVEF was found (P < 0.05). Skeletal myoblast transplant was associated with an increase in tissue vasculogenesis and decreased fibrosis (collagen vascular fraction) and these effects were greater in animals receiving three doses of cells.

Repeated injection of SkM in a model of chronic MI is feasible and safe and induces a significant improvement in cardiac function.

The Studies of Oral Enoximone Therapy in Advanced HF (ESSENTIAL) programme consisted of two identical, randomized, double-blind, placebo-controlled trials that differed only by geographic location (North and South America: ESSENTIAL-I; Europe: ESSENTIAL-II). Patients with New York Heart Association class III–IV HF symptoms, left ventricular ejection fraction ≤30%, and one hospitalization or two ambulatory visits for worsening HF in the previous year were eligible for participation in the trials. The trials had three co-primary endpoints: (i) the composite of time to all-cause mortality or cardiovascular hospitalization, analysed in the two ESSENTIAL trials combined; (ii) the 6 month change from baseline in the 6 min walk test distance (6MWTD); and (iii) the Patient Global Assessment (PGA) at 6 months, both analysed in each trial separately. ESSENTIAL-I and -II randomized 1854 subjects at 211 sites in 16 countries. In the combined trials, all-cause mortality and the composite, first co-primary endpoint did not differ between the two treatment groups [hazard ratio (HR) 0.97; 95% confidence interval (CI) 0.80–1.17; and HR 0.98; 95% CI 0.86–1.12, respectively, for enoximone vs. placebo]. The two other co-primary endpoints were analysed separately in the two ESSENTIAL trials, as prospectively designed in the protocol. The 6MWTD increased with enoximone, compared with placebo, in ESSENTIAL-I (P = 0.025, not reaching, however, the pre-specified criterion for statistical significance of P < 0.020), but not in ESSENTIAL-II. No difference in PGA was observed in either trial.

Although low-dose enoximone appears to be safe in patients with advanced HF, major clinical outcomes are not improved.

Cold pressor test (3 min hand immersion in ice-water) was performed in 17 women with previous LVBS and in 7 age- and risk factor-matched women with chest pain and normal coronary arteries. At baseline and peak CPT, global and regional LV function, and myocardial perfusion were quantitatively assessed by real-time three-dimensional echocardiography (RT3DE) and myocardial contrast (SonoVue, Bracco) 2D echocardiography (MCE), respectively (Philips iE33 machine, X3-1 and S5-1 probes). Data were analysed off-line (QLab 6.0 software). Peripheral venous catecholamines were assayed by high performance liquid chromatography with electrochemical detection. Cold pressor test induced similar haemodynamic changes and catecholamine increase in controls and LVBS patients. Left ventricular ejection fraction decreased and transient new mid-ventricular and apical motion abnormalities developed in LVBS patients only (quantitative RT3D analysis), without corresponding perfusion defects (MCE). At peak CPT, coronary blood flow and velocity increased (quantitative MCE analysis) in control subjects only.

Cold pressor test induced LV wall motion abnormalities unmatched to regional coronary flow reduction in LVBS patients only. The reduced coronary reserve in response to CPT suggests microvascular dysfunction in LVBS patients.

Prospective data of the Swedish ‘Malmö Preventive Project’ (n = 33 346, 67.3% men, mean age 45.7 ± 7.4 years, mean follow-up 22.7 ± 6.0 years) were analysed. Orthostatic hypotension was found in 6.2% of study participants and was associated with age, female gender, hypertension, antihypertensive treatment, increased heart rate, diabetes, low BMI, and current smoking. In Cox regression analysis, individuals with OH had significantly increased all-cause mortality (in particular those aged less than 42 years) and coronary event (CE) risk. Mortality and CE risk were distinctly higher in those with systolic blood pressure (BP) fall ≥30 mmHg [hazard ratio (HR): 1.6, 95% CI 1.3–1.9, P < 0.0001 and 1.6, 95% CI 1.2–2.1, P = 0.001] and diastolic BP fall ≥15 mmHg (HR: 1.4, 95% CI 1.1–1.9, P = 0.024 and 1.7, 95% CI 1.1–2.5, P = 0.01). In addition, impaired diastolic BP response had relatively greater impact (per mmHg) on CE incidence than systolic reaction.

Orthostatic hypotension can be detected in ~6% of middle-aged individuals and is often associated with such comorbidities as hypertension or diabetes. Presence of OH increases mortality and CE risk, independently of traditional risk factors. Although both impaired systolic and diastolic responses predict adverse events, the diastolic impairment shows stronger association with coronary disease.

One thousand one hundred and seventy-four consecutive patients who were admitted with TnI-positive acute chest pain between March 2004 and July 2007 underwent coronary angiography. In 1012 patients (86%), significant CAD (stenosis >50%) was detected as underlying reason for the acute chest pain. In 82 out of the remaining 162 patients without significant CAD, further workup was performed including both CMR and EMB. Cardiovascular magnetic resonance imaging alone enabled a diagnosis in 66/82 (80%) and EMB alone in 72/82 (88%) patients (P = 0.31). Myocarditis was the most frequent diagnosis by both CMR and EMB in this cohort and was detected with a higher frequency by EMB (58 vs. 81%; P < 0.001). With the combined approach comprising CMR and EMB, a final diagnosis could be established applying the ‘Believe-The-Positive-Rule’ in 78/82 patients (95%). This combined approach turned out to yield more diagnoses than either CMR (P < 0.001) or EMB (P = 0.03) as single techniques, respectively. Comparison of diagnostic CMR procedures with the corresponding diagnostic EMBs demonstrated a substantial match of diagnoses (kappa = 0.70).

Cardiovascular magnetic resonance imaging and EMB have good diagnostic performances as single techniques in patients with TnI-positive acute chest pain in the absence of CAD. The combined application of CMR and EMB yields a considerable diagnostic synergy by overcoming some limitations of CMR and EMB as individually applied techniques.

Between January 2000 and June 2008, all consecutive patients with new-onset AF, who after flecainide exhibited typical Brugada ECG pattern, underwent electrophysiologic, pharmacologic, and genetic testing. Among 346 patients [median age 53 years; interquartile range (IQR), 15], 11 (3.2%; median age 51 years; IQR, 19) diagnosed as lone AF exhibited typical Brugada ECG pattern. Genetic testing was negative. Ventricular tachycardia/ventricular fibrillation (VT/VF) was induced by electrophysiologic testing (five patients) or during flecainide infusion (one patient). Six patients with type 1 ECG pattern and inducible VT/VF underwent ICD implantation. During a median follow-up of 31.5 months (range: 10–85) after ICD implantation, three patients developed BrS and one of them experienced VF. Patients without ICD (five patients) remained asymptomatic during a median follow-up of 74 months. Persistent type 1 pattern occurred only in the three patients who developed BrS.

This study, for the first time, reveals the prevalence of latent BrS in patients with new-onset lone AF, which may precede VT/VF. Persistence of type 1 and ventricular tachyarrhythmias inducibility represents a marker of electrical instability leading to sudden death.

Atrial fibrillation patients (n = 955) with ≥1 additional risk factor for stroke were randomized to receive AZD0837 (150, 300, or 450 mg once daily or 200 mg twice daily) or VKA (international normalized ratio 2–3, target 2.5) for 3–9 months. Approximately 30% of patients were naïve to VKA treatment. Total bleeding events were similar or lower in all AZD0837 groups (5.3–14.7%, mean exposure 138–145 days) vs. VKA (14.5%, mean exposure 161 days), with fewer clinically relevant bleeding events on AZD0837 150 and 300 mg once daily. Adverse events were similar between treatment groups; with AZD0837, the most common were gastrointestinal disorders (e.g. diarrhoea, flatulence, or nausea). d-Dimer, used as a biomarker of thrombogenesis, decreased in all groups in VKA-naïve subjects with treatment, whereas in VKA pre-treated patients, d-dimer levels started low and remained low in all groups. As expected, only a few strokes or systemic embolic events occurred. In the AZD0837 groups, mean S-creatinine increased by ~10% from baseline and returned to baseline following treatment cessation. The frequency of serum alanine aminotransferase ≥3x upper limit of normal was similar for AZD0837 and VKA.

AZD0837 was generally well tolerated at all doses tested. AZD0837 treatment at an exposure corresponding to the 300 mg od dose in this study provides similar suppression of thrombogenesis at a potentially lower bleeding risk compared with dose-adjusted VKA.

This study is registered with ClinicalTrials.gov, number NCT00684307.

Fifty-seven patients (18 females, 39 males, age 8–52 years) after TCPC (lateral tunnel 28, extra-cardiac conduit 29) who underwent surgery during 1994–2001 were examined in our institution. They performed a symptom-limited cardiopulmonary exercise test. Those patients 14 years of age and older filled in the health-related quality-of-life questionnaire SF-36, and those who were 8–13 years of age, the CF-87. Daily activity parameters were obtained by using a triaxial accelerometer over the next three consecutive days. Exercise capacity was severely reduced after TCPC (25.0 mL/min/kg corresponding to 59.7% of age- and sex-related reference values). Daily activity was within the recommendations of the United Kingdom Expert Consensus Group (≥60 min, ≥3 metabolic equivalent, ≥5 days/week) in 72% of the investigated patients. It was reduced in older patients (Spearman r = – 0.506, P < 0.001) and patients with a lower peak oxygen uptake (Spearman r = 0.432, P = 0.001). In children <14 years, mental health was related to daily activity.

Despite their diminished exercise capacity, patients after TCPC show a fairly normal activity pattern. However, their activity depends not only on age, but also on exercise capacity, which, in contrast to healthy people, decreases already from early adolescence on.

We first examined platelet NO signalling in 23 untreated hypertensive (UH) and 23 normotensive (NT) subjects. Platelets from hypertensives exhibited reduced NO synthase activation by albuterol or collagen, as well as suppressed basal and stimulated NO-attributable cyclic guanosine-3',5'-monophosphate, compared with NT. In a second study, comprising 106 subjects with a wide BP range, circulating MPA showed a strong positive correlation with BP. On multiple regression analysis, using a model incorporating systolic BP (SBP), diastolic BP, age, lipids, gender, and smoking status, the only independent predictor of MPA was SBP. Nitric oxide synthase inhibition with N^G-monomethyl-l-arginine increased MPA in NT but not in hypertensives, whereas the NO donor spermine NONOate (SNO) decreased MPA in NT but not in hypertensives. Platelet P-selectin expression was higher in hypertensives than in NT, and its expression was suppressed by SNO in NT only.

Platelet NO production and responsiveness are suppressed with raised BP, and this may contribute to the increase in platelet P-selectin and hence in circulating MPA in hypertension.

Peripheral blood leucocyte telomere length was assessed by telomere restriction fragment analysis in 2509 volunteers free from established CVD, aged approximately 35–55 years old, from the Asklepios Study cohort. Intima-media thickness (IMT) and plaque presence were determined by ultrasonography in both left and right carotid and femoral arteries. Peripheral blood leucocyte telomere length was not a significant independent determinant of IMT (P > 0.3) or plaque presence (P > 0.05), in either artery or either sex. In women but not in men, PBL-TL was a weak determinant of combined (carotid or femoral) plaque presence, adjusted for other risk factors (women: P = 0.03, men: P > 0.4). However, even in women presenting plaques, PBL-TL was still longer than in men.

Since systemic TL is not a substantial underlying determinant of preclinical atherosclerosis, the association between CVD and TL cannot be explained by the fact that subjects with shorter inherited TL are predisposed to atherosclerosis.

Using an anterior MI swine model, near-infrared (NIR) fluorescence was used for in vivo tracking of labelled MPCs [mesenchymal stromal (MSCs), bone marrow mononuclear (BMMNCs), and peripheral blood mononuclear (PBMNCs)] cells early after IC injection. Signal intensity ratios (SIRs) of injected over non-injected (reference) zones were used to report NIR fluorescence emission. Following IC injection, significant differences in mean SIR were documented when MSCs were compared with BMMNCs [1.28 ± 0.10 vs. 0.77 ± 0.11, P < 0.001; 95% CI (0.219, 0.805), respectively] or PBMNCs [1.28 ± 0.10 vs. 0.80 ± 0.14, P = 0.005; 95% CI (0.148, 0.813), respectively]. Differences were maintained during the 60 min tracking period, with only the MSC-injected groups continuously emitting NIR fluorescence (SIR>1). This is correlated with greater cell retention for MSCs relative to mononuclear cells. However, there was evidence of MSC-related vessel plugging in some swine.

Our in vivo NIR fluorescence findings suggest that MPC distribution and retention immediately after intracoronary delivery vary depending on cell population and could potentially impact the clinical efficacy of cardiac cell therapy.

Over 4.8 ± 0.9 years follow-up of 9193 hypertensive patients with electrocardiographic evidence of LVH who were treated with atenolol- or losartan-based regimens, 178 patients (1.9%) suffered SCD. In multivariable analysis including randomized treatment, changing blood pressure over time, and baseline differences between patients with and without SCD, QRS duration was independently predictive of SCD (HR per 10 ms increase = 1.22, P < 0.001). Baseline QRS duration remained a significant predictor of SCD even after controlling for the presence or absence of left bundle branch block (HR = 1.17, P = 0.001) and for changes in ECG LVH severity over the course of the study (HR = 1.16, P = 0.017).

In the setting of aggressive antihypertensive therapy, prolonged QRS duration identifies hypertensive patients at higher risk for SCD, even after controlling for left bundle branch block, other known risk factors for SCD, and changes in blood pressure and severity of left ventricular hypertrophy.

We used the Scottish Coronary Revascularisation Register to undertake a cohort study of all patients undergoing elective PCI in Scotland between April 1997 and March 2006 inclusive. We excluded patients who had previously undergone revascularization. There were 219 deaths within 5 years of 4880 procedures. Compared with normal weight individuals, those with a BMI ≥27.5 and <30 were at reduced risk of dying (HR 0.59, 95% CI 0.39–0.90, 95%, P = 0.014). There was no attenuation of the association after adjustment for potential confounders, including age, hypertension, diabetes, and left ventricular function (adjusted HR 0.59, 95% CI 0.39–0.90, P = 0.015), and there were no statistically significant interactions. The results were unaltered by restricting the analysis to events beyond 30 days of follow-up.

Among patients undergoing percutaneous intervention for coronary artery disease, increased BMI was associated with improved 5 year survival. Among those with established coronary disease, the adverse effects of excess adipose tissue may be offset by beneficial vasoactive properties.

TaqMan 5' nuclease assay was used to genotype the study population of the Helsinki Sudden Death Study, comprising medicolegal autopsies of 700 men. According to adjusted logistic regression analysis, there was a significant interaction between IL-18 genotype and hypertension impacting on the risk of SCD due to coronary heart disease (CHD) (P = 0.011) and the severity of autopsy-verified CAD (P = 0.026). Among GG homozygotes, hypertension was a major risk factor for SCD due to CHD [adjusted odds ratio (OR) 3.75 with 95% CI 1.78–7.91, P < 0.001] and hypertension also associated with larger coronary atherosclerotic plaque areas (P = 0.002) and the occurrence of complicated plaques (adjusted OR 8.38 with 95% CI 2.39–29.33, P < 0.001). Among C allele carriers, hypertension was not a significant risk factor for CHD-related SCD or CAD and did not associate with the development of coronary atherosclerotic plaques. According to gene expression analysis of atherosclerotic tissue samples obtained from live patients, hypertension also interacted significantly with IL-18 genotype affecting the expression of IL-18 (P = 0.030) mRNA and interferon- mRNA (P = 0.004).

Hypertension interacts with IL-18 gene promoter –137 G/C polymorphism, affecting the risk of SCD and the development of coronary atherosclerosis.

We calculated the Calgary Score for 380 patients presenting with T-LOC to a number of departments of our university hospital. Diagnoses of vasovagal syncope based on the Calgary Score were then compared with the final diagnosis, obtained after additional testing and 2 years of follow-up. The sensitivity of the Calgary Score was 87% (95% CI: 82–91%), at a specificity of 32% (95% CI: 24–40%). Most items of the Calgary Score were less discriminative in our study group than in the original population. Incorrectly labelling patients with syncope as vasovagal was most common in patients with psychogenic pseudosyncope (specificity 21%) but also occurred in patients with cardiac syncope (specificity 32%).

The sensitivity of the Calgary Score was comparable with the one in the original study, but its specificity was much lower, limiting its value in patients presenting with T-LOC in a general hospital setting.

Prospective cohort study of 162 consecutive patients undergoing elective carotid endarterectomy. Lipoprotein-associated phospholipase A2 content was quantified by immunoblotting and lysophosphatidylcholine (lysoPC) by liquid chromatography tandem mass spectrometry. Additional biomolecular profiling by immunoblotting included C-reactive protein, p67phox, and matrix metalloproteinase-2 and -9. Macrophage plaque content was determined by quantitative immunostaining, plaque collagen content by quantitative Sirius red staining. Follow-up for cardiac death and non-fatal acute myocardial infarction was accomplished over a period of 48 ± 14 months. Expression of Lp-PLA₂ and lysoPC was higher in carotid plaques of patients with than without cardiac events [median 1.6 (25th, 75th percentile 0.9, 2.5) vs. 0.8 (0.5, 2.0), P = 0.01 and 413 (281, 443) vs. 226 (96, 351) mmol/L, P = 0.03]. Smoking and point increase in carotid Lp-PLA₂ expression but no other traditional cardiovascular risk factor, histological or molecular marker remained predictive of cardiac events in the multivariate Cox proportional hazard analyses [HR 3.65 (1.36–9.83), P = 0.01 and HR 1.34 (1.01–1.77), P = 0.039]. Carotid plaque Lp-PLA₂ expression above the median constituted a more than three times higher risk for cardiac events [HR 3.39 (1.13–10.17), P = 0.03].

Lipoprotein-associated phospholipase A2 expression in carotid artery plaques is a predictor of long-term cardiac outcome. The current study supports the concept of atherosclerosis as a systemic disease with multi-focal complications and personalized medicine.

We assessed carotid intima media thickness (IMT), body mass index (BMI), and other cardiovascular risk factors in 622 healthy volunteers. Using flow-cytometry, we differentiated monocytes into CD14⁺⁺CD16^– and CD16⁺ cells, which we further subdivided into CD14⁺⁺CD16⁺ and CD14⁽⁺⁾CD16⁺ cells. Body mass index was significantly correlated with carotid IMT. High CD16⁺ monocyte counts were significantly associated with both higher BMI and increased carotid IMT. Adjustment for CD16⁺ monocyte counts weakened the correlation between BMI and carotid IMT, suggesting that the increase in CD16⁺ monocyte numbers in obesity may partly explain the association between obesity and IMT.

Our results reveal a significant univariate association between CD16⁺ monocytes and both obesity and subclinical atherosclerosis in low-risk individuals. They are in line with recent observations that CD16⁺ monocytes show high endothelial affinity and a potent capacity to invade vascular lesions and to transform into pro-inflammatory cytokine producing macrophages.

After successful primary percutaneous coronary intervention in 40 patients with anterior AMI, IMR was measured using a pressure-temperature sensor-tipped coronary guidewire. Myocardial viability was quantified by 18F-fluorodeoxyglucose (FDG) positron emission tomography in 38 patients. Echocardiographic regional wall motion was analysed to calculate the anterior wall motion score (A-WMS) and percent change in A-WMS after revascularization and at 6-month follow-up. IMR correlated significantly with regional myocardial FDG uptake (r = –0.738, P < 0.001) and it demonstrated significant correlation with percent change in A-WMS (r = –0.464, P = 0.003). The area under the receiver operating curve of IMR for predicting LV function recovery was 0.89 [95% CI 0.888–0.894].

Index of microcirculatory resistance, a new index representing microvascular integrity, is a reliable early on-site determinant of myocardial viability and LV recovery after primary stenting for AMI.

In 78 patients (mean age 65 ± 9 years) referred for coronary angiography (CA), additional CTA and MPI (using single-photon emission-computed tomography) were performed and the findings not communicated. Detection of flow-limiting stenoses (justifying revascularization) by the combination of CTA and MPI (CTA/MPI) was compared with the combination of quantitative coronary angiography (QCA) plus MPI (QCA/MPI), which served as standard of reference. The findings of both combinations were related to the treatment strategy (revascularization vs. medical treatment) chosen in the catheterization laboratory based on the CA findings. Sensitivity, specificity, positive and negative predictive value, and accuracy of CTA/MPI for the detection of flow-limiting coronary stenoses were 100% each. More than half of revascularization procedures (21/40, 53%) was performed in patients without flow-limiting stenoses and 76% (47/62) of revascularized vessels were not associated with ischaemia on MPI.

The combined non-invasive approach CTA/MPI has an excellent accuracy to detect flow-limiting coronary stenoses compared with QCA/MPI and its use as a gatekeeper appears to make a substantial part of revascularization procedures redundant.

From a total of 652 hearts from transplant donors collected between 1996 and 2007, we selected those from apparently healthy individuals older than 40 years old who died of head trauma or stroke and had no evidence of prior vascular diseases. The coronary arteries were examined by serial sectioning at 3 mm intervals, and all areas of cross-sectional luminal narrowing were processed for histological, immunohistochemical, and morphometric studies. The atherosclerotic plaques were classified according to the American Heart Association Report. A total of 160 hearts were examined. Mean age was 50.3 ± 5.8 years. Sixty-eight hearts had no advanced coronary atherosclerotic lesions (Type I, II, and III of the American Heart classification). In the remaining 92 hearts, we found 179 plaques considered high-risk lesions (American Heart Association Type IV, V, and VI). These plaques were more frequently found in males (P < 0.001) and in those with a higher heart weight (P < 0.001). The median (25th and 75th percentiles) vascular narrowing value using a planimetric analysis was 32% (21–53). No significant association with the cause of death was found (P = 0.09).

High-risk coronary artery plaques not associated with significant vascular lumen reduction exist in 57% of patients who suffered a brain death with a mean of 1.11 lesions prone to rupture per individual.

Characteristics, treatments and 30-day mortality were recorded for 1408/1901 consecutive ACS patients. Changes in global model fit, discrimination, calibration, and reclassification were evaluated upon addition of C-reactive protein to the GRACE risk score. High-C-reactive protein patients (C-reactive protein >22 mg/L, 4th quartile of C-reactive protein) were older, had more comorbidities and worse haemodynamic conditions, received less recommended treatment, and had a four-fold higher 30 day mortality. Multivariable analysis demonstrated high-C-reactive protein as an important and independent predictor of mortality. Addition of high-C-reactive protein in the GRACE model modestly improved global fit, discriminatory capacity (c-statistic from 0.795 to 0.823), and calibration. Patients were divided into four groups according to GRACE risk score prediction: <1, 1 to <5, 5 to <10, and ≥10%. The model with high-C-reactive protein allowed adequate reclassification in 12.2%.

Elevated C-reactive protein level is a modest but independent predictive factor of 30-day mortality in ACS patients, even after adjustment for co-morbidities, haemodynamic conditions, and treatment. Combined with the GRACE risk score, C-reactive protein information improves risk classification.

In a mouse carotid artery photochemical injury model, rapamycin (182 ± 27.5 µg/L) decreased time to thrombotic occlusion by 40%, increased TF activity, and abrogated p70S6K phosphorylation when compared with controls. In vitro, rapamycin, everolimus, and zotarolimus (each 10^–7 mol/l) enhanced TNF--induced TF expression by 2.2-, 1.7-, and 2.4-fold, respectively, which was paralleled by an increase in TF surface activity. Similar to rapamycin, everolimus and zotarolimus abrogated TNF--induced p70S6K phosphorylation under these conditions.

Rapamycin increases TF activity and promotes arterial thrombosis in vivo at concentrations relevant in patients undergoing DES implantation; this effect may increase the thrombogenicity of DES. Since everolimus and zotarolimus augment endothelial TF expression and activity in vitro in a similar manner as rapamycin, these findings may also be relevant for second generation DES.

Patients undergoing CABG received either an intra-aortic filter (Embol-X) (n = 43), designed to reduce solid micro-emboli, a dynamic bubble trap (DBT) (n = 50), designed to reduce gaseous micro-emboli, or no additional device (control group) (n = 50). Cognitive functioning was assessed before and 3 months after CABG. Micro-emboli signals (MES) were detected during surgery using transcranial Doppler (TCD) sonography. Cerebral magnetic resonance imaging (MRI) was carried out before and after surgery. Primary endpoint was the cognitive outcome of the filter groups compared with the controls. Analysis of covariance was performed using the post-operative cognitive test scores as continuous variables in covariance of the corresponding pre-operative scores. Secondary endpoints were the MES rates and the number of acute ischaemic lesions after CABG. Compared with the controls, cognitive functioning of the DBT group was better in executive functioning (t = 2.525, P = 0.0065) and verbal short-term memory (t = 2.420, P = 0.009). The Embol-X group did not perform better in any test. The total number of MES was lower in the DBT group (median 99, P = 0.0019), but not in the Embol-X group (median 162.5, P > 0.05), both compared with controls (median 164.5). After surgery, 17 patients displayed small ischaemic brain lesions on MRI with equal distribution between the groups.

Gaseous micro-embolization contributes to neuropsychological decline, which is measurable 3 months post-operatively. No filter device could protect the brain during CABG completely. However, the use of the DBT tends to improve the cognitive outcome after CABG. Gas filters are recommendable for neuroprotection during cardiac surgery.

A total of 631 CHF patients were followed for cardiovascular death over 3.8 ± 1.4 years; among them 79 (13%) died. All prognostic CPET parameters were related to outcome at univariate analysis, with haemodynamic-derived parameters [peak systolic blood pressure (SBP), peak circulatory power (CP) = peak oxygen consumption (pVO₂) x peak SBP] and exertional oscillatory ventilation (EOV) reaching the highest ² (46.5, 40.9, and 22.6, respectively, all with P < 0.0001). Exertional oscillatory ventilation, although associated with high mortality rate (43 vs. 11%, P < 0.001), was detected in 42 (7%) patients. In non-EOV, again both peak SBP and peak CP reached the highest ² (30.6, and 21.6, respectively, all with P < 0.0001). Regarding CPET parameters, at multivariable analysis, peak SBP was the strongest risk index both in total and non-EOV populations, with 11% risk reduction every 5 mmHg increase.

All traditional CPET risk parameters were informative in beta-blockers CHF patients, but peak SBP, peak CP, and EOV were the most predictive. In this low-risk population, EOV, although underrepresented, considerably enhanced risk stratification, although other ventilatory efficiency indexes provided less impressive predictive content. In large majority of non-EOV patients, peak SBP improved risk evaluation beyond other CPET parameters.

In this study, 1319 men and women aged 25–64 in the fourth Glasgow MONICA study were followed-up for cardiovascular endpoints. Baseline C-reactive protein, fibrinogen, IL-6, IL-18, and TNF were related to risk of CVD. The discriminative value of adding each to the ASSIGN score was assessed using area under the receiver operating characteristic (AUC) and relative integrated percentage improvement in classification (RIDI). During a median of 10.5 years, 151 CVD events occurred. After adjusting for ASSIGN variables, each inflammatory marker except IL-18 had a significant (P < 0.05) association with CVD risk. The AUC using ASSIGN [0.799 (95% CI 0.790–0.809)] was improved by the inclusion of C-reactive protein and TNF [0.805 (95% CI 0.795–0.815); P < 0.03], but not by other combinations. C-reactive protein and TNF yielded a significant RIDI (IL-6 almost so). C-reactive protein and TNF together improved the classification of risk by 11% (95% CI, 3–19%) when added to the ASSIGN variables.

Some inflammatory biomarkers add moderate discriminative information to the ASSIGN CVD risk score. The clinical utility of this information, cost-effectiveness, and optimization should be assessed in future studies.

We studied 273 patients admitted with IE to two centres (derivation cohort n = 192, validation cohort n = 81). The derivation cohort was used to identify independent predictors of 6 months mortality at days 1, 8, and 15 (multivariable Cox regression, P < 0.05). There were six predictors at day 1, five at day 8, and only three at day 15. Whereas heart failure, thrombocytopenia, and severe comorbidity predicted mortality at all three time-points, other predictors were time-dependent (age, tachycardia, renal impairment at day 1; severe embolic events, renal impairment at day 8). These predictors were incorporated into a time-dependent model. The model was validated in an independent cohort with concordance indices of 0.79 (95% CI 0.68–0.91) at day 1, 0.79 (95% CI 0.65–0.93) at day 8, and 0.84 (95% CI 0.73–0.95) at day 15. Six months mortality was 2.4% in patients deemed as low-risk at all time-points, compared with 78.2% in patients classified as high-risk at any evaluation.

Prognostic factors in IE are time-dependent. Time-dependent risk stratification accurately predicts outcome in IE.

In 291 consecutive adults with definite IE who underwent surgery during the active phase, we compared those operated on within the first week of antimicrobial therapy (n = 95) to those operated on later (n = 191). The impact of the timing of surgery on 6-month mortality, relapses, and postoperative valvular dysfunctions (PVD) was analysed using propensity score (PS) analyses. After stratification of the cohort into quintiles based on the PS, ≤1st week surgery was associated with a trend of decrease in 6-month mortality in the quintile of patients with the most likelihood of undergoing this early surgical management [quintile 5: 11% vs. 33%, odds ratio (OR) = 0.18, 95% CI (confidence interval) 0.04–0.83, P = 0.03]. Patients of this subgroup were younger, were more likely to have Staphylococcus aureus infections, congestive heart failure, and larger vegetations. Besides, ≤1st week surgery was associated with an increased number of relapses or PVD (16% vs. 4%, adjusted OR = 2.9, 95% CI 0.99–8.40, P = 0.05).

Surgery performed very early may improve survival in patients with the most severe complicated IE. However, a greater risk of relapses and PVD should be expected when surgery is performed very early.

A total of 190 consecutive ACS patients were imaged using VH-IVUS and analysed retrospectively. Angiographic no-reflow was defined as TIMI flow grade 0, 1, and 2 after stenting. Virtual histology-intravascular ultrasound classified the colour-coded tissue into four major components: fibrotic, fibro-fatty, dense calcium, and necrotic core (NC). Thin-cap fibroatheroma (TCFA) was defined as focal, NC-rich (≥10% of the cross-sectional area) plaques being in contact with the lumen in a plaque burden ≥40%. Of the 190 patients studied at pre-stenting, no-reflow was observed in 24 patients (12.6%) at post-stenting. The absolute and %NC areas at the minimum lumen sites (1.6 ± 1.2 vs. 0.9 ± 0.8 mm², P < 0.001, and 24.5 ± 14.3 vs. 16.1 ± 10.6%, P = 0.001, respectively) and the absolute and %NC volumes (30 ± 24 vs. 16 ± 17 mm³, P = 0.001, and 22 ± 11 vs. 14 ± 8%, P < 0.001, respectively) were significantly greater, and the presence of at least one TCFA and multiple TCFAs within culprit lesions (71 vs. 36%, P = 0.001, and 38 vs. 15%, P = 0.005, respectively) was significantly more common in the no-reflow group compared with the normal-reflow group. In the multivariable analysis, %NC volume was the only independent predictor of no-reflow (odds ratio = 1.126; 95% CI 1.045–1.214, P = 0.002).

In ACS patients, post-stenting no-reflow is associated with plaque components defined by VH-IVUS analysis with larger NC and more TCFAs.

In a prospective case–control study nested in the European Prospective Investigation into Cancer and Nutrition-Norfolk cohort, we examined the associations between circulating levels or activity of C-reactive protein, myeloperoxidase (MPO), secretory phospholipase A2 (sPLA2), lipoprotein-associated phospholipase A2 (Lp-PLA2), fibrinogen, adiponectin, waist circumference, physical activity, and CHD risk over a 10-year period among healthy men and women (45–79 years of age). A total of 1002 cases who developed fatal or non-fatal CHD were matched to 1859 controls on the basis of age, sex, and enrolment period. Circulating levels of C-reactive protein, sPLA2 (women only), fibrinogen, and adiponectin were linearly associated with increasing waist circumference and decreasing physical activity levels. After adjusting for waist circumference, physical activity, smoking, diabetes, systolic blood pressure, low-density lipoprotein and high-density lipoprotein cholesterol levels, and further adjusted for hormone replacement therapy in women, C-reactive protein, MPO (men only), sPLA2, fibrinogen, but not Lp-PLA2 and adiponectin were associated with an increased CHD risk.

Inactive participants with an elevated waist circumference were characterized by deteriorated levels of inflammatory markers. However, several inflammatory markers were associated with an increased CHD risk, independent of underlying CHD risk factors such as waist circumference and physical activity levels.

Four hundred and forty-nine patients with a definite left-sided IE were selected from a prospective, population-based study. Association between VS and 5-year mortality was examined with a Cox model. To determine the impact of different methodological approaches, we also analysed the relationship between VS and mortality in our database, according to each method used in the five previous studies. Valve surgery was performed in 240 patients (53%). It was associated with an increase in short-term mortality [within the first 14 post-operative days; adjusted hazard ratio (HR), 3.69; 95% confidence interval (CI), 2.17–6.25; P < 0.0001] and a decrease in long-term mortality (adjusted HR, 0.55; 95% CI, 0.35–0.87; P = 0.01). At least 188 days of follow-up were required for VS to provide an overall survival advantage. When applying each study's method to our database, we obtained results similar to those reported.

Previous conflicting results appear to be related to differences in statistical methods. When using appropriate models, we found that VS was significantly associated with reduced long-term mortality.

We randomly assigned 184 women, either to a routine or to a selective invasive strategy as a substudy to the OASIS 5 trial, who were followed for 2 years. Meta-analysis of data from previous randomized trials was also done. There were no significant differences between the two treatment strategies in the primary outcome death/myocardial infarction (MI)/stroke [21.0 vs. 15.4%, HR = 1.46, 95% CI (0.73–2.94)], in the secondary outcome death/MI [18.8 vs. 14.3%, HR = 1.39, 95% CI (0.67–2.88)], or separately analysed outcomes MI [12.9 vs. 13.3%, HR = 0.95, 95% CI (0.42–2.19)] or stroke [2.3 vs. 4.4%, HR = 0.67, 95% CI (0.12–3.70)]. However, there were significantly more deaths after 1 year (8.8 vs. 1.1%, HR = 9.01, 95% CI (1.11–72.90) and a higher rate of major bleeding at 30 days [8.8 vs. 1.1%, HR = 11.45, 95% CI (1.43–91.96)] in the routine invasive strategy group. A meta-analysis including 2692 women in previous randomized trials, with a gender perspective, showed no significant difference in the composite outcome death/MI, OR = 1.18, 95% CI (0.92–1.53) but a higher mortality with a routine invasive strategy for women, OR = 1.51, 95% CI (1.00–2.29).

The rate of death, MI, or stroke in women was not different in patients treated with a routine invasive strategy compared with a selective invasive strategy, but there was a concerning trend towards higher mortality. When combined with data from previous trials, there does not appear to be a benefit of an early invasive strategy in women with ACS, which differs from the results in men. These data emphasize the lack of clear evidence in favour of an invasive strategy in women and suggest caution in extrapolating the results from men to women.

All patients with PxAF (n = 855) and PermAF (n = 1126) treated for atrial fibrillation (AF) during 2002 at one of Scandinavia's largest hospitals were followed-up for 3.6 years regarding incidence of stroke. Information about type of AF, comorbidity, medication, and clinical events during follow-up was acquired from medical records and the National Register of Hospital Discharges. The incidence of ischaemic stroke was similar in PxAF and PermAF (26 vs. 29 events/1000 patient years). The multivariable-adjusted hazard ratio (HR) for ischaemic stroke in PxAF compared with PermAF was 1.07 (95% CI 0.71–1.61) in subjects without prior stroke. The corresponding HR for any stroke, ischaemic or haemorrhagic, was 0.89 (95% CI 0.61–1.30). Compared with the general population, ischaemic stroke was twice as common as expected in PxAF after standardization for age and sex (standardized incidence ratio 2.12, 95% CI 1.52–2.71). PxAF patients who took warfarin had approximately half as many ischaemic strokes as those who did not take warfarin (HR 0.44, 95% CI 0.30–0.65).

Ischaemic stroke is about as common in PxAF as in PermAF, and about twice as common as in the general population. Yet, PxAF patients do not receive protective anticoagulant treatment as often as patients with PermAF do. It is therefore important to increase the use of anticoagulants among PxAF patients in accordance with current guideline recommendations.

We searched PubMed and relevant sources from January 2002 to December 2007. Inclusion criteria were: (a) intra-vascular ultrasonography (IVUS) at both post-stent implantation and follow-up; (b) 6–9-month-follow-up IVUS; (c) implantation of either BMS or the following DES: sirolimus, paclitaxel, everolimus, or zotarolimus; and (d) follow-up for LSM. Of 33 articles retrieved for detailed evaluation, 17 met the inclusion criteria. The risk of LASM in patients with DES was four times higher compared with BMS (OR = 4.36, CI 95% 1.74–10.94) in randomized clinical trials. The risk of (very) late ST in patients with LSM (five studies) was higher compared with those without LSM (OR = 6.51, CI 95% 1.34–34.91).

In our meta-analysis, the risk of LASM is strongly increased after DES implantation compared with BMS. Furthermore, LSM seems to be associated with late and very late ST.

Two hundred end-stage heart failure patients [NYHA 3–4 and left ventricular ejection fraction (LVEF)<35%] with QRS>120 ms were included. Echocardiography analysis focused on the following parameters: atrioventricular dyssynchrony, interventricular dyssynchrony, and intraventricular dyssynchrony that integrated radial (PSAX M-mode) and longitudinal [tissue Doppler imaging (TDI)] evaluations for spatial (wall to wall) and temporal (wall end-systole to mitral valve opening) dyssynchrony diagnosis. Following CRT implantation, patients were monitored for 6 months with functional and echo evaluations defining responders by a 15% reduction in end-systolic volume. Mean QRS duration and LVEF were 152 ± 17 ms and 25 ± 8%. There was a CRT response in 57% of patients, independent of QRS width. Mean prevalence of positive criteria was 34 ± 8%. Feasibility and variability averages were 81 ± 20% and 9 ± 4%. In a single parametric approach, ranges of sensitivities and specificities were 18–65% and 45–84% with a mean of 41% and 66%. A multiparametric approach by focusing on criteria combination decreased the mean rate of false-positive results to 14 ± 12%, 5 ± 4%, 2 ± 2%, and 1 ± 2% from one to four parameters, respectively. More than three parameters were associated with a specificity above 90% and a positive predictive value above 65%. Reproducibility of this global strategy was 91%.

A multiparametric echocardiographic strategy based on the association of conventional criteria is a better indicator of CRT response than the existing single parametric approaches.