In 432 patients (59% male, age 58 ± 11 years) referred for cardiac evaluation owing to suspected coronary artery disease (CAD), CS and 64-slice MSCTA were performed. The following events were combined in a composite endpoint: all-cause mortality, non-fatal infarction, and unstable angina requiring revascularization. CS was 0 in 147 (34%) patients, CS 1–99 was present in 122 (28%), CS 100–399 in 75 (17%), CS 400–999 in 56 (13%), and CS ≥ 1000 in 32 (7%). MSCTA was normal in 133 (31%) patients, MSCTA 30–50% stenosis was observed in 190 (44%), and MSCTA ≥50% stenosis in 109 (25%). During follow-up [median 670 days (25th–75th percentile: 418–895)], an event occurred in 21 patients (4.9%). After multivariate correction for CS, MSCTA ≥ 50% stenosis, the number of diseased segments, obstructive segments, and non-calcified plaques were independent predictors with an incremental prognostic value to CS.

MSCTA provides additional information to CS regarding stenosis severity and plaque composition. This additional information was shown to translate into incremental prognostic value over CS.

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.

Prospective, controlled, parallel, multicentre, non-randomized study enrolling 324 primary prevention non-ischaemic HF patients implanted with CRT-D devices from 2004 to 2007: Protect group, 164 patients implanted with a Medtronic Insync III Protect device and Control group, 160 patients utilizing other Medtronic CRT-D devices.

Efficacy was assessed by computing appropriate and inappropriate detections and therapies during follow-up; safety compared hospitalizations and syncopal events between groups. Ninety per cent of both ventricular and supraventricular tachyarrhythmias terminated within the 13–29 beat detection interval with the Protect algorithm. The Protect group showed a significantly better event-free survival to first delivered therapy for total (P = 0.0001), appropriately treated (P = 0.002), and inappropriately treated episodes (P = 0.017). The total number of delivered shocks was significantly lower in the Protect group (22 vs. 59, P < 0.0001). In the Protect group, a significantly reduced HF hospitalization (hazard ratio 0.38, 95% CI 0.15–0.98, P = 0.044) was observed without any increase of syncope or death.

A simplified CRT-D device with fixed long detection reduced overall ICD therapy burden and HF hospitalizations without entailing any additional adverse events in primary prevention non-ischaemic HF patients.

Extracellular matrix (ECM) was examined in human valves obtained from normal, ICM, and DCM hearts. To confirm if ECM changes were directly related to the cardiomyopathy, we developed a porcine model of chronic ICM. Histology and immunohistostaining, as well as non-invasive multiphoton and second harmonic generation (SHG) imaging revealed marked disruption of ECM structures in human valves from ICM and DCM hearts. The ECM was unaffected in valves from normal and acute ICM pigs, whereas chronic ICM specimens showed ECM alterations similar to those seen in ICM and DCM patients. Proteins and proteinases implicated in ECM remodelling, including Tenascin C, TGFβ1, Cathepsin B, MMP2, were upregulated in human ICM and DCM, and porcine chronic ICM specimens.

Valves from cardiomyopathic hearts showed significant ECM deterioration with a disrupted collagen and elastic fibre network. It will be important to determine the impact of this ECM damage on valve durability and calcification in vivo if allografts are to be used from these donors.

Post hoc analysis was performed based on the endpoint of patient-assessed dyspnoea. Changes from baseline at inpatient Day 1 were compared between treatment groups by the van Elteren test. Pre-determined subgroup analyses were also performed. Tolvaptan's effects are greatest within 12 h after first dose with an additional, but modest dyspnoea improvement benefit irrespective of time after admission. Overall, patients continue to report dyspnoea improvement up to 60 h after admission. The window of enrolment, up to 48 h after admission, combined with measurement on ‘Day 1’ led to a wide range over when dyspnoea was assessed.

Post hoc analysis suggests that tolvaptan modestly improves dyspnoea compared with standard therapy alone, regardless if given early or relatively late after hospitalization, and also across major pre-specified subgroups, despite ongoing background therapy aimed at relieving signs and symptoms. Significant variability around when dyspnoea was assessed, in addition to the persistence of dyspnoea despite ongoing background therapy, may influence how future clinical trials assess dyspnoea in acute heart failure syndromes.

Forty-four elective coronary artery bypass grafting patients were randomized to control group or BMCs group (whereby autologous BMCs were administered with each dose of cardioplegia antegradely into the coronaries). Troponin I and CK-MB were measured during the first 48 h after surgery and were not significantly different between the control and BMCs groups. The role of cardiopulmonary bypass (CPB) on the cardioprotective effects of BMCs was also studied using an in vitro model of stimulated ischaemia and reoxygenation on right atrial appendages obtained from controls either before or 10 min after the initiation of CPB. Bone marrow cells significantly reduced myocardial injury in muscles obtained prior to CPB. This effect was comparable with ischaemic preconditioning (IP), although their combination did not afford additional benefit. However, when muscles were harvested after CPB, myocardial injury in the ischaemic group alone was less, and BMCs or IP did not exert further protection.

Bone marrow cells did not afford additional benefit when used as an additive to cardioplegia during CPB. However, BMCs offer cardioprotection as potent as IP, when the heart is not subjected to stress, such as CPB, that per se can precondition the myocardium.

To relate the levels of GDF-15 to indices of CV dysfunction and disease in elderly individuals, serum levels of GDF-15 were measured in 1004 subjects aged 70 years from the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study. Carotid intima-media thickness and plaque burden, and left ventricular (LV) geometry and function were assessed by ultrasound. Endothelial function was evaluated in forearm resistance vessels and in the brachial artery by venous occlusion plethysmography and ultrasound imaging, respectively. Elevated levels of GDF-15 were related to several CV risk factors (male gender, current smoking, body mass index, waist circumference, diabetes, fasting glucose, triglycerides, and low HDL cholesterol). After adjustment for CV risk factors, increased levels of GDF-15 were associated with reduced endothelium-dependent vasodilation in resistance vessels, plaque burden, LV mass and concentric LV hypertrophy, reduced LV ejection fraction, and clinical manifestations of coronary artery disease and heart failure.

GDF-15 carries information on CV dysfunction and disease that is not captured by traditional CV risk factors in elderly individuals.

In 20 consecutive patients with congenital heart disease and RV to PA conduit obstruction, the following were prospectively assessed before and after percutaneous pulmonary valve implantation (PPVI): the septal curvature and LV volumes throughout the cardiac cycle by magnetic resonance imaging; RV to LV mechanical delay by 2D-echocardiographic strain imaging; and objective exercise capacity. Percutaneous pulmonary valve implantation led to a reduction in RV to LV mechanical delay (127.9 ± 50.9 vs. 37.7 ± 35.6 ms; P < 0.001) and less LV septal bowing in early LV diastole (septal curvature: –0.11 ± 0.11 vs. 0.07 ± 0.13 cm^–1; P < 0.001). Early LV diastolic filling (first one-third of diastole) increased significantly (17.5 ± 9.4 to 30.4 ± 9.4 mL/m²; P < 0.001). The increase in early LV diastolic filling correlated with the reduction in RV to LV mechanical delay (r = –0.68; P = 0.001) and change in septal curvature (r = 0.71; P < 0.001). In addition, the improvement in peak oxygen uptake (56.0 ± 16.0 vs. 64.1 ± 13.7% of predicted; P < 0.001) was associated with the increase in early LV diastolic filling (r = 0.69; P = 0.001).

Relief of RV to PA conduit obstruction significantly improves early LV filling properties. This is attributed to more favourable septal motion and reduction in interventricular mechanical delay.

Thirty consecutive patients with BrS were compared with 30 sex- (26/4 male/female), body surface area- (±0.2 m²), and age-matched (±5 years) normal volunteers. CMRI exam included long- and short-axis ECG-gated breath-hold morphological T1-TSE sequences for fatty infiltration and cine-SSFP sequences for kinetic assessment. Fatty infiltration was not found in any subject. Patients with BrS compared with normal subjects showed higher incidence of mild right ventricle (RV) wall-motion abnormalities [15 (50%) vs. 5 (17%) subjects (P = 0.006) with reduced radial fractional shortening in more than two segments], reduction of outflow tract ejection fraction (49 ± 11% vs. 55 ± 10%; P = 0.032), enlargement of the inflow tract diameter (46 ± 4 vs. 41 ± 5 mm, P < 0.001 in short-axis; 46 ± 4 vs. 42 ± 5 mm, P = 0.001 in four-chamber long-axis view) and area (22 ± 2 vs. 20 ± 3 cm²; P = 0.050), and of global RV end-systolic volume (34 ± 10 vs. 30 ± 6 mL/m²; P = 0.031) but comparable outflow tract dimensions, global RV end-diastolic volume, left ventricle parameters, and atria areas.

CMRI detects a high prevalence of mild structural changes of the RV, and suggests further pathophysiological complexity in BrS. Prospective studies to assess the long-term evolution of such abnormalities are warranted.

Atherectomy samples were stained with antibodies against glycophorin A (a protein specific to erythrocyte membranes), CD31, 4-HNE, and CD163. Quantitative analysis demonstrated that glycophorin A-positive areas, 4-HNE-positive macrophage score, and CD163-positive macrophage score in UAP patients were significantly higher (glycophorin A, P < 0.0001; 4-HNE-positive macrophage score, P < 0.0001; CD163-positive macrophage score, P < 0.0005) than in SAP patients. The percentage of the glycophorin A-positive area showed a significant positive correlation with the number of CD31-positive microvessels and the 4-HNE-positive macrophage score (microvessels, R = 0.59, P < 0.0001; 4-HNE, R = 0.59, P < 0.0001). Moreover, the CD163-positive macrophage score was positively correlated with glycophorin A-positive area and the 4-HNE-positive macrophage score (glycophorin A, R = 0.58, P < 0.0001; 4-HNE, R = 0.53, P < 0.0001).

These findings suggest a positive association among intraplaque haemorrhage, enhanced expression of Hb scavenger receptor, and lipid peroxidation in human unstable plaques.

The VALsartan In Acute myocardial iNfarcTion trial (VALIANT) enrolled 14 703 post-MI patients with left ventricular dysfunction and/or heart failure and followed them for a median of 24.7 months. In the present secondary analysis, times from baseline to first GI bleeding were identified from the VALIANT serious adverse event database. Potential risk factors were explored from medical history, demographics, clinical profile, and medications, both at baseline and during follow-up. We also explored the relationship between the occurrence of GI bleeding and subsequent mortality. During follow-up, 98 (0.7%) patients had a serious GI bleeding event. These patients were older, had more comorbidities, were more likely to be taking additional antiplatelet drugs, and had worse left ventricular systolic and renal function. The Kaplan–Meier estimated rate of GI bleeding at 6 months was 0.37% (95% CI 0.27–0.47). In a multivariable Cox model, dual antiplatelet therapy was the most powerful predictor of GI bleeding, with an adjusted hazard ratio of 3.18 (95% CI 1.91–5.29). Other predictors were non-white race, history of alcohol abuse, increasing age, worse New York Heart Association class, anticoagulant therapy, diabetes, lower estimated glomerular filtration rate, and male sex. Gastrointestinal bleeding was associated with increased risk of death [adjusted hazard ratio 2.54 (95% CI 1.66–3.89)].

Following MI, clinical characteristics can identify patients with increased risk of GI bleeding. The use of dual antiplatelet agents appears to be the most profound risk factor. Whether these patients would benefit from GI prophylaxis therapy remains unknown.

Hundred patients with recurrent episodes of classical VVS underwent two tilt tests in a randomized sequence. One test included 20 min of tilt at 60° with intravenous administration of 5 mg clomipramine (clomipramine tilt), whereas the other test included an initial 30 min period of passive 60° tilt, followed by sublingual spray administration of 400 µg nitroglycerin (nitroglycerin tilt). Fifty asymptomatic subjects served as controls. Following clomipramine tilt, a positive response occurred in 73 patients (73%), a negative response in 23 (23%), and drug intolerance in 4 (4%). With nitroglycerin tilt, these percentages were 52, 48, and 0%, respectively. Significant differences were observed regarding positive responses (clomipramine vs. nitroglycerin: 73/100 vs. 52/100, P < 0.05), as well as negative responses (23/100 vs. 48/100, respectively, P < 0.05). A high concordance rate was observed in positive responses.

In the evaluation of patients with recurrent classical VVS, clomipramine tilt is associated with an increased positive yield relative to nitroglycerin tilt. This suggests that central mechanisms may be more important than peripheral ones in VVS pathogenesis.

This randomized, double-blind, placebo-controlled study included 85 patients with myocarditis and chronic (>6 months) heart failure unresponsive to conventional therapy, with no evidence of myocardial viral genomes. Patients received either prednisone 1 mg kg^–1 day^–1 for 4 weeks followed by 0.33 mg kg^–1 day^–1 for 5 months and azathioprine 2 mg kg^–1 day^–1 for 6 months (43 patients, Group 1) or placebo (42 patients, Group 2) in addition to conventional therapy for heart failure. Primary outcome was the 6 month improvement in left-ventricular function. Group 1 showed a significant improvement of left-ventricular ejection fraction and a significant decrease in left-ventricular dimensions and volumes compared with baseline. None of Group 2 patients showed improvement of ejection fraction, that significantly worsened compared with baseline. No major adverse reaction was registered as a result of immunosuppression.

These data confirm the efficacy of immunosuppression in virus-negative inflammatory cardiomyopathy. Lack of response in 12% of cases suggests the presence of not screened viruses or mechanisms of damage and inflammation not susceptible to immunosuppression.

We compared PMNs apoptotic rate at 4 and 24 h in patients with UA, stable angina (SA), and controls (H) with two different protocols by flow cytometry. We measured apoptotic rate of isolated PMNs (Protocol 1) in 30 UA patients, 13 SA patients, and 34 H; and apoptosis of PMNs in whole blood culture (Protocol 2) in further 10 UA patients, 7 SA patients, and 6 H. Serum high-sensitivity C-reactive protein was also measured. Polymorphonuclear neutrophils of UA patients showed a decreased apoptotic rate compared with SA patients and H at 4 h in Protocol 1 (both P < 0.01), and at 24 h in Protocol 2 (P < 0.05 and <0.01, respectively). In overall population, a negative correlation was found between apoptotic rate at 4 h and high-sensitivity C-reactive protein levels (P < 0.01). Six among 40 patients with UA had early recurrence of symptoms and their apoptotic rate was significantly reduced compared with UA patients without recurrence of symptoms (P = 0.024).

Our study demonstrates delayed PMN apoptosis in UA. This alteration might be involved in the persistence of inflammatory activation and affects recurrence of instability.

We excluded individuals with mutations in genes currently associated with low HDL (ABCA1, LCAT, APOA-I, and SMPD1). We identified two patients in which cellular phospholipid efflux in the HDL biosynthesis process is impaired, whereas cholesterol efflux is normal. Two-dimensional gel electrophoresis analysis further showed that the two patients with impaired phospholipid efflux were defective primarily in the larger -HDL subpopulations. In fibroblasts from affected subjects, oxysterol stimulation resulted in increased ABCA1 protein expression and normalized their defective phospholipid efflux defect.

Our results indicate for the first time in humans that phospholipid and cholesterol efflux are two separate and distinct processes in cellular HDL biosynthesis. They further show for the first time that normal cellular phospholipid efflux is necessary for the formation of larger -HDL particles. The defect in phospholipid efflux is due to defective ABCA1 protein regulation and can be corrected by treatment with physiological oxysterols, a current therapeutic target of interest, that may, with further studies, be used to raise HDL levels in patients with severe HDL deficiencies.

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.

Of the 2708 advanced chronic systolic HF patients in the Beta-Blocker Evaluation of Survival Trial, 653 had a history of AF. Propensity scores for AF were calculated for each patient and were used to assemble a cohort of 487 pairs of patients with and without AF who were balanced on 74 baseline characteristics. Matched Cox regression analyses were used to estimate associations of AF with outcomes during 23 months of mean follow-up. All-cause mortality occurred in 187 (rate, 2046/10 000 person-years of follow-up) and 181 (rate, 1885/10 000 person-years) matched patients with and without AF, respectively [matched hazard ratio (HR) when AF was compared with no-AF 1.03, 95% confidence interval (CI) 0.79–1.33; P = 0.84]. Heart failure hospitalization occurred in 215 (rate, 3171/10 000 person-years) and 184 (rate, 2405/10 000 person-years) matched patients with and without AF, respectively (matched HR when AF was compared with no-AF 1.28, 95% CI 1.00–1.63; P = 0.049). Hazard ratios and 95% CIs for AF-associated HF hospitalization for bucindolol and placebo groups were, respectively, 1.08 (0.81–1.43) and 1.54 (1.17–2.03; P for interaction = 0.09).

A history of AF had no intrinsic association with mortality but was associated with HF hospitalization in chronic systolic HF.

In 10 consecutive patients, TTC was diagnosed by coronary angiography, ventriculography, and echocardiography. Endomyocardial biopsies were taken during the phase of severely impaired left ventricular (LV) function and after functional recovery. Non-diseased LV tissue from three donor hearts not used for transplantation served as healthy controls. Expression levels of Ca²⁺-regulatory proteins were analysed by means of real-time PCR, western blot, and immunohistochemistry. SLN, predominantly expressed in the atrial component, showed a remarkable ventricular expression in TTC patients. Gene expression of SERCA2a was significantly down-regulated. Conversely, PLN/SERCA2a ratio was increased. For PLN, dephosphorylation was documented using western blot and immunostaining of PLN-Ser¹⁶ and PLN-Thr¹⁷. No changes could be documented for NCX and RyR2.

In TTC, ventricular expression of SLN and dephosphorylation of PLN potentially result in a reduced SERCA2a activity and its Ca²⁺ affinity. Thus, the TTC is associated with specific alteration of Ca²⁺-handling proteins, which might be crucial for contractile dysfunction.

We sequenced the coding region of ANKRD1 from 231 independent DCM cases. We identified five missense mutations (three sporadic and two familial) absent from 400 controls and affecting highly conserved residues. Expression of the mutant CARP proteins after transfection in rat neonate cardiomyocytes indicated that most of them led to both significantly less repressor activity measured in a reporter gene assay and greater phenylephrin-induced hypertrophy, suggesting altered function of CARP mutant proteins.

On the basis of genetic and functional analysis of CARP mutations, we have identified ANKRD1 as a new gene associated with DCM, accounting for ~2% of cases.

Case–control study among 3510 acute myocardial infarction patients (without prior vascular disease, diabetes, or statin use) in UK hospitals and 9805 controls. Relative risks (age, sex, smoking, and obesity-adjusted) were more strongly related to apoB than to LDL-C and, given apoB, more strongly negatively related to apoA₁ than to HDL-C. The ratio apoB/apoA₁ was uncorrelated with time since symptom onset in cases, was reproducible in samples collected a few years apart in controls (correlation 0.81), and encapsulated almost all the predictive power of these four measurements. Its effect was continuous, substantial throughout the UK normal range [relative risk, top vs. bottom decile of this ratio, 7.3 (95% CI 5.8–9.2)] and varied little with age. The ratio apoB/apoA₁ was substantially more informative about risk (₁² = 550) than were commonly used measures such as LDL-C/HDL-C, total/HDL cholesterol, non-HDL cholesterol, and total cholesterol (₁² = 407, 334, 204, and 105, respectively). Given apoB and apoA₁, the relationship with risk of LDL-C was reversed, and this reversal was strengthened by appropriate allowance for random measurement errors in two correlated variables. Given usual apoB, lower LDL-C (consistent with smaller LDL particles) was associated with higher risk (P < 0.0001). During the first 8 h after symptom onset HDL-C increased by about 10%, precluding reliable assessment of the joint relationship of apoA₁ and pre-onset HDL-C with risk in such retrospective case–control studies.

Apolipoprotein ratios are more informative about risk than lipid fractions are. This suggests that, among lipoprotein particles of a particular type (LDL or HDL), some smaller and larger subtypes differ in their effects on risk. Direct measurements of even more specific subtypes of lipoprotein particles may be even more informative about risk.

Patients enrolled in a national registry were evaluated during a median follow-up of 16 months after CRT implant. Patients with valvular heart disease treated with CRT (n = 108) in comparison with ischaemic heart disease (n = 737) and dilated cardiomyopathy (n = 635) patients presented: (i) a higher prevalence of chronic atrial fibrillation, with atrioventricular node ablation performed in around half of the cases; (ii) a similar clinical and echocardiographic profile at baseline; (iii) a similar improvement of LVEF and a similar reduction in ventricular volumes at 6–12 months; (iv) a favourable clinical response at 12 months with an improvement of the clinical composite score similar to that occurring in patients with dilated cardiomyopathy and more pronounced than that observed in patients with ischaemic heart disease; (v) a long-term outcome, in term of freedom from death or heart transplantation, similar to patients affected by ischaemic heart disease and basically more severe than that of patients affected by dilated cardiomyopathy.

In ‘real world’ clinical practice, CRT appears to be effective also in patients with valvular heart disease. However, in this group of patients the outcome after CRT does not precisely overlap any of the two other groups of patients, for which much more data are currently available.

The long-term SES-SMART clinical study was a multicentre, prospective, randomized, single-blind study of 257 patients receiving a SES or BMS in a small coronary artery, who were evaluated at discharge, 30 days, 8 and 24 months after stenting. The clinical endpoint of the study was a 24 months composite of major adverse cardiac and cerebrovascular events, which included death, non-fatal myocardial infarction, ischaemia-driven target lesion revascularization (TLR), and cerebrovascular accident. The 24 months follow-up was completed by 254 patients (98.8%). The use of SES was associated with a significantly lower incidence of the clinical endpoint (12.6% vs. 33.1%; HR 0.30, 95% CI: 0.17–0.55; P < 0.0001), which was not only due to a reduction in TLR (7.9% vs. 29.9%; HR 0.30, 95% CI: 0.16–0.59; P < 0.0001), but also to a reduction in myocardial infarction (1.6% vs. 10.2%; HR 0.09, 95% CI: 0.01–0.66; P = 0.018).

In comparison with BMS, the use of SES in the percutaneous revascularization of small coronary arteries is associated with improved clinical outcomes after 2 years follow-up.

The survey promoted by the Italian Society of Invasive Cardiology on ULMCA stenosis was an observational study involving 19 high-volume Italian centres. We enrolled 1111 patients with ULMCA stenosis treated with DES. Major adverse cardiac events were defined as death, myocardial infarction, and target lesion revascularization. Three hundred and thirty-four patients had ostial or midshaft lesions (group 1) and 777 bifurcations (group 2). The adjusted hazards ratio of the risk of 2 year MACE of patients in group 2 vs. patients in group 1 was 1.50 (P = 0.024). However, we observed that there was a significant difference between patients with bifurcations treated with two stents and those in group 1 (P = 0.001), but not between patients with bifurcations treated with one stent and those in group 1 (P = 0.38).

Patients with bifurcations have a worse outcome than patients with ostial and midshaft lesions. However, the technique used to treat bifurcations has a significant impact on clinical outcomes.

Eighty-six patients with STEMI who had successfully undergone percutaneous coronary intervention (PCI) were randomized to receive intracoronary injection of BMMNC (n = 41) or saline (n = 45). Left ventricular ejection fraction, as evaluated by UCG, was markedly improved at 6 months (0.484 ± 0.5 vs. 0.457 ± 0.6, P = 0.001), 1 year (0.482 ± 0.7 vs. 0.446 ± 0.6, P < 0.001), and 4 years (0.505 ± 0.8 vs. 0.464 ± 0.8, P < 0.001) after BMMNC transplant when compared with control group. However, the current cell therapy did not improve the myocardial viability of the infarcted area as assessed by single-photon emission computed tomography analysis at 4 years post-transplant (0.263 ± 0.007 in BMMNC group vs. 0.281 ± 0.008 in control group, P = 0.10). During the follow-up period, one control group case (2.2%) of in-stent restenosis was confirmed by coronary angiography and underwent repeat PCI. Also during follow-up, one death (2.2%) occurred in the control group, and one patient (2.4%) in the BMMNC group had transient acute heart failure.

This study indicates that intracoronary delivery of autologous BMMNC is safe and feasible for STEMI patients who have undergone PCI, and can lead to long-term improvement in myocardial function.

Forty-two consecutive patients with first-time ST-elevation MI, single-vessel disease, successfully treated with primary percutaneous coronary intervention (PCI) were included. Microvascular obstruction, infarct size, and LV remodelling were assessed by cardiac magnetic resonance. Cardiac magnetic resonance was performed at: 2 days, 1 week, 2 months, and 1 year following PCI. Microvascular obstruction was assessed by first-pass perfusion. Patients were divided into three groups according to the presence or absence of MO at 2 days and 1 week: no detectable MO at any time point (11 patients), MO detectable only at 2 days (16 patients), and MO detectable both at 2 days and 1 week (15 patients). In multivariable analysis adjusting for infarct size at 2 days, detectable MO at 1 week was an independent predictor (P = 0.003) of infarct size at 1 year follow-up, associated with adverse infarct healing, adverse LV remodelling, increased LV volumes, and lower ejection fractions when compared with the rest of the cohort.

Microvascular obstruction is an important determinant of infarct healing. The effect of MO on infarct size translated into distinct patterns of LV remodelling during long-term follow-up.

Clinical study no.: NCT 00465868

We studied 5745 ST-segment elevation myocardial infarction patients treated with primary percutaneous coronary intervention (PCI) in APEX-AMI. Approximately 11% had AF during hospitalization. Atrial fibrillation prevalence at baseline and at discharge was 4.8% [confidence interval (CI) 4.3–5.4%] and 2.5% (CI 2.1–2.9%), respectively. The proportion of 5466 patients without AF at baseline who developed new onset AF was 6.3% (CI 5.6–6.9%). This corresponded to 9.3 cases of new onset AF/1000 patient days at risk. New onset AF was independently associated with 90 day mortality [adjusted hazard ratio (HR) 1.81; 95% CI 1.06–3.09; P = 0.029] after accounting for baseline covariates and in-hospital procedures and complications. New onset AF was associated with shock (adjusted HR 3.81; 95% CI 1.88–7.70; P = 0.0002), congestive heart failure (adjusted HR 2.66; 95% CI 1.74–4.06; P < 0.0001), and stroke (adjusted HR 2.98; 95% CI 1.47–6.04; P = 0.0024) in models accounting for baseline covariates. Of AF patients, 55% did not receive oral anticoagulation therapy at discharge. Among patients with coronary stents, 5.1% were discharged on triple therapy. Patients at highest risk of stroke (CHADS₂ score ≥2) were least likely to receive oral anticoagulation at discharge (39%). Warfarin use in patients with AF at discharge (43.4%) was associated with lower rates of 90 day mortality and stroke.

Atrial fibrillation prevalence at baseline and at discharge was 4.8 and 2.5%, respectively. The proportion of patients who developed new onset AF was 6.3%. New onset AF was independently associated with 90 day mortality and was a marker of adverse outcomes in patients undergoing primary PCI.

Using positron emission tomography, resting and hyperaemic (adenosine, 140 µg/kg/min) myocardial blood flow (MBF) was measured in 25 patients with systemic lupus erythematosus (SLE) or rheumatoid arthritis (RA). Coronary flow reserve (CFR) was calculated as adenosine/resting MBF. Patients had normal or minimally diseased (i.e. ≤20% luminal diameter) coronary arteries at angiography and no cardiovascular risk factors. Twenty five age- and gender-matched healthy volunteers served as controls. Resting MBF was similar in patients and controls (1.25 ± 0.27 vs. 1.15 ± 0.24 mL/min/g; P = 0.15) while patients had lower hyperaemic MBF (2.94 ± 0.83 vs. 4.11 ± 0.84 mL/min/g; P < 0.001) and CFR (2.44 ± 0.78 vs. 3.81 ± 1.07; P < 0.001). CFR was inversely related to disease duration (r = –0.65; P < 0.001) and SLE disease activity (r = –0.69; P = 0.01). Seven patients showed ischaemic electrocardiographic changes during adenosine. They had longer disease duration (21 ± 7 vs. 14 ± 5 years; P = 0.03) and lower CFR (1.76 ± 0.81 vs. 2.49 ± 0.54; P = 0.006) when compared with patients without changes.

A reduced CFR in the absence of significant coronary disease is suggestive of CMD. We speculate that this is the consequence of prolonged systemic inflammation, which may precede and contribute to premature coronary artery disease in these patients.

Thirty-seven obese adults were examined before and 18 months after bariatric surgery. Carotid intima–media thickness (CIMT), brachial flow-mediated dilation (FMD), nitroglycerine-mediated dilation, and abdominal fat distribution were assessed by high-resolution ultrasound. Surgery resulted in a body mass index decrease of 9.1 ± 4.9 kg/m² with concomitant improvements in glucose and lipid metabolism. Carotid intima–media thickness diminished from 0.56 ± 0.09 to 0.53 ± 0.08 mm (n = 37; P = 0.004). Flow-mediated dilation improved from 5.81 ± 3.25 to 9.01 ± 2.93% (n = 25; P < 0.001). Both CIMT and FMD were associated with intra-abdominal fat diameter.

The present results demonstrate that bariatric surgery-induced diminution of visceral fat improves both functional and structural markers of early atherosclerosis, providing a link between the weight loss-associated improvements of traditional and non-traditional risk factors and the reduced long-term morbidity and mortality after bariatric surgery.

A total of 60 patients (mean age 21 ± 10 years; 35 females) with congenital heart disease underwent pulmonary valve replacement with homograft insertion and were prospectively enrolled into a study protocol that included serial echocardiography and CMR 1 year after surgery. None of the patients had homograft stenosis but 10 (17%) had significant homograft incompetence (i.e. pulmonary regurgitation fraction >20% on CMR). A higher incidence of ‘eccentric’ pulmonary forward flow pattern (P < 0.001, Fisher's exact test), more acute ‘homograft distortion angle’ (P < 0.001), larger relative ‘annular’ size (P < 0.01), and greater pre-homograft right ventricular outflow tract (RVOT) diameters (P = 0.01) at CMR was seen in those with worse homograft function. In a backward multivariate linear regression model, ‘eccentric’ pulmonary forward flow pattern (r_part = 0.36, P < 0.001), ‘homograft distortion angle’ (r_part = 0.31, P = 0.001), and pre-homograft RVOT diameter (r_part = 0.19, P = 0.03) were independently associated with the degree of pulmonary regurgitation (in %) at 1 year.

Using CMR, in this prospective cohort study, we have shown that significant valve incompetence is present in one-sixth of patients after homograft insertion into the pulmonary position, and that alterations in the in situ homograft geometry were associated with the likelihood of developing valve incompetence. These findings imply that mechanical factors may have an important impact on homograft performance.

A cohort of 101 consecutive patients with high risk for embolic events and indication for implant/replacement of a pacemaker/ICD were randomized to two anticoagulant strategies: bridging from OAC to heparin infusion (n = 51) vs. maintenance of OAC to reach an INR = 2 ± 0.3 at the day of the procedure (n = 50). Haemorrhagic and thrombo-embolic complications were evaluated at discharge, 15 and 45 days after the procedure. A total of 4/51 patients (7.8%) from heparin group and 4/50 (8.0%) from the OAC group developed pocket haematoma following the implant (P = 1.00). One haematoma in each group required evacuation (1.9 vs. 2%, P = 1.00). No other haemorrhagic events or embolic complications developed during the follow-up. Duration of the hospital stay was longer in the heparin group [median of 5 (4–7) vs. 2 (1–4) days; P < 0.001].

Implant of devices maintaining OAC is as safe as bridging to heparin infusion and allows a significant reduction of in-hospital stay.

A total of 813 patients were enrolled in CARE-HF. Baseline log-transformed NT-proBNP independently predicted all-cause mortality, sudden death, and death from pump failure. In a multivariable model including log-transformed NT-proBNP, assignment to CRT remained independently associated with better prognosis without evidence of interaction. Stratifying patients according to the median NT-proBNP and to CRT treatment allocation, all-cause mortality was 12% if <median + CRT, 25% if <median + control group, 35% if ≥median + CRT, and 51% if ≥median + control group. There was no evidence of a difference in the relative effect of CRT across different values of NT-proBNP.

NT-proBNP retains its prognostic value in HF patients with CRT. Deploying CRT before the patients have reached end-stage HF may maximize the benefit of treatment.

A cross-sectional study of chronic kidney disease (CKD) and peripheral arterial disease (PAD) in 3089 adult participants aged 40+ from the 1999–2002 National Health and Nutrition Examination Survey (NHANES). Kidney function, assessed by estimated glomerular filtration rate (eGFR), was determined from serum creatinine and cystatin C using established equations. Peripheral arterial disease defined by an ankle brachial index <0.90. Glomerular filtration rate estimated using cystatin C was more strongly associated with PAD compared with eGFR using serum creatinine before and after multivariable adjustment. Further, after adjustment for cystatin C, kidney function based on serum creatinine was no longer significantly associated with PAD. However, cystatin C remained significantly associated with PAD even after adjustment for GFR estimated by serum creatinine. Compared with optimal kidney function (eGFR_{serum creatinine} ≥60, eGFR_{cystatin C} >90), the odds ratio for PAD was 3.11 (95% confidence interval 1.26–7.64) for preclinical CKD (eGFR_{serum creatinine} ≥60, eGFR_{cystatin C} <76.7) and 5.07 (3.01–8.52) for ‘confirmed’ CKD (eGFR_{serum creatinine} <60, eGFR_{cystatin C} <60).

Chronic kidney disease was strongly and independently associated with PAD. Cystatin C was a more potent marker of lower extremity PAD when compared with the serum creatinine equation currently used in clinical practice. Our results suggest that cystatin C may have clinical utility when combined with serum creatinine in evaluation of individuals who may have PAD.

Patients, free of coronary artery disease, were divided into β–_HFNEF (n = 16), β+_HFNEF (n = 16), β–_HFREF (n = 17), and β+_HFREF (n = 22) groups. Using LV endomyocardial biopsies, we assessed collagen volume fraction (CVF) and cardiomyocyte diameter (MyD) by histomorphometry, phosphorylation of myofilamentary proteins by ProQ-Diamond phosphostained 1D-gels, and expression of β-adrenergic signalling and calcium handling proteins by western immunoblotting. Cardiomyocytes were also isolated from the biopsies to measure active force (F_active), resting force (F_passive), and calcium sensitivity (pCa₅₀). Myocardial effects of β-blocker therapy were either shared by HFNEF and HFREF, unique to HFNEF or unique to HFREF. Higher F_active, higher pCa₅₀, lower phosphorylation of troponin I and myosin-binding protein C, and lower β₂ adrenergic receptor expression were shared. Higher F_passive, lower CVF, lower MyD, and lower expression of stimulatory G protein were unique to HFNEF and lower expression of inhibitory G protein was unique to HFREF.

Myocardial effects unique to either HFNEF or HFREF could contribute to the dissimilar outcome of β-blocker therapy in both HF phenotypes.

Thirty-two patients (59 ± 11 years) after first MI (Pats_MI), 10 patients (63 ± 10 years) with LBBB (ejection fraction < 40%; Pats_LBBB<40), 13 patients (63 ± 11) with LBBB (ejection fraction ≥ 40%; Pats_LBBB≥40), and 15 healthy controls (53 ± 10 years) underwent 3D tagging CMR and LGE imaging at 1.5 T. As a measure of mechanical LV dyssynchrony, the standard deviation of T_max over the LV, the circumferential uniformity ratio estimate (CURE) index, and a segmental-based circumferential systolic dyssynchrony index (SDI) were calculated. All three parameters detected significantly increased circumferential dyssynchrony in patients compared with controls. The CURE and SDI showed a good correlation (r = 0.93, P < 0.0001) and detected most severe dyssynchrony in Pats_LBBB<40 (P < 0.001 vs. controls, P < 0.005 vs. Pats_MI). Systolic dyssynchrony index additionally allowed integration of localized viability information to yield SDI_viable which was highest in Pats_LBBB<40.

Dyssynchrony patterns in the LV can be quantified globally and regionally by 3D tagging CMR. Combination of viability and dyssynchrony information allows for a comprehensive dyssynchrony quantification in patients with LBBB or post-MI. Future studies are required to test the value of the method to predict responsiveness to resynchronization.

Pre-procedural HDL-C levels and post-procedural peak cTnI levels were collected in 350 patients undergoing PCI. Data were analysed for PMI and for acute myocardial infarction (AMI) during follow-up. Patients with PMI (n = 115) had lower HDL-C levels than patients without PMI [n = 235; 1.17 mmol/L (0.75–2.51) vs. 1.27 mmol/L (0.70–2.87), P < 0.001]. Pre-procedural HDL-C levels were inversely related to the occurrence of PMI [odds ratio for PMI: 0.884, 95% CI: 0.80, 0.98; P = 0.02 for an HDL-C-increment of 5 mg/dL (0.13 mmol/L)] and to AMI during follow-up [hazard ratio (HR): 0.697, 95% CI: 0.54, 0.90; P = 0.005]. The occurrence of PMI was associated with an elevated HR for AMI (4.702, 95% CI: 1.79, 12.37; P = 0.002). Low-risk levels of pre-procedural HDL-C [men ≥40 mg/dL (≥1.03 mmol/L), women ≥45 mg/dL (≥1.16 mmol/L)] did not influence the negative effects of PMI on outcome (HR: 5.510, 95% CI: 1.43, 21.31; P = 0.013) and reduction of AMI-free survival [mean AMI-free survival time with PMI: 1167.5 days (95% CI: 1098.27, 1236.67) vs. 1240.7 days (95% CI: 1220.94, 1290.49) without PMI; log-rank P = 0.005].

Small increases in HDL-C in patients undergoing elective PCI convert into a substantial reduction of risk for PMI, which has adverse effects on the long-term prognosis. Patients with PMI are at a high risk for AMI at any HDL-C level and therefore should receive particular monitoring by the treating physician over a long period after PCI.

In this pilot study, automated external defibrillators (AEDs) were provided to all 43 fire stations in Stockholm during 2005. Fire-fighters were dispatched in parallel with traditional emergency medical responders (EMS) to all suspected cases of OHCA. Additionally, 65 larger public venues were equipped with AEDs. All 863 OHCA from December 2005 to December 2006 were included during the intervention, whereas all 657 OHCA from 2004 served as historical controls. Among dual dispatches, fire-fighters assisted with cardiopulmonary resuscitation (CPR) in 94% of the cases and arrived first on scene in 36%. The median time from call to arrival of first responder decreased from 7.5 min during the control period to 7.1 min during the intervention (P = 0.004). The proportion of patients in shockable rhythm remained unchanged. The proportion of patients alive 1 month after OHCA rose from 4.4 to 6.8% [adjusted odds ratio (OR): 1.6; 95% confidence interval (CI): 0.9–2.9]. One-month survival in witnessed cases rose from 5.7 to 9.7% (adjusted OR: 2.0; 95% CI: 1.1–3.7). Survival after OHCA in the rest of Sweden (Stockholm excluded) declined from 8.3 to 6.6% during the corresponding time period (unadjusted OR: 0.8; 95% CI: 0.6–1.0). Only three OHCA occurred at public venues equipped with AEDs.

An introduction of a dual dispatch early defibrillation programme in Stockholm has shortened response times and is likely to have improved survival in patients with OHCA, especially in the group of witnessed cardiac arrests. The increase in survival is believed to be associated with improved CPR and shortened time intervals.