Design: Prospective, single center, cohort study.

Setting: A 1900-bed tertiary-care university hospital in Seoul, Korea

Design and patients: The predictive power of NT-proBNP, CRP, and Revised Cardiac Risk Index (RCRI) for the risk of PMCE (myocardial infarction, pulmonary edema, or cardiovascular death) were evaluated from a prospective cohort of 2054 elective major noncardiac surgery patients. Optimal cut-off values were derived from receiver operating characteristic curve (ROC) analysis.

Main outcome measurement: PMCE (myocardial infarction, pulmonary edema, or cardiovascular death) within postoperative 30 days.

Results: PMCE developed in a total of 290 patients (14.1%). Each increasing quartile of NT-proBNP or CRP level was associated with a greater risk of PMCE after adjustment for traditional clinical risk factors. The relative risk (RR) of highest versus lowest quartile was 5.2 for NT-proBNP (p<0.001) and 3.7 for CRP (p<0.001). Both NT-proBNP (cut-off = 301 ng/L) and CRP (cut-off = 3.4 mg/L) predicted PMCE better than RCRI (cut-off = 2) by ROC analysis (p<0.001). Moreover, the predictive power of RCRI (adjusted RR = 1.5) could be improved significantly by addition of CRP and NT-proBNP to RCRI (adjusted RR = 4.6) (p<0.001).

Conclusions: High preoperative NT-proBNP or CRP is a strong and independent predictor of perioperative major cardiovascular event in non-cardiac surgery. The predictive power of current clinical risk evaluation system would be strengthened by these biomarkers.

Design: A multi-centre, double blind randomised controlled trial

Setting: Selection from emergency room, geriatric medicine and orthopaedic departments.

Patients: Patients over 50 years, with 2 unexplained falls +/- one syncopal event in the previous 12 months for which no other cause is evident apart from CICSH.

Interventions: Patients randomised to either a 700/400 Kappa, rate responsive pacemaker or implantable loop recorder (Medtronic Reveal thera RDR, Medtronic, mineapolis, Minnesota).

Main outcome measures: The primary outcome was the number falls post implant. Secondary outcomes were time to fall event, presyncope, quality of life and cognitive function.

Results: 141 patients were recruited from 22 centres. Mean age was 78 years and mean follow up 24 months. The overall relative risk of falling after device implant compared with before was 0.23 (0.15-0.32). No significant falls reduction was observed between paced and loop recorder groups (RR 0.79; 95% CI: 0.41, 1.50). Data was also consistent in both groups for syncope, quality of life and cognitive function.

Conclusions: These results question the use of pacing in CICSH and are at variance with our seminal paper. We note, however, that the study was underpowered and also patient characteristics differed from the SAFEPACE 1 - participants were physically and cognitively frailer. Further work is necessary to assess cardiac pacing in this setting.

Objective: Analyze genes previously associated to heterotaxy in order to assess mutations in familial TGA unassociated with other features of laterality defects.

Methods: Probands of 7 families with isolated TGA and family history of concordant or discordant CHDs were screened for mutations in the ZIC3, ACVR2B, LEFTYA, CFC1, NODAL, FOXH1, GDF1, CRELD1, GATA4 and NKX2.5 genes.

Results: Mutation analysis allowed the identification of 3 sequence variations in 2 out of 7 TGA probands. A FOXH1 (Pro21Ser) missense variant was found in a proband who was also heterozogous for an amino acid substitution (Gly17Cys) in ZIC3 gene. This ZIC3 variant was also found in another family member with a second sequence variation (Val150Ile) in the NKX2.5 gene homeodomain who was affected by multiple ventricular septal defects. A second proband was found to harbor a splice site variant (IVS2-1G>C) in NODAL gene.

Conclusions: The present study provides evidence that some cases of familial TGA are caused by mutations in laterality genes and thereby are part of the same disease spectrum of heterotaxy syndrome, and argues for an oligogenic or complex mode of inheritance in these pedigrees.

Objective: To evaluate the ability of Dual Source CT (DSCT) to quantify noncalcified plaque volumes using intravascular ultrasound (IVUS) as the standard of reference.

Methods: We analyzed the datasets of 70 patients with suspected or known coronary artery disease who underwent DSCT (330 ms gantry rotation, 2 x 64 x 0.6 mm collimation, 60 – 90 mL contrast agent) prior to invasive coronary angiography, with IVUS performed as part of the diagnostic procedure. One hundred individual noncalcified coronary atherosclerotic plaques (1 to 3 plaques per patient) with suitable fiducial markers were matched and selected for plaque volume measurements using manual segmentation. Only DSCT data sets with good or excellent image quality were considered for analysis.

Results: Intra- and interobserver variability for plaque volume measurements by DSCT were 6 ± 5% and 11 ± 7%, respectively. Mean total plaque volume by DSCT was 89 ± 66 mm3 (range, 14 to 400 mm3). Mean total plaque volume by IVUS was 90 ± 73 mm3 (range, 16 to 409 mm3). The mean difference between DSCT and IVUS was 1 ± 34 mm3 (range, -131 to 85 mm3). Despite the good correlation for plaque volume measurements (r = 0.89, P < 0.001), agreement between the two methods was only modest (Bland Altman limits of agreement, -67 to +65 mm3).

Conclusions: Noncalcified plaque volumes as determined by DSCT yielded good correlation but only modest agreement in comparison to IVUS.

Design: Randomised, placebo-controlled, double-blind study (sub-study of FINCELL).

Setting: Two tertiary cardiac centres.

Participants: 78 patients with STEMI randomly assigned to receive either intracoronary BMC (n=39) or placebo (n=39) into the infarct related artery.

Interventions: Thrombolysis a few hours after symptom onset, PCI and intracoronary injection of BMC two to six days later.

Main outcome measures: Efficacy of the BMC treatment was assessed by measurement of the change of global left ventricular ejection fraction (LVEF) from baseline to six months after STEMI. Various pre-defined variables (e.g. the levels of certain natriuretic peptides and inflammatory cytokines) were analyzed as determinants of improvement of LVEF.

Results: In the BMC group, the most powerful determinant of the change of LVEF was the baseline LVEF (r = -0.58, p<0.001). Patients with baseline LVEF at or below median (≤62.5%) experienced a more marked improvement of LVEF (+12.7 ± 12.5 %units, P<0.001) than those above median (-0.8 ± 6.3 %units, p=0.10). Elevated N-terminal probrain natriuretic peptide (P<0.001) and N-terminal proatrial natriuretic peptide (P=0.052) levels were also associated with improvement of LVEF in the BMC group but not in the placebo group.

Conclusions: The global LVEF recovers most significantly after intracoronary infusion of BMCs in patients who have the most severe impairment of LVEF on admission. The baseline levels of natriuretic peptides seem also to be associated with LVEF recovery after BMC treatment.

The association between alcohol consumption and Coronary Heart Disease (CHD) has been broadly studied. Most studies conclude that moderate alcohol intake reduces the risk of CHD. There are many discussions on whether the association is causal or biased. The objective is to analyse the association between alcohol intake and risk of CHD in the Spanish cohort of the European Prospective Investigation into Cancer (EPIC).

Methods

Participants from the EPIC Spanish cohort were included (15,630 men and 25,808 women). The median follow up period was 10 years. Ethanol intake was calculated using a validated dietary history questionnaire. Participants with a definite CHD event were considered cases. A Cox regression model was performed adjusted for relevant covariables and stratified by age. Separate models were carried out for men and women.

ResultsCrude incidence rate of CHD was 300.6/100,000 person-years for men and 47.9/100, 000 person-years for women. Moderate, high and very high consumption was associated with a reduce risk of CHD in men: HR 0.86 (95% CI= 0.54-1.38) for former drinkers, 0.64 (95% CI= 0.4-1.0) for low, 0.47 (95% CI= 0.31-0.73) for moderate, 0.45 (95% CI= 0.29-0.69) for high and 0.49 (95% CI= 0.28-0.86) for very high consumers. In women a negative association was found with p values above 0.05 in all categories.

ConclusionsIn men aged 29-69 years, alcohol intake was associated with a more than 30% lower CHD incidence. Our study is based on a large prospective cohort study and is free of the abstainer error.

Methods and results: The study included consecutive 192 patients with APE, (79M/113F, 64±18yrs) and 100 controls matched for age, sex and concomitant diseases. On admission blood samples were collected for MPV and troponin measurements. Although MPV did not differ between APE and controls (10.0±1.2 vs.10.1±0.8fl), it differed between low and intermediate or high risk APE (9.4±1.2fl, 10.3±1.1fl, 10.3±1.8 fl; respectively, p<0.0001). Eighteen (9%) APE patients died during 30-day observation. MPV was higher in non-survivors than survivors (10.7±1.4fl vs. 9.9±1.2fl, p<0.01). The areas under ROC curves of MPV were 0.658(95%CI:0.587-0.725) for predicting 30-day mortality, and 0.712(95%CI:0.642-0.775) for 7-day mortality. MPV>10.9fl, showed sensitivity, specificity, PPV and NPV for death within 30 days (39%,81%,18%,93%, respectively) and for 7-day mortality (54%, 82%, 18%, 96%). Multivariable analysis revealed MPV was the independent mortality predictor for 7- and 30-day all-cause mortality (HR 2.0[CI95%:1.3-3.0, p<0.001] and 1.7[CI95%:1.2-2.5, p<0.01], respectively). MPV were higher in patients with myocardial injury than in those without troponin elevation (10.2±1.1fl vs. 9.8±1.2fl; p=0.02). There were correlations between MPV and right ventricle (RV) diameter and RV dysfunction (r=0.28,p<0.01 and r=0.19,p<0.02, respectively).

Conclusion: MPV is an independent predictor of early death in APE. Moreover, MPV in APE is associated with right ventricular dysfunction and myocardial injury.

Objectives: To analyze the clinical and microbiological profile of patients with blood culture negative early prosthetic valve endocarditis ("BCN early PVE") in order to define the most appropriate empiric treatment.

Design, setting and participants: From June 2001 to February 2009, a prospective multimodal strategy incorporating serological, molecular and histopathological assays was performed in all the samples referred to our laboratory for a suspicion of blood culture negative endocarditis from France and abroad (n=718). A total of 31 patients with "BCN early PVE" were identified. Their microbiological profile was compared with that of 22 patients with blood culture positive early prosthetic valve endocarditis ("PBC early PVE") and 628 patients with "Community-acquired BCNE" identified during the same period.

Results: A pathogen was identified in 10 patients (32%) with "BCN early PVE". Fungi were the most common pathogens identified being found in 16% versus 4.5% in case of "PBC early PVE" and 0.5% in "Community-acquired BCNE" (p<0.0001). The global microbiological profile of "BCN early PVE" differed strongly from that of "PBC early PVE" and "Community-acquired BCNE". A higher rate of microbiological diagnosis was obtained in patients who underwent surgery (9/21 [43%] versus 1/10 [10%], p=0.07) and an increased rate of recurrences was observed when a pathogen could not be identified (9/21 [43%] versus 1/10 [10%], p=0.07).

Conclusions: "BCN early PVE" exhibit specific aetiologies as fungi are the most frequent pathogens identified. Therefore, we suggest investigating fungi particularly by molecular methods on surgical specimen and that an antifungal drug might be added to the empiric treatment.

Design: Case-control study.

Patients: 418 stable CAD patients, 54 of whom were treated with PPIs. All patients were treated with non-enteric coated aspirin 75 mg/day and received no other antithrombotic drugs.

Main outcome measures: Platelet aggregation was measured by Multiplate^® whole blood aggregometry induced by arachidonic acid 1.0 mmol/L and expressed as area under the aggregation curve (Aggregation Units*min). Platelet activation was assessed by soluble serum P-selectin. Compliance was confirmed by serum thromboxane B₂ levels.

Results: The distribution of age, sex, body mass index, blood pressure, family history of ischaemic heart disease, smoking, diabetes, and the number of previous ischaemic events did not differ between groups. All patients were compliant with aspirin therapy according to serum thromboxane B₂ levels. Platelet aggregation (median 180 (interquartile range 119-312) vs. 152 (84-226) Aggregation Units*min, p = 0.003) and soluble serum P-selectin levels (88.5 (65.2-105.8) vs. 75.4 (60.0-91.5) ng/mL, p = 0.005) were significantly higher in patients treated with PPIs. Furthermore, these patients had significantly higher serum thromboxane B₂ levels (geometric mean 1.29 (95% confidence interval 0.96-1.72) vs. 0.92 (0.84-1.01) ng/mL, p = 0.011).

Conclusions: CAD patients treated with PPIs had a reduced platelet response to aspirin in terms of increased residual platelet aggregation and activation compared with CAD patients not taking PPIs. Concomitant use of aspirin and PPIs might reduce the cardiovascular protection by aspirin.

We present a review of the randomized controlled trial evidence examining the role of these three agents in acute coronary syndromes, and provide recommendations for the practicing physicians of their optimal use in clinical practice.

Methods: A total 167 patients with hospitalized heart failure (age 65 ±12, ejection fraction < 35%) were followed prospectively. Using tissue Doppler imaging (TDI), the time to peak systolic velocity during the ejection phase was measured in the basal septal and lateral segments. A temporal difference between the septal to lateral wall (Ts-l) of 65 msec or more was defined as a mechanical dyssynchrony.

Results: After 33 months of follow up, 70 patients (41.9%) had cardiac events including 42 (25.1%) cardiac death. The event free survival time decreased as Ts-l or QRS duration increased. Patients with QRS ≥120 msec had increased risks of cardiac events by multivariate Cox proportional hazard analysis (HR 1.85, 95% CI 1.05 - 3.24, p = 0.032). The presence of mechanical dyssynchrony also predicted an increased risk of cardiac events (HR 2.35, 95% CI 1.37 - 4.01, p = 0.002). Those with both electrical and mechanical dyssynchrony had a HR of 3.98 (95% CI 2.02 - 7.86, p < 0.001) when compared to those with normal QRS duration and absence of mechanical dyssynchrony. The addition of mechanical dyssynchrony significantly improved the prognostic power of a model containing echocardiographic parameters and QRS duration.

Conclusions: TDI-derived mechanical dyssynchrony is an important prognosticator and independently associated with QRS duration in predicting adverse events in patients with systolic heart failure.

Methods: In 20 patients with chronic stable coronary artery disease (CAD), the hypothesis was tested that ECP augments collateral function during a 1-minute coronary balloon occlusion. Before and after 30 hours of randomly allocated ECP (20 90-minute sessions over 4 weeks at 300mmHg inflation pressure) or sham ECP (same setting at 80mmHg inflation pressure), invasive collateral flow index (CFI, no unit) was obtained in 34 vessels without coronary intervention. CFI was determined by the ratio of mean distal coronary occlusive to mean aortic pressure both subtracted by central venous pressure. Additionally, coronary collateral conductance (occlusive myocardial blood flow per aorto-coronary pressure drop) was determined by myocardial contrast echocardiography, and brachial artery flow-mediated dilation (FMD) was obtained.

Results: CFI changed from 0.125 (0.073; interquartile range) at baseline to 0.174 (0.104) at follow-up in the ECP group (p=0.006), and from 0.129 (0.122) to 0.111 (0.125) in the sham ECP group (p=0.14). Baseline to follow-up change of coronary collateral conductance was from 0.365 (0.268) to 0.568 (0.585)ml/min/100mmHg in the ECP group (p=0.072), and from 0.229 (0.212) to 0.305 (0.422) ml/min/100mmHg in the sham ECP group (p=0.45). There was a correlation between the FMD change from baseline to follow-up and the corresponding CFI change (r=0.584, p=0.027).

Conclusions: ECP appears to be effective in promoting coronary collateral growth. The extent of collateral function improvement is related to the amount of improvement in systemic endothelial function.

Patients and design: Twenty patients with low workload myocardial ischemia underwent, in a randomized cross-over study, 2 treadmill exercise stress tests (ESTs) in 2 separate days: 1) a single maximal EST (EST-1), and 2) a maximal EST (EST-2) performed 45 minutes after a low-workload EST stopped at 1 mm ST depression (p-EST). Platelet reactivity was evaluated by measuring the closure time (CT) in response to ADP/collagen by the PFA-100 method, and monocyte–platelet aggregate (MPA) formation and CD41 platelet expression, with and without ADP stimulation, by flow cytometry.

Results: Compared to resting values, CT decreased at peak EST-1 (p<0.001) but not at peak EST-2. MPA after ADP stimulation increased more significantly at peak EST-1 compared to peak EST-2 (p<0.001). Repetition in 7 patients of the pEST/EST-2 protocol after intravenous administration of the adenosine antagonist theophylline showed prevention of the effects of p-EST on exercise induced platelet reactivity.

Conclusions: A short episode of myocardial ischemia induces protection against exercise induced increase of platelet reactivity. Our data also suggest a role for adenosine in this phenomenon.

Methods: From June 2008 to June 2009 consecutive patients with symptomatic severe aortic valve stenosis (area < 1 cm²), age ≥ 75 years with a logistic EuroSCORE ≥ 15% or age > 60 years plus additional specified risk factors were evaluated for TAVI.

Examinations of study patients were performed before and 30 days after TAVI and comprised assessment of quality of life (Minnesota living with heart failure questionnaire, [MLHFQ]) six-minute walk test, measurement of B-type natriuretic peptide and echocardiography. Aortic valve prosthesis was inserted retrograde using a femoral arterial or a subclavian artery approach.

Results: In 44 consecutive patients (mean age of 79.1 ± 7 years, 50% women, mean left ventricular ejection fraction 55.8 ± 8.5%) TAVI was successfully performed. Follow-up 30 days after TAVI showed a significantly improved quality of life (baseline 44 ± 19.1 vs. 28 ± 17.5 MLHFQ Score, p < 0.001) and an enhanced distance in the six-minute walk test (baseline 204 ± 103 vs. 266 ± 123 meters, p < 0.001). B-type natriuretic peptide levels were reduced (baseline 725 ± 837 vs. 423 ± 320 pg/mL, p = 0.005).

Conclusions: Our preliminary results show a significant clinical benefit and a reduction of neurohormonal activation in patients with severe and symptomatic aortic valve stenosis early after TAVI.

Methods: All NICM patients receiving primary prevention ICDs (non-CRT) from 2005-present at our institutions were studied. Patients had NIDCM confirmed by a lack of significant stenoses on coronary angiography, a lack of valvular abnormalities on echo, and LV dysfunction with EF<35%. Patients had to have a diagnosis of NIDCM for >9 months and be on optimal medical therapy for >3 months prior to implant. All patients had >NYHA II symptoms. Baseline and follow-up EF was documented by quantitative echo and/or MUGA scan.

Results: 332 patients were identified via a database search. Patients were 67±11 years, 75% male, NYHA 2.3±0.7, with EF 25±13%, and LV diastolic diameter 61±10 mm. Time from initial NIDCM diagnosis to implant was 11±6 months and duration of medical therapy pre-implant was 8±5 months. Therapy at the time of implant included ACE-inhibitors or ARBs (85%), beta-blockers (77%), spironolactone (53%), loop diuretic (63%), and digoxin (50%). Repeat EF assessment was available in 309/332 (93%) 8±6 months post-implant. EF improved to >35% in 37/309 (12%) patients. Patients who improved had a shorter time from diagnosis to implant (9±3 vs 13±5 months respectively, p=0.03). No other predictors were identified for patients with improved EF.

Conclusions: A substantial number of patients (12%) with NIDCM experience improvement in LV function to above levels recommended for ICD implant. A shorter time from diagnosis to implant may predict post-implant improvement.

Design: Prospective cohort study.

Patients and methods: In 191 consecutively recruited males with HF (mean age, 64 years; New York Heart Association [NYHA] class I-IV 24/35/35/6%) and reduced (ejection fraction [EF] ≤40%, n=96) or preserved left ventricular function (EF>40%, n=95) total and free serum testosterone, dehydroepiandrosterone sulfate (DHEAS), and sex hormone binding globulin (SHBG) were measured. The median observation period was 859 days.

Results: During follow-up 53 patients (28%) died. While total serum testosterone was normal in most patients (91%), free testosterone and DHEAS were reduced in 79% and 23%, respectively. DHEAS and free testosterone, but not total testosterone, were inversely associated with NYHA class (both P<0.01). Lower free testosterone and DHEAS and higher SHBG predicted all-cause mortality risk (hazard ratio[HR] 0.89, 95% confidence interval[CI] 0.82-0.96 per 1 ng/dl free testosterone, P=0.004, HR 0.95, 95% CI 0.89-1.00, per 10 µg/dl DHEAS, P=0.058, and HR 1.18, 95% CI 1.05-1.33 per 10 nmol/l SHBG, P=0.006, respectively [adjusted for age and NYHA class]). However, further adjustment for carefully selected confounding factors abolished these associations.

Conclusion: In male HF patients, low serum levels of androgens are associated with adverse prognosis, but this relation is confounded by indicators of a poor health state. Our results suggest that low serum androgens develop as a sequel of this progressive multi-faceted systemic disorder.

Methods and results: OCT was used to measure the fibrous cap thickness of coronary artery atherosclerotic plaques in patients with acute myocardial infarct (AMI), unstable angina pectoris (UAP) and stable angina pectoris (SAP). Plasma levels of inflammatory factors including highly sensitive C-reacting proteins (hs-CRP), interleukin-18 (IL-18), and tumor necrosis factor-alpha (TNF-) were detected by enzyme linked immunosorbent assay (ELISA); and peripheral white blood cell (WBC) counts were performed. Our results demonstrated that the plasma levels of inflammatory factors and WBC count were correlated inversely with fibrous cap thickness (r = -0.775 for hs-CRP, r = -0.593 for IL-18, r = -0.60 for TNF-, and r = -0.356 for WBC count). Patients with cap thickness < 65 µm [defined to be thin-cap fibroatheromas (TCFA)] had higher plasma levels of inflammatory factors as well as WBC count than those with thicker fibrous caps. Receiver operator curves for hs-CRP, IL-18, TNF- and WBC count, which displayed the capability of prediction about TCFA showed the area under the curves were 0.95, 0.86, 0.79 and 0.70 (P<0.05), respectively. ROC curve analysis confirmed that an hs-CRP cut-off at 1.66 mg/L would detect TCFA with a sensitivity of 96% and a specificity of 90%, and was the strongest independent predictor for TCFA.

Conclusion: There is an inverse linear correlation between fibrous cap thickness and plasma levels of inflammatory markers. The plasma hs-CRP concentration is the strongest independent predictor for TCFA.

Methods and results: Patients (NYHA III-IV) scheduled for mitral annuloplasty (n=9) or ventricular restoration (n=10) and patients with normal left ventricular function undergoing CABG (n=12) were instrumented with pressure-conductance catheters to measure pressure-volume loops pre- and post-surgery. Data obtained during vena cava occlusion provided directly-measured EDPVRs. Baseline end-diastolic pressure (Pm) and volume (Vm) were used for single-beat prediction of EDPVRs. Root-mean-squared-error (RMSE) between measured and predicted EDPVRs, was 2.79±0.21mmHg. Measured vs. predicted end-diastolic volumes (EDV) at pressure levels 5, 10, 15 and 20mmHg showed tight correlations (R2: 0.69-0.97). Bland-Altman analyses indicated overestimation at 5mmHg (bias: pre-surgery 44mL (95% CI: 29 to 58mL); post-surgery 35mL (23 to 47mL)) and underestimation at 20mmHg (bias: pre-surgery -57mL (-80 to -34mL); post-surgery -13mL (-20 to -7.0mL)). EDVs were significantly different between groups and between conditions, but these differences were not dependent on the method (i.e. measured vs. predicted). RMSEs were not different between groups or conditions, nor dependent on Vm or Pm, indicating that EDPVR prediction was equally accurate over a wide volume range.

Conclusions: Single-beat EDPVRs obtained from hearts spanning a wide range of sizes and conditions accurately predicted directly-measured EDPVRs with low RMSE. Single-beat EDPVR indices correlated well with directly-measured values, but systematic biases were present at low and high pressures. The single-beat method facilitates less invasive EDPVR estimation, particularly when coupled with emerging noninvasive techniques to measure pressures and volumes.

Screening for vascular disease implies that there should be an effective treatment for those identified that leads to better outcomes than in those detected and treated later. Introducing such screening programmes will inevitably preferentially select the affluent, thus increasing social inequalities.

Population-wide health protection measures need supplementation with targeted screening programmes for those at particular risk. We cannot afford to continue to funnel more and more money into wider screening for diseases caused by lifestyle without also dealing with the population-level causes of those lifestyles. Equally, the continuing polarised debate in preventive health must not ignore those at the highest risk that need targeting and treatment today, whilst continuing in parallel to strive to find underlying remedies for their high risk.

The aim of the study was to evaluate whether primary percutaneous coronary intervention (PCI) with combined proximal embolic protection and thrombus aspiration results in smaller final infarct size (IS) and improved left ventricular function (LVF) assessed by cardiovascular magnetic resonance (CMR) in ST-segment elevation myocardial infarction (STEMI) patients compared with primary PCI alone.

One of the more recent developments in the field is three-dimensional echocardiography (3DE). 3DE, in various forms, has been used as a research tool for many years now, but lately improvements in software and transducer technology have begun to facilitate its integration into clinical practice. As with any technique, 3DE has its strengths and weaknesses and these must be fully appreciated if it is to be utilised effectively.

To compare magnetic resonance myocardial perfusion imaging (MRI) to anatomical assessment with multi-slice computed tomography coronary angiography (MSCT) and conventional coronary angiography.

Evaluate the association of physical activity with LV structure and function in the general population in a community setting.

Left ventricular hypertrophy (LVH) confers high cardiovascular risk. Regression of LVH reduces risk. Patients with blood pressure in the normal range and LVH are common. We investigated whether further reduction in blood pressure would further regress LVH.

LV apical rotation significantly contributes to LV twist, which has been reported to play a vital role in maintaining LV systolic and diastolic function. Apical hypertrophic cardiomyopathy(ApHCM) is a unique disease with pathologic LV hypertrophy at the apex. We aimed; 1) to evaluate LV twist mechanics in ApHCM and 2) to demonstrate the influence of predominantly local, pathologic involvement of the apical myocardium on LV twist mechanics.

To study whether vascular function assessment using flow-mediated constriction (L-FMC), a novel non-invasive method, complements the information obtained with "traditional" flow-mediated dilation (FMD).

Reduced exercise capacity in diabetics has been attributed to limitations in cardiac function and microvascular dysfunction leading to impaired supply and nutritive perfusion to exercising muscles.

Imaging of coronary plaques has traditionally focused on evaluating degree of stenosis, as the risk for adverse cardiac events increases with stenosis severity. However, the relation between plaque composition and severity of stenosis remains largely unknown.

To investigate long term safety and efficacy after intracoronary injection of autologous mononuclear bone marrow cells (mBMCs) in acute myocardial infarction (AMI).

To determine the effect of education and other measures of socioeconomic status (SES) on risk of acute myocardial infarction (AMI) in patients and controls from countries of diverse economic circumstances (high, middle, and low income countries).

Objective: In this prospective follow-up study we investigated whether the Type D personality construct (the tendency to experience negative emotions and to be socially inhibited) exerts an independent effect on disease-specific health status in post-myocardial infarction (MI) patients, after adjustment for disease severity and depressive symptoms.

Methods: Patients (n=503) were assessed on demographic and clinical variables and completed the Type D Scale (DS14) and Beck Depression Inventory (BDI) within the first week of hospital admission for acute MI. Two months post-MI, all patients completed the CIDI interview. After 18-months, they filled out the Seattle Angina Questionnaire (SAQ) to assess disease-specific health status.

Results: At follow-up, Type D patients had significantly lower mean scores on all SAQ subscales, indicating worse disease-specific health status, as compared to non-Type D patients (all p-values <0.01). After adjustment for disease severity and depression in multivariate analysis, Type D patients still had more physical limitations (mean SAQ score: 49 versus 54; p=0.014), less angina stability (62 versus 71; p=0.002) and a less accurate disease perception (52 versus 61; p=<0.001) compared with non-Type D patients. Depressed patients (BDI≥10) also reported significantly lower SAQ scores compared to non-depressed patients.

Conclusions: The Type D construct is an independent predictor of impaired disease-specific health status. Type D personality, in addition to depression, may thus be an important psychological factor that deserves attention during the period of rehabilitation in post-MI patients.

Background: Few reports described outcomes of complete compared with infarct related artery (IRA) only revascularization in patients with ST elevation myocardial infarction (STEMI) and multivessel coronary disease (CAD). Moreover there are no studies comparing simultaneous treatment of non-IRAs with the IRA treatment followed by elective procedure for the other lesions (staged revascularization).

Methods: We studied the outcomes of 214 consecutive patients with STEMI and multivessel CAD undergoing primary angioplasty. Before the first angioplasty patients were randomized to 3 different strategies: 1) culprit vessel angioplasty only (COR group), 2) staged revascularization (SR group), and 3) simultaneous treatment of non-IRAs (CR group).

Results: During a mean follow-up of 2.5 years, 42 (50.0%) patients in COR group experienced at least one major adverse cardiac event (MACE), 13 (20.0%) in SR group, and 15 (23.1%) in CR group, p<0.001. In-hospital death, repeat revascularization and re-hospitalization occurred more frequently in COR group (all p<0.05), while there was no significant difference in re-infarction among the 3 groups. Survival free of MACE was significantly reduced in COR group but it was similar in CR and SR groups.

Conclusions: Culprit vessel only angioplasty was associated with the highest rate of long-term MACE as compared to multivessel treatment. Patients scheduled for staged revascularization experienced a similar rate of MACE as patients undergoing complete simultaneous treatment of non-IRAs.

Primary percutaneous coronary intervention (PPCI) is now considered the optimal approach to the management of myocardial infarction with ST-segment elevation when the procedure is performed expeditiously and at a high-volume centre (1-3).

The complex contextual elements that influence communication of risk to patients present challenges for physicians, particularly in high-risk situations. This editorial reflects on the findings by Aase et al regarding risk communication and the associated and relatively unexplored existential issues.

Transcatheter aortic valve implantation (TAVI) offers considerable promise in treating patients with aortic stenosis (AS) who are at high risk with conventional aortic valve replacement (AVR). Selection criteria for TAVI are clinical and anatomical. As this technology is still new, manufacturers play an important role in validating patient anatomical criteria in relation to prosthesis specification (label information).

Assessment of anatomical variables is very detailed. Attention needs to be paid to precise measurement of annular dimensions. Imprecise sizing brings risk of misplacement, embolization, aortic regurgitation, aortic rupture, tamponade, or need for postdilatation or 2nd valve in valve. Recommended annular dimensions should be followed as strictly as possible, especially as longer term results of suboptimal implant are uncertain. Detailed assessment of other parameters such as the vasculature and distance to the coronary ostia should also be made.

Assessment of clinical risk and suitability for TAVI should be by multidisciplinary team (MDT). The team should consist of cardiac surgeons, imaging and interventional cardiologists and a cardiac anaesthetists. Risk can by defined by patient factors present (age being the most common but not exclusive one ) and significant co-morbidities, and assessment of the "potential to improve" post procedure should also be made. For frailty and general patient assessment involvement of a geriatrician is desirable. Local results for surgical AVR should also be considered. This is good clinical practice, while evidence is being built via RCT and registries. Currrent criteria are neither too strict or lax, but appropriate for a novel technology with a limited evidence base.

Data from COURAGE have led to renewed criticism of PCI practice levelled at the perceived lack of outcome benefit compared with optimal medical therapy. However, the interpretation of COURAGE can be dependent upon individual bias and there is a balance to be struck based upon robust data that defends PCI as an effective treatment for stable coronary disease, provided the therapy is ischaemia-directed

There is substantial evidence that emotional stress can trigger acute cardiac events in vulnerable individuals.^{1 2} Most research on emotional triggers has involved retrospective interviews with survivors of acute myocardial infarction, asking them about the circumstances surrounding the onset of their illness, but in addition the impact of natural or human disasters has been studied. Investigations of major events such as earthquakes have the advantages that a population-based sampling methodology can be used, that the timing of stimuli can be defined objectively instead of relying on self-report, and that the incidence of cardiac events can be contrasted with levels during nontraumatic comparison periods. The first set of thorough analyses was conducted in the wake of the Northridge earthquake that took place in January 1994 in the Los Angeles area. There was an abrupt increase in sudden cardiac deaths immediately after the earthquake,³ together with a rise in coronary heart disease mortality that were not observed for other cardiovascular diseases or non-cardiac causes.⁴ Deaths typically occurred among people with advanced coronary atherosclerosis. Acute physiological responses such as autonomic dysfunction and inflammatory, neuroendocrine and platelet activation, coupled with disruption of vulnerable plaque, may be responsible for the onset of acute infarction in these circumstances.⁵ One study of survivors of acute myocardial infarction measured the physiological responses to a standardised mental stress test in patients whose cardiac event had apparently been triggered by emotional stress, in comparison with those who reported no stress before their infarction.⁶ The emotional trigger group showed more prolonged blood pressure responses to standardised stress, together with heightened blood platelet activation, suggesting that they had a particular proclivity to respond with physiological responses that might contribute to cardiac vulnerability.

Background: Anecdotal evidence suggests that transcatheter aortic valve implantation (TAVI) is being used beyond pre-market label indications.

Methods: To assess the frequency and outcomes associated with "off-label" use of TAVI, we conducted a retrospective study, examining adherence to patient selection criteria in 63 patients undergoing implantation with the 18F CoreValve ReValving^TM System (CRS). Label status (on- vs. off-label) was determined by following 1) inclusion/exclusion criteria indicated in the 18F CRS safety and efficacy trial and 2) a patient selection matrix indicating anatomical boundaries to guide patient selection. Off-label use was defined as the presence of at least one exclusion criteria or "non-acceptable" criteria based on the patient selection matrix.

Results: Off-label implantation was identified in 42 patients (67%) - 40% had one, 19% had two, and 8% had three or more off-label criteria. Baseline demographics were similar between the groups except for a higher logistic EuroSCORE in the on-label group (19.8±11.2 vs. 14.5±7.3, p=0.029). There was no significant difference in the procedural success rates between the on- and off-label groups (91 vs. 95%, respectively, p=0.47). The frequency of angiographic moderate-severe aortic regurgitation, post-implant dilatation or implantation of a second valve was also similar between the groups. At 30 days, the cumulative death rate was 10%; there were four deaths in the "on-" and three deaths in the off-label group.

Conclusion: In this study we found that "off-label" implantation of the CRS was common. Further studies are needed to evaluate the consequences of "label status" for patients undergoing TAVI.

Objectives: We report comprehensive clinical, echocardiographic and prospective computerised tomography (CT) follow-up data following stenting for aortic coarctation from a single centre.

Background: Stenting for aortic coarctation is known to be effective in the medium term. Aneurysm formation following stent implantation is a recognized complication. However, data regarding aortic wall injury and stent integrity following stent placement are sparse.

Methods: Full data analysis of all patients undergoing balloon expandable stent implantation and follow up procedures in a single tertiary congenital cardiac unit.

Results: Between October 2002 and April 2008, we performed 102 coarctation stent procedures ( 94 stents, 88 patients) . Median age was 20.6 years (range 8.5-65) and median weight 65Kgs (range 34-101). Twelve procedures were re-dilatations. Stenting resulted in reduction of coarctation gradient from a median of 20 to 4mm Hg. There were no procedure related deaths. Four patients had immediate complications During median follow-up of 34.5 months (range 4.2-72.8), 2 patients had late complications requiring additional stent procedures. Follow-up CT data are available in 84 patients with MRI in one patient (96.5%). Only 1 patient developed a procedure related aortic aneurysm. All stent fractures (n=7) occurred with a single stent design.

Conclusions: Stenting for aortic coarctation and recoarctation is effective with low immediate complication rates. Computerized tomography is useful in the longer term for assessment of stent integrity and post-procedural aneurysm formation. Overall incidence of post-procedural aneurysm is rare and stent fractures were not seen with newer generation stents.

Objective: To compare out of hospital cardiac arrest (OOHCA) characteristics in White and South Asian populations within Greater London.

Methods: Data for OOHCAs were extracted from 1st April 2003 to 31st March 2007. Primary study variables included age, gender, ethnicity, response times from 999 call to ambulance arrival, initial cardiac rhythm, whether bystander CPR was provided prior to arrival of the London Ambulance Service NHS Trust (LAS) crew, whether the arrest was witnessed (bystander or LAS crew) and hospital outcome including survival to hospital admission and discharge.

Results: Of 13,013 OOHCAs of presumed cardiac cause 3161 (24.3%) had ethnicity codes assigned. These comprised of 63.1% (n=1995) White and 5.8% (n=183) South Asian people with the remaining from other backgrounds. White patients were on average five years older than South Asians (69.5 Vs 64.6, p<0.005). Response time (7.48 mins Vs 7.46 mins), bystander CPR (34.4% versus 29.7%), initial cardiac rhythm (29.5% versus 30.4%), and survival to admission (22.2% versus 22.5%) and discharge (8.7% versus 8.9%) were comparable between the two ethnic groups. South Asians were slightly more likely to have a witnessed OOHCA compared to their White counterparts (OR 1.1, 95% CI 1.0–1.2).

Discussion: The quality of care provided was comparable between White and South Asian populations. The data support the emerging view that South Asians’ high mortality from CHD reflects higher incidence rather than higher case fatality. South Asian had OOHCA at a significantly younger age. The study demonstrates the importance of ethnic coding within the emergency services.

The right ventricular apex (RVA) has been the elective site for placing endocardial pacing leads since 1959 when Furman described the use of the transvenous route for pacemaker implantation. This site was used because it is easily accessible, readily identified, and associated with a stable position and reliable chronic pacing parameters. It was recognised however, that pacing from the RVA did not reproduce normal ventricular conduction or contraction. With the advent of reliable active fixation leads, alternative right ventricular sites became accessible and began to be explored. In this review, we will outline the detrimental effects of RVA pacing, define the right ventricular outflow tract, and discuss the evidence for selective site pacing.

Every year more than a million cardiac arrests are documented in the industrialized nations of the world, with the majority occurring in settings outside of the hospital. A major factor in survival after out-of-hospital cardiac arrest (OHCA) is early institution of bystander resuscitation efforts. Sadly, the majority of OHCA do not receive bystander resuscitation for a variety of reasons. One of them is the requirement for mouth-to-mouth (MTM) ventilation. The 2008 American Heart Association recommendation for "Hands Only" or continuous chest compression cardio pulmonary resuscitation (CPR) for untrained lay individuals was a welcome change. However, there is evidence to indicate that mouth-to-mouth and other forms of positive pressure ventilation should be eliminated for all bystanders responding to primary cardiac arrest (unexpected witnessed collapse in an unresponsive person). The requirement for MTM ventilation may well be indicated for patients with respiratory arrest but is detrimental during early resuscitation efforts by anyone providing CPR to patients with primary cardiac arrest. This article provides rationale for continuous chest compression CPR by all bystanders.

Background: Cardiovascular primary prevention should be targeted at those with the highest global risk. However, it is unclear how best to identify such individuals from the general population. The aim of this study was to compare mass and targeted screening strategies in terms of effectiveness, cost effectiveness and coverage.

Methods: The Scottish Health Survey provided cross-sectional data on 3,921 asymptomatic members of the general population aged 40-74 years. We undertook simulation models of five screening strategies: mass screening, targeted screening of deprived communities, targeted screening of family members, and combinations of the latter two.

Results: To identify one individual at high risk of premature cardiovascular disease using mass screening required 16.0 people to be screened at a cost of £370. Screening deprived communities targeted 17% of the general population but identified 45% of those at high risk, and identified one high-risk individual for every 6.1 people screened at a cost of £141. Screening family members targeted 28% of the general population but identified 61% of those at high risk, and identified one high-risk individual for every 7.4 people screened at a cost of £170. Combining both approaches enabled 84% of high risk individuals to be identified by screening only 41% of the population. Extending targeted to mass screening identified only one additional high-risk person for every 58.8 screened at a cost of £1,358.

Conclusions: Targeted screening strategies are less costly than mass screening, and can identify up to 84% of high-risk individuals. The additional resources required for mass screening may not be justified.

Background: Cardiac dilatation is associated with impaired pump function, progression of heart failure and electrical instability. Risk of sudden death is associated with a low blood level of n-3 polyunsaturated fatty acids.

Objective: The hypothesis was, therefore, addressed that left ventricular dilatation as assessed by echocardiography is associated with a reduced serum polyunsaturated fatty acid level.

Methods: Fatty acids were determined with gas chromatography/mass spectrometry in serum of 308 patients with dilative heart failure unrelated to myocardial infarction (Age 48±12 years, NYHA class 2.2±0.6, ejection fraction 31±10%).

Results: The extent of left ventricular dilatation as assessed by left ventricular enddiastolic diameter was associated with a reduction of both n-3 and n-6 polyunsaturated fatty acids. The n-3 docosahexaenoic acid (1.0±0.5% vs. 1.3±0.6%, P<0.001) and the n-6 arachidonic acid (4.6±1.8% vs. 5.2±1.9%, P<0.01) were reduced in patients with left ventricular dilatation (enddiastolic diameter, 68-90 mm, upper tertile vs. 48-61 mm, lower tertile). By contrast, monounsaturated fatty acids were increased (the n-9 oleic acid 26.1±4.8% vs. 23.9±4.8%, P<0.01). A low docosahexaenoic acid (0.01-0.9%, lower tertile vs. 1.4-3.1%, upper tertile) was associated with greater left ventricular dilatation (enddiastolic diameter, 67±8 vs. 63±7 mm, P<0.001). The cut-off for the absence of severe dilatation (enddiastolic diameter >70 mm) was set at >1.24% docosahexaenoic acid. In our sample, the negative predictive value for severe dilatation was 91% and sensitivity was 84%.

Conclusions: Docosahexaenoic acid provides a new sensitive biomarker for monitoring and detecting severe left ventricular dilatation in heart failure patients.

Aims: To quantify right ventricular (RV) function in patients with chronic thromboembolic pulmonary hypertension (CTEPH) before and after pulmonary endarterectomy (PEA).

Methods: Out of 33 patients included, 16 were evaluated clinically and with echocardiography (conventional and myocardial deformation parameters) before PEA (preop) and at 1week, 1month, 3months and 6months after PEA. RV fractional area change (RVFAC), tricuspid annular plane systolic excursion (TAPSE) as well as mid-apical and basal peak ejection strain (S) and strain rate (SR) of the RV free wall were measured. Left ventricular (LV) apical lateral wall motion was regarded as indicating changes in overall heart rocking motion (RM). Heart catheterization was performed before, within 1 week and at 6months after PEA.

Results: Clinical and hemodynamic parameters improved significantly after PEA. This correlated with the improvement in RVFAC, S and SR. TAPSE, on the other hand, showed a biphasic response (14.5±4mm preop, 8.5±2.7mm at 1w and 11±1.5mm at 6m). Changes in LV apical motion explain this finding: At baseline, TAPSE was enhanced by rocking motion of the heart due to the failing RV. Unloading the RV by PEA normalized the rocking motion and TAPSE decreased.

Conclusions: RV function of CTEPH patients improves steadily after PEA. Unlike S, SR and RVFAC, this is not reflected by TAPSE due to postoperative changes in overall heart motion. Motion independent deformation parameters (S, SR) appear superior in the accurate description of regional RV function.

Atrial fibrillation (AF) is the most common arrhythmia encountered in clinical practice. Despite the common association of AF with cardiovascular disease, some patients can be classified as ‘lone AF’. The latter is essentially a diagnosis of exclusion, and should be preceded by careful evaluation, including thorough collection of medical history, physical examination, blood pressure measurement, laboratory tests, ECG, echocardiography and possibly, chest x-ray and exercise testing. Lone AF patients were initially thought to have a good prognosis with respect to thromboembolism and mortality, compared with the general AF population, but more recent data suggest otherwise.

This review focuses on the clinical epidemiology and management aspects of lone AF, as well as various associated novel risk factors, such as familial, genetic and socioeconomic factors, alcohol, sports activity and biochemical markers.

Real time perfusion (RTP) echocardiographic imaging with a continuous infusion of microbubbles has improved the sensitivity of dobutamine stress echocardiography (DSE) in detecting coronary artery disease (CAD). The impact of RTP on treadmill exercise stress echocardiography (TESE) is unclear. To examine this, RTP was utilized in 254 DSE and TESE patients being examined for the presence of significant CAD over the same time period. A continuous infusion of 3% Definity (Lantheus Medical Imaging; North Billerica, MA) was used for all studies, and contrast replenishment (MCR), plateau intensity (PMCE) and wall motion (WM) were examined for the detection of CAD. For DSE, the sensitivity of myocardial perfusion (MP) imaging with RTP was 85%, which was significantly higher than WM analysis (72%; p<0.05). The improvement in sensitivity with MP analysis during DSE was primarily due to better detection of left anterior descending disease. MP sensitivity during TESE was significantly better than MP sensitivity during DSE (98% versus 85%; p<0.05), and WM sensitivity during TESE was better than WM sensitivity during DSE (89% versus 72%; p<0.05). The improvement in WM sensitivity during TESE was due to detection of subendocardial wall thickening abnormalities in 48% of the patients with induced subendocardial perfusion defects. In conclusion, myocardial perfusion imaging with RTP improves the detection of CAD during both DSE and TESE. During TESE, the subendocardial perfusion defects improve WM sensitivity by delineating subendocardial WM abnormalities.

Objective: To assess LV strain and displacement and their relations to LV geometry in patients with AS.

Design: Cross-sectional echocardiographic study in patients with aortic stenosis (AS). Peak circumferential, radial and longitudinal strain and radial, longitudinal and transverse displacement were measured by 2D-speckle tracking. Severity of AS was assessed from energy loss index (ELI). LV hypertrophy was present if LV mass/height2.7 ≥46.9/ 49.2 g/m2.7 in women/men and concentric LV geometry if relative wall thickness >0.43. LV geometry was assessed from LV mass/height2.7 and relative wall thickness in combination.

Setting: Department of Heart Disease, Haukeland University Hospital, Bergen, Norway.

Patients: 70 patients with AS (mean age 73±10 years, 54% women).

Interventions: None.

Main outcome measures: Association of regional and average LV myocardial strain and displacement with LV geometric pattern and degree of AS.

Results: Average longitudinal strain was lower in the hypertrophy groups and correlated with higher LV mass index and relative wall thickness, lower stress-corrected midwall shortening and smaller ELI (all p <0.05). Average strain and displacement in other directions did not differ between geometric groups. In multivariate regression analysis, lower average longitudinal strain was associated with higher relative wall thickness (β =0.15), lower EF (β =-0.16), systolic blood pressure (β =-0.16) and energy loss index (β =-0.20) (all p <0.05) (R² =0.72). Replacing relative wall thickness with LV mass, lower longitudinal strain was also associated with higher LV mass (β =0.21, p <0.05) (R2 =0.73).

Conclusions: In patients with AS, lower average longitudinal strain is related to higher LV mass, concentric geometry and more severe AS.

Background: Recent studies of patients with heart failure and of patients under intensive care indicate that digoxin may increase mortality if the patient has atrial fibrillation (AF).

Aim: To study which patients receive digoxin treatment for AF and what the prognosis is for patients given this treatment.

Method: 2824 patients with AF was studied prospectively for a mean of 4.6 years. Information about medication was obtained from the local hospital registry. Information about diagnoses, hospitalisations and deaths was obtained from national registries. Propensity score matching and Cox regression was used to account for confounding.

Results: Factors associated with digoxin use were permanent AF (Hazard Ratio (HR) 3.2, confidence interval (CI) 2.7-3.9), absence of pacemaker (HR 2.2, CI 1.6-3.0), history of heart failure (HR 2.0, CI 1.7-2.5), treatment at an Internal Medicine ward rather than a Cardiology ward (HR 1.6, CI 1.3-2.0), female sex (HR 1.6, CI 1.3-1.9) and age ¡Y80 years (HR 1.4, 1.1-1.7).

More patients with than without digoxin died (51% vs. 31%, p<0.0001). After adjustment for covariates, however, no disadvantages related to digoxin use could be found regarding all-cause mortality, myocardial infarction , ischemic stroke, time to readmission to hospital or days at hospital/year at risk. The only endpoint significantly associated with digoxin use was pacemaker implantations which were more common in digoxin treated patients (HR 2.0, CI 1.2-3.4).

Conclusion: Digoxin is mainly given to an elderly and frailer subset of AF-patients and is thus associated with an increased mortality. When differences in patient characteristics are accounted for digoxin use appears to be neutral regarding mortality and major cardiovascular events in AF patients.

Objective: To investigate whether hyper-lipoproteinemia(a) [Lp(a)] promotes coronary atherosclerosis, acute thrombosis resulting in myocardial infarction (MI), or both.

Design: Retrospective chart review.

Setting: A community-based general geriatric hospital.

Patients: 1,062 consecutive autopsy cases (609 men, 453 women). The mean age at the time of death was 80 years.

Main outcome measures: A semiquantitative evaluation of the coronary stenosis on cut sections and pathological definition of MI. Lp(a) levels of fresh serum taken antemortem, measured by a latex-enhanced turbidimetric immunoassay.

Results: The prevalence of severe coronary stenosis and pathological MI increased linearly with increasing Lp(a) levels with no apparent threshold. The odds ratios (95% C.I.) of hyper-Lp(a) [2.99 (1.70 - 5.28) for 200 - 299 mg/L and 3.25 (1.90 - 5.54) for > 300 mg/L] for severe coronary stenosis were larger than those of hypertension [2.61 (1.88 - 3.63)], diabetes mellitus [2.09 (1.41 - 3.11)], and hypercholesterolaemia [2.05 (1.31 - 3.21)]. The severe coronary sclerosis was much stronger risk of MI [6.28 (4.33 - 9.11)] than hyper-Lp(a), hypertension, and diabetes mellitus. A path analysis showed that the Lp(a) levels affected both coronary sclerosis and MI, with path coefficients of 0.15 and 0.07 (direct effect), respectively. In cases with severe coronary sclerosis, Lp(a) affected only MI (0.15).

Conclusions: Lp(a) levels have distinct effects on coronary sclerosis and MI, with about half of the overall effect on MI being via coronary sclerosis. This result supports the prothrombotic and a probable proinflammatory role of Lp(a) in coronary events.

Background: Dobutamine stress magnetic resonance (DSMR) imaging represents an excellent imaging approach for the detection of coronary artery disease (CAD). However, most studies predominantly reported the utility of DSMR in men. Thus, we performed a comparative study to evaluate the diagnostic value of DSMR in men and women.

Methods and results: High dose dobutamine/atropine stress magnetic resonance imaging was performed and evaluated regarding new or worsening wall motion abnormalities in 745 consecutive patients (204 women, 541 men). Invasive coronary angiography was performed within 30 days and served as the reference standard (≥70% stenosis). DSMR was technically successful and had diagnostic image quality in all patients except 2 women and 5 men (P=ns). In the absence of ischemia target heart rate was not reached in 9.3% of women and 8.5% of men (P ns) despite maximum pharmacologic infusion (1% and 2.2%, respectively, P=ns) or due to limiting side effects (8.3% and 6.3%, respectively, P=ns). Diagnostic values (sensitivity/specificity/accuracy) for the detection of significant coronary stenoses were similar for men (86%/83%/85%) and women (85%/86%/85%). There was no gender-based difference in regional diagnostic accuracy of DSMR for all 3 coronary vascular territories in patients with single-vessel CAD (81% vs. 81%, P=ns, respectively).

Conclusion: The diagnostic capability of DSMR regarding the detection of hemodynamically relevant, obstructive CAD is gender-independent.

Background: The extent of clopidogrel-mediated platelet inhibition varies considerably from one individual to the next. Numerous studies have shown that low responders suffer significantly more adverse events after coronary stenting than patients who respond well to antithrombotic treatment with clopidogrel. Dihydropyridine calcium-channel blockers (CCBs) inhibit the cytochrome P450 3A4 enzyme, which metabolizes clopidogrel to its active form. We therefore sought to investigate the influence of CCBs on clopidogrel-mediated platelet inhibition.

Methods: ADP-inducible platelet reactivity was assessed by light transmission aggregometry (LTA) and the VerifyNow P2Y12 assay in 162 patients after percutaneous intervention with stent implantation. Results in the fourth quartiles of both assays were considered as high-on treatment residual ADP-inducible platelet reactivity.

Results: Patients with concomitant CCB therapy showed a significantly higher on-treatment platelet reactivity than patients without CCB medication (p = 0.001 for both assays). Further, high on-treatment residual ADP-inducible platelet reactivity was significantly more common among patients currently taking CCBs (p = 0.001 for LTA and p = 0.004 for the VerifyNow P2Y12 assay). A multivariate regression analysis confirmed CCB treatment as an independent predictor of reduced clopidogrel-mediated platelet inhibition (p = 0.006 for LTA and p = 0.004 for the VerifyNow P2Y12 assay).

Conclusion: CCBs decrease clopidogrel-mediated platelet inhibition in patients undergoing angioplasty and stenting for cardiovascular disease.

Background: The seventh Committee on "Biological effects of Ionizing Radiation" (BEIR VII, 2006) underlines "the need of studies of infants who are exposed to diagnostic radiation because catheters have been placed in their hearts".

Objective: To determine the Lifetime Attributable Risk (LAR) of cancer associated with the estimated cumulative radiological dose in 59 children (42 males, age=2.8±3.2 years) with complex CHD, and to assess chromosomal DNA damage after cardiac catheterization procedures.

Methods: In all patients, the cumulative exposure was estimated as effective dose in milliSievert (mSv), and LAR cancer was determined from BEIR VII report. In a subset of 18 patients (13 males, age: 5±2± 5.7 years) micronucleus (MN) as biomarker of DNA damage and long-term risk predictor of cancer was assayed before and 2 hours after catheterization procedures. Dose–area product (DAP; Gy cm2) was assessed as measure of patient dose.

Results: The median life time cumulative effective dose was 7.7 mSv per patient (range 4.6-41.2 mSv). Cardiac catheterization procedures and computed tomography were responsible for 95% of the total effective dose. For a 1-year-old child, the LAR cancer was 1 in 382 (25^th-75^th percentiles 1 in 531-1 in 187) and 1 in 156 (25^th-75^th percentiles 1 in 239-1 in 83) for male and female patients, respectively. Median MN values increased significantly 2 hours after procedure. when compared to baseline (pre= 6 vs post= 9 p=0.02). The median of DAP values was 20 Gy cm² (range of 1-277 Gy cm²).

Conclusion: CHD children are exposed to a significant cumulative dose. Both indirect cancer risk estimations and direct DNA data emphasize the need for strict radiation dose optimization in children.

Objective: The serum concentration of amino-terminal procollagen type III (PIIIP) is considered a useful marker of tissue fibrogenesis. The present study tested the hypothesis that: 1) serum PIIIP levels are elevated in patients with congenital heart disease (CHD) and abnormal hemodynamic loading and/or hypoxemia, 2) PIIIP levels are associated with severity of hemodynamic load or hypoxemia, both of which enhance myocardial fibrosis.

Methods and results: Serum PIIIP levels were measured in 5 groups of CHD patients [42 patients with ventricular septal defect (VSD), 26 with coarctation of the aorta (COA, n=19) or aortic stenosis (AS, n=7), 36 with atrial septal defect (ASD), 39 with pulmonary stenosis (PS) and 20 with tetralogy of Fallot (TOF)]. PIIIP levels of CHD patients were significantly higher than those of 42 control subjects (p<0.05, each). Serum PIIIP levels increased in parallel with increased ventricular volume load in VSD and ASD, and with severity of PS. In TOF patients, PIIIP levels correlated negatively with arterial oxygen saturation. Treatment with angiotensin converting enzyme inhibitor (ACEI) was associated with low levels of PIIIP in COA/AS patients despite existing hemodynamic load.

Conclusion: The increased serum PIIIP levels in proportion with the severity of ventricular load or cyanosis suggest enhanced myocardial synthesis of collagen type III in patients with CHD. Suppression of PIIIP level by ACEI suggests the involvement of the renin-angiotensin-aldosterone system in myocardial fibrosis. These data provide the basis for the development of new diagnostic and therapeutic strategies in patients with CHD.

Excessive body weight is known to cluster with cardiovascular (CV) risk factors, but it is not clear which anthropometric obesity measure provides best independent predictive value of coronary artery disease (CAD).

Methods and results: We explored associations between CAD and 4 different obesity measures (body mass index [BMI], waist circumference, waist/height and waist/height²) in a cohort of 16,657 subjects (40.4% men; 20.8% CAD patients), recruited by 700 primary care physicians in 444 Polish cities. 42.8% of subjects were classified as overweight, 31.7% as obese and 39.8% had abdominal obesity. In univariate analyses all obesity measures correlated with CAD (p>0.001), but waist/height² was the strongest discriminator between CAD patients and controls. Age- and sex-adjusted analyses confirmed a graded increase in CAD risk across distributions of all 4 obesity measures - one standard deviation increase in BMI, waist, waist/height and waist/height² increased the odds of CAD by 1.23, 1.24, 1.26 1.27, respectively (all p<0.001). In models fully adjusted for CV risk factors, waist/height² remained the strongest obesity correlate of CAD, being the only independent associate of CAD in men. In a fully adjusted BMI – waist circumference stratified model, sarcopenic obesity (waist > median, BMI < median) and simple obesity (waist and BMI > median) were the strongest independent associates of CAD in men (p=0.008) and women (p>0.001), respectively.

Conclusion: This cross-sectional study showed that waist/height²; may potentially offer a slightly higher predictive value of CAD than BMI or waist circumference and revealed an apparent sexual dimorphism in correlations between obesity measures and CAD .

Background: Adiponectin is an adipose-derived plasma protein that exhibits beneficial actions on the heart. Recently, it was shown that adiponectin levels were elevated in systolic heart failure patients.

Objective: We investigated the association between adiponectin levels and left ventricular (LV) diastolic function in patients with hypertrophic cardiomyopathy (HCM), characterized by diastolic dysfunction.

Methods: Twenty-six patients with HCM showing LV ejection fraction of >60 % were enrolled. We measured LV pressure half-time (T_1/2) as an index of myocardial relaxation. Patients were divided into 2 groups on the basis of baseline T_1/2 (group A: T_1/2< 35 ms, group B: T_1/2≥ 35 ms). Blood samples were simultaneously collected from the coronary sinus (CS) and aortic root (Ao) as well as the peripheral vein (PV) for measurement of plasma adiponectin levels.

Results: Plasma adiponectin levels were significantly higher in group B than in group A. Adiponectin levels in PV were positively correlated with the baseline T_1/2 in patients with HCM. The transcardiac gradient of adiponectin as calculated by the Ao-CS difference was significantly higher in group A than in group B. The transcardiac gradient of adiponectin also inversely correlated with the baseline T_1/2 and adiponectin levels in PV in HCM patients. The expression of AdipR1 but not AdipoR2 in the heart decreased in group B. The baseline T_1/2 was negatively associated with AdipoR1 expression in patients with HCM. Conclusions: These data document that adiponectin is an indicator of LV diastolic dysfunction in patients with HCM.

Myocarditis is a serious and potentially life-threatening disorder that may lead to acute and/or chronic dilated cardiomyopathy and heart failure. Viruses are the most common pathogens associated with myocarditis and may cause cardiac injury by direct damage or through the immune and autoimmune reaction that follows viral infection. Antivirals including pleconaril and interferon beta have been used to treat acute and chronic viral myocarditis in small case series. Most therapeutic strategies that have targeted post-viral and autoimmune inflammation have sought to inhibit adaptive immune components including anti-heart antibodies and T lymphocytes in the setting of lymphocytic or giant cell myocarditis.

Insertion of Left ventricular assist device (LVAD)s (artificial hearts that assist the circulation) in patients with advanced heart failure with deteriorating clinical status is life-saving and they are being inserted into an increasing number of patients with advanced heart failure. LVAD technology is evolving very quickly. LVADs were initially inserted as a bridge to transplantation in patients with advanced heart failure with deteriorating clinical status unable to wait any longer for heart transplantation and the decrease in donors means that an increasing number of patients are requiring LVAD support for survival when their clinical status deteriorates. There is also now compelling evidence that with LVAD unloading recovery of the patients myocardial function can also occur, particularly when combined with pharmacologic therapy, allowing device removal avoiding the need for transplantation, immunosuppression and its associated complications and leaving the patient with an excellent quality of life. This indication, known as "bridge to recovery" is a newer and expanding indication. The future use of LVADs, particularly as survival continues to increase, is extending to their wider use as destination therapy, when the device is inserted lifelong as an alternative to transplantation and this role is likely to increase more in the future.

Objectives: We studied healthy UK Indian Asian and European white subjects to assess whether functional, structural and geometrical properties of the left heart are intrinsically related to ethnicity.

Background: Quantitative assessment of cardiac function and structure is necessary to diagnose heart failure syndromes and is validated to refine risk prediction. A better understanding of the demographic factors that influence these variables is required.

Methods: 453 healthy subjects were recruited from the London Life Sciences Prospective Population (LOLIPOP) study. They underwent 2-D and tissue Doppler echocardiography for quantification of left ventricular (LV) function, LV volumes, left atrial volume index (LAVI), left ventricular mass index (LVMI) and relative wall thickness (RWT).

Results: Indian Asians had attenuated mitral annular systolic velocity (8.9 cm/s vs. 9.5 cm/s, p<0.001), lower mitral annular early diastolic velocity (10.3 cm/s vs. 11.0 cm/s, p<0.001) and higher E/Ea ratio (7.9 vs. 7.0, p<0.001) compared to European whites. Although Indian Asians had significantly smaller left heart volumes and LVMI, they had a significantly higher RWT (0.37 vs. 0.35, p<0.001). After adjustment for covariates, these ethnicity-related differences remained highly significant (p<0.001).

Conclusion: Compared to European whites, Indian Asians have attenuated longitudinal LV function, higher LV filling pressure and demonstrate a greater degree of concentric remodeling independent of other demographic and clinical parameters.

Metformin is a biguanide, insulin-sensitizer that reduces blood sugar levels. There are concerns about the risk of lactic acidosis in patients on metformin having procedures requiring iodinated contrast, and in those with renal impairment or heart failure. The data on which these concerns are based are reviewed, with the conclusion that metformin therapy is rarely to blame for lactic acidosis. A generic policy of stopping metformin 48 h pre and post-procedure in all patients is counter-intuitive, lacks any evidence base and does not conform to the principles of best practice. In patients with heart failure, although the underlying condition can predispose to LA, existing evidence in fact suggests that metformin use is associated with improved outcome rather than elevated risk

Objective: Waist-to-height ratio is an anthropometric indicator of abdominal obesity that accounts for stature. Earlier studies have reported marked associations between the waist-to-height ratio and cardiovascular risk factors. The goal of this study was to compare the associations of waist-to-height ratio, waist girth or waist-to-hip ratio and coronary events incidence.

Design: Prospective study with 10,602 men, aged 50 to 59 years old, recruited between 1991 and 1993 in 3 centres in France and 1 centre in Northern Ireland. Clinical and biological data were obtained at interview by trained staff. During the 10 years of follow-up 659 incident coronary events (CHD) were recorded. The relationships between anthropometric markers and coronary events were estimated by Cox proportional hazards models.

Results: Waist circumference, waist-to-hip ratio and waist-to-height ratios were positively associated with blood pressure (p<0.0001), diabetes (p<0.0001), LDL-cholesterol (p<0.0001), triglycerides (p<0.0001) and inversely correlated to HDL-cholesterol (p<0.0001). There was a linear association between waist circumference, waist-to-hip ratio and waist-to-height ratio and CHD events. The age and centre-adjusted relative risk [95% CI] for CHD were 1.57 [1.22-2.01], 1.75 [1.34-2.87], 2.3 [1.79-2.99] and 1.99 [1.54-2.56] in the 5th quintile vs. the first quintile of waist circumference, waist-to-hip ratio, waist-to-height ratio and BMI distribution, respectively. After further adjustment for school duration, physical activity, tobacco and alcohol consumption, hypertension, diabetes, HDL-cholesterol and triglycerides, the relative risks for CHD were 0.99 [0.76-1.30] for waist circumference (p=0.5), 1.22[0.93-1.60] for waist-to-hip ratio (p=0.1), 1.53[1.16-2.01] for waist-to-height ratio (p=0.03) and 1.30 [0.99-1.71] for BMI (p=0.06).

Conclusion: In middle-aged European men, waist-to-height ratio identifies coronary risk more strongly than waist circumference, waist-to-hip ratio or BMI, though the difference is marginal.

Aims: We investigated the additive prognostic value of the 6MWT to Euroscore in patients with severe aortic stenosis undergoing aortic valve replacement (AVR).

Methods and results: 208 patients with severe AS underwent six minute walk test (6MWT) prior to aortic valve replacement (AVR), as part of a randomized trial (ASSERT) comparing stented and stentless aortic valves.

Clinical follow-up was available for 200 patients up to 12 months. The rate of death, myocardial infarction (MI) or stroke (time to first event) was 13% (n=14) in patients walking <300 m compared to 4% (n=4) in those who walked ≥300 m (p= 0.017). When rate of death, MI or stroke by Euroscore risk was stratified by 6 minute walking distance, the 6MWT added prognostic information. In a Cox regression analysis 6MWT distance was the only variable retained as an independent predictor of the composite outcome of death, MI or stroke at 12 months (HR 0.28 95% CI 0.09-0.85, p=0.025).

Conclusions: The 6MWT is safe and feasible to carry out in patients with severe aortic stenosis prior to AVR, and provides potentially important functional and prognostic information to clinical assessment and the Euroscore risk score.

Objective: To assess autograft, homograft and ventricular function, as well as exercise capacity, in adult patients who have undergone the Ross procedure.

Setting: Single centre paediatric and adult congenital heart disease unit.

Patients: 45 subjects (24.6y, range 16.9-52.2y) who underwent the Ross procedure between 1994 and 2006 (8.1y post Ross operation, range 2.0-14.0y).

Interventions: Cardiovascular magnetic resonance imaging, echocardiography and cardiopulmonary exercise testing.

Main outcome measures: Autograft and homograft stenosis, and regurgitation. Autograft size. Bi-ventricular function, scar volume and exercise capacity.

Results: Mean autograft regurgitation was 6.8±8.3% (trivial regurgitation) and diameter was 40.0±7.0mm. Mean homograft velocity was 2.4±0.6m/s (mild-moderate stenosis) and regurgitation was 6.1±8.3% (trivial regurgitation). Biventricular systolic function was normal (LV EF 63.1± 6.4% and RV EF 60.1± 7.6%). In 38% of cases there was evidence of LV scar, mostly noted within the inter-ventricular septum. The mean exercise capacity achieved was 87± 22% of predicted. There was no correlation between exercise capacity and ventricular function or scar.

Conclusion: This study demonstrates minor autograft and homograft dysfunction in the majority of patients post Ross procedure, associated with good ventricular function and exercise capacity. In addition, minor scar was present in a third of patients with no functional consequences.

Objective: To determine if the Niigata-Chuetsu earthquake of October 2004 increased long-term mortality from acute myocardial infarction (AMI).

Design: A comparative study of mortality rates before and after the earthquake, as well as between the disaster and control areas, by analyzing death certificate data from October 1, 1999 to September 30, 2007.

Setting: The disaster area and a control area in Niigata Prefecture (n=2,448,025 in October 1, 2004) in Japan.

Population: The total population of Niigata Prefecture observed for five years (12,333,429 person-years) before and three years (7,279,076 person-years) after the earthquake.

Main outcome measures: Mortality from AMI (ICD-10, I21 and I22).

Results: Overall mortality rates from AMI five years before and three years after the earthquake in the disaster area were 47.3 and 53.9 per 100,000 person-years, respectively. Change (+6.6 or +14.0%) was significantly different (P=0.0008), compared to the control area, where mortality rates were 42.5 and 42.6 per 100,000 person-years, respectively, and was not significantly different (P=0.9028). In men, a change in AMI mortality before and after the earthquake in the disaster area was +7.1 per 100,000 person-years (+13.4%, P=0.0172), and +2.0 (+4.2%, P=0.2362) in the control area. In women, a change in AMI mortality in the disaster area was +6.2 per 100,000 person-years (+14.9%, P=0.0184) and -1.6 (-4.2%, P=0.2735) in the control area.

Conclusions: The Niigata-Chuetsu earthquake significantly increased long-term mortality from AMI in both men and women. Clinicians and policymakers in public health must recognize the need for long-term prevention of AMI in earthquake disaster areas.

Objectives: To estimate the long-term true change variation ("signal") and short-term within-person variation ("noise") of the different lipids measures and evaluate the best measure and the optimal interval for lipid re-screening.

Design: Retrospective cohort study from 2005 to 2008.

Setting: Centre for Preventive Medicine at a teaching hospital in Tokyo, Japan.

Participants: 15810 adults not taking cholesterol-lowering medications at baseline.

Main outcome measures: Annual measurement of the serum total cholesterol (TC), low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and calculated the ratio of TC/HDL and LDL/HDL. We estimated the ratio of long-term drift ("signal") to the short-term within-person variation ("noise") for each measure.

Results: At baseline, participants (53% male) with a mean age of 49 years old (range: 21 to 92) and a mean TC level of 5.3 mmol/L (SD, 0.9 mmol/L) had annual check-ups over 4 years. Short-term within-person variations of TC, LDL, HDL, TC/HDL, and LDL/HDL were 0.12 (coefficient of variation (CV), 6.4%), 0.08 (CV: 9.4%), 0.02 (CV: 8.0%), 0.08 (CV: 7.9%) and 0.05(CV: 10.6%) mmol²/L² respectively. The ratio of signal to noise at 3 years was largest for TC/HDL (1.6), followed by LDL/HDL (1.5), LDL (0.99), TC (0.8), and HDL (0.7), suggesting cholesterol ratios are more sensitive re-screening measures.

Conclusion: The signal-to-noise ratios of standard single lipid measures (TC, LDL, and HDL) are weak over 3 years and decisions based on these measures are potentially misleading. The ratio, TC/HDL and LDL/HDL, appears to be better measure for monitoring assessments. The lipid re-screening interval should be more than 3 years for those not taking cholesterol-lowering drugs.

Objective: To estimate the cost-effectiveness of primary angioplasty compared to thrombolysis for acute ST-elevation myocardial infarction.

Design: Cost analysis of UK observational database, incorporated into decision analytic model.

Methods: We compared patients receiving treatment within a comprehensive angioplasty service to control patients receiving thrombolysis-based care. The treatment costs and delays to treatment of thrombolysis and angioplasty were estimated. These estimates were then incorporated into an existing model of cost effectiveness that synthesises evidence from 22 randomised trials to estimate health outcomes in terms of quality-adjusted life years (QALYs).

Main outcome measures: Costs from a health service perspective and outcomes measured as quality-adjusted.

Results: The mean cost of the initial treatment episode was £3,509 for thrombolysis at control sites, £5,176 for angioplasty in usual working hours at NIAP sites and an additional £245 if undertaken out of hours . Angioplasty-based care had an incremental cost of £4520 per QALY gained and 0.9 probability of being cost-effective at a threshold of £20,000 per QALY gained. This probability was >0.95 if patients were directly admitted to the cardiac catheter laboratory, 0.75 if admitted via the emergency department or coronary care unit, and 0.38 if transferred to the angioplasty centre from another hospital.

Conclusions: Overall, primary angioplasty based care is highly likely to be cost-effective at an assumed threshold of £20,000 per QALY gained. It is more likely to be cost-effective if patients are admitted directly to the cardiac catheter laboratory than via other hospital departments, or if transferred from another hospital.

Objective: To identify the key predictors of performance on a six-minute walk and health related quality of life (QOL) one year after cardiac valve replacement and to use the predictors to guide clinical practice and optimise outcome.

Design: Prospective cohort study.

Setting: Tertiary cardiothoracic centre in the UK.

Patients: 225 patients having first time valve replacement with a mean age 67.1 (12.1) years.

Main outcome measures: Mortality, morbidity, NYHA, performance on a six-minute walk and health related QOL one year after surgery.

Results: One year after valve replacement 90% of patients were alive and free from a major event related to their surgery. NYHA category fell by 0.6. Performance on a six-minute walk improved by 42% and QOL improved on all subscales and both composite scores of the SF-36 QOL questionnaire. Although physical QOL scores improved they did not normalise, unlike the mental QOL scores which were near normal on both occasions. Independent baseline predictors of six-minute walk performance at one year were baseline walk performance, age and belief in surgery as a treatment. Independent baseline predictors of one year physical QOL were baseline physical QOL and walk performance. Independent baseline predictors one year mental QOL were depression, baseline mental QOL and age, with age having a positive effect.

Conclusions: One year after valve replacement patients can expect a significant improvement in their exercise tolerance and QOL but their physical QOL is unlikely to be normal. Outcome may be improved by treating depression and modifying negative illness beliefs preoperatively.

Objectives: Endothelial progenitor cells (EPCs) are circulating mononuclear cells with the capacity to mature into endothelial cells and contribute to vascular repair. We assessed the effect of local vascular injury during percutaneous coronary intervention (PCI) on circulating EPCs in patients with coronary artery disease.

Design and setting: Prospective case-control study in a University teaching hospital.

Patients: Fifty-four patients undergoing elective coronary angiography.

Interventions and main outcome measures: EPCs were quantified by flow cytometry (CD34⁺KDR⁺ phenotype) complemented by real-time PCR, and the colony forming unit (CFU-EC) functional assay, before and during the first 24 hours after diagnostic angiography (n=27) or PCI (n=27).

Results: Coronary intervention, but not diagnostic angiography, resulted in an increase in blood neutrophil count (P<0.001) and C-reactive protein concentrations (P=0.001) in the absence of significant myocardial necrosis. Twenty-four hours after PCI, CFU-ECs increased 3-fold (median [IQR], 4.4 [1.3-13.8] vs 16.0 [2.1-35.0], P=0.01), although circulating CD34⁺KDR⁺ cells (0.019±0.004 vs 0.016±0.003 % of leucocytes, P=0.62) and leucocyte CD34 mRNA (relative quantity 2.3±0.5 vs 2.1±0.4, P=0.21) did not. There was no correlation between CFU-ECs and CD34+KDR+ cells.

Conclusions: Local vascular injury following PCI results in a systemic inflammatory response and increases functional CFU-ECs. This increase was not associated with an early mobilisation of CD34⁺KDR⁺ cells, suggesting these cells are not the primary source of EPCs involved in the immediate response to vascular injury.

Objective: To examine the mid and long term outcomes in patients with obstructive hypertrophic cardiomyopathy (HCM) submitted to pacing.

Design: Prospective, observational study.

Setting: Single, non-referral centre.

Patients and intervention: Fifty patients (62±11years) with HCM refractory to medical therapy, all in NYHA class III or IV, and with a rest gradient >50mmHg underwent a dual-chamber pacemaker implantation. Patients were followed-up up to 10 years (mean 5.0±2.9, range 0.6-10.1).

Results: During the first year of follow-up, rest gradients decreased (baseline 86±29mmHg; 3-months 55±37; l-year 41±26; p=0.0001). NYHA class improved (p<0.0001), as well as exercise tolerance (p<0.0001). The physical and mental components of the quality of life instrument SF-36 improved as well (p=0.0001). Left ventricular wall thickness remained unchanged, while ejection fraction decreased (p=0.002). During the long-term follow-up, an additional reduction in obstruction was found (final rest gradient 28±24mmHg, p<0.02). Those patients that did not improved to NYHA class I or II and remained with obstruction were submitted to other therapies (6 to alcohol ablation, 3 to surgical myectomy).

Conclusions: Pacing in HCM results in a significant reduction in obstruction, improvement of symptoms and exercise capacity that is progressive and may be achieved after a long period of time. In our series, only 18% of cases needed a more aggressive therapy to relieve residual obstruction and obtain a satisfactory symptomatic status. In conclusion, these results emphasize the necessity of new controlled studies of pacing with a longer follow-up.

Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) are important biomarkers in the diagnosis and risk stratification for heart failure (HF). These peptides are synthesized as inactive precursors, pro-ANP and pro-BNP, which are converted to biologically active 28-amino-acid ANP and 32-amino-acid BNP, respectively. Most immunoassays currently used in the clinical setting, however, do not determine precise molecular forms of these natriuretic peptides, which may vary depending on the pathophysiological state of HF. Analysis from chromatography-based studies reveals that in HF, inactive pro-ANP and pro-BNP forms often predominate. This indicates that the bioactive forms of natriuretic peptides may not be processed proportionally in patients with advanced HF. Distinguishing the bioactive natriuretic peptides from their inactive forms in plasma may help to define the role of these peptides in the pathogenesis of HF and provide new insights into the treatment of the disease.

Focal atrial tachycardia is a relative uncommon arrhythmia. Nevertheless, the generally poor response to medical therapy in focal atrial tachycardia can pose several problems in the managements of highly symptomatic patients. Moreover, atrial tachycardia can trigger other atrial arrhythmias like atrial fibrillation and flutter. Radiofrequency ablation of focal atrial tachycardia is extremely successful and this approach is becoming the treatment of choice for symptomatic patients.

In this review, we describe the pathophysiology, anatomic localisation, clinical features, diagnosis and therapeutic options for the management of focal atrial tachycardia.

Worsening renal function during treatment of acute decompensated heart failure (ADHF) often complicates the treatment course of heart failure. Furthermore, the development of worsening renal function is a strong independent predictor of long-term adverse outcomes. Sometimes referred to as "cardio-renal syndrome," the definition varies widely, and the overall understanding of pathogenesis is limited. This is likely due to the lack of precision and characterization of renal compromise during treatment of heart failure. Traditionally, impairment of cardiac output and relative under-filling of arterial perfusion has been attributed to the predominant cause. Emerging data has led to a resurgence of interest in the importance of venous congestion and elevated intra-abdominal pressure rather than confining to impaired forward cardiac output as the primary driver of renal impairment. These revived concepts may support the role of novel renal-sparing approaches to salt and water removal and renal preservation, but better ways to distinguish hemodynamic versus other nephrotoxic etiologies are needed.

Mitral regurgitation is a frequent finding in patients with aortic stenosis scheduled for aortic valve replacement. Detection of mitral regurgitation in such patients has important implications, as it can independently affect functional status and prognosis. When mitral regurgitation is moderate-to-severe, a decision to operate on both valves should only be made following a careful clinical and echocardiographic assessment. Indeed, double-valve surgery increases peri- and post-operative risks, and mitral regurgitation may improve spontaneously after isolated aortic valve replacement. Better understanding of the determinants of these changes appears particularly crucial in the light of recent advances in percutaneous aortic valve replacement.

Objective: To describe the cardiac anomalies and outcome in the fetus with left atrial isomerism.

Methods: All fetuses with a diagnosis of left atrial isomerism between 1998-2008 were identified. Gestational age at diagnosis, the nuchal translucency, the karyotype, the cardiac findings and outcome were noted. A literature search from 1990 identified 4 publications reporting 10 or more cases of fetal left atrial isomerism. The same data, where available, was collected from these papers for comparison.

Results: There were 41 fetuses with this diagnosis seen in our centre. All cases had an interrupted inferior vena cava with azygous continuation. Associated cardiac defects were similar in our series and in the 129 cases reported in the literature and are therefore grouped together. They included complete atrioventricular septal defect (68%), complete heart block (38%), viscerocardiac heterotaxy (54%), double outlet right ventricle (23%), right ventricular outflow tract obstruction (35%) left ventricular outflow tract obstruction (21%) and total anomalous pulmonary vein drainage (5%). In our series, there were 22 pregnancy terminations, 7 intrauterine deaths, one neonatal death, one infant death, and one was lost to follow-up. Of the continuing pregnancies only 50% in our series and 58% in the reported series survived.

Conclusion: Left atrial isomerism presents a varied spectrum of cardiac malformations when it is detected prenatally. Complete heart block, complex cardiac abnormalities and fetal hydrops are poor prognostic features. Those with only minor cardiac malformations are at risk postnatally for biliary atresia and for bowel obstruction due to malrotation.

Objective and design: PCI of left main coronary artery (LMCA) disease in the bare stent era was limited by high restenosis rates which eventually manifested by sudden death in unprotected cases. Clinical and angiographic restenosis has been substantially reduced by drug-eluting stents reviving therefore this indication for PCI inspite of absence of direct comparative studies with CABG surgery. We assessed the acute, mid- and long-term outcomes of sirolimus-eluting stent treated patients for unprotected LMCA stenoses and compared them with those treated for protected LMCA disease in the same time period from the German Cypher Registry.

Setting and patients: The German Cypher Registry included 6755 patients. Eighty-two patients treated for unprotected LMCA disease were compared with 118 patients treated for protected LMCA stenoses. All patients were treated by sirolimus-eluting stents. The primary end point was death, myocardial infarction and target vessel revascularization at six months follow-up. Survival free of myocardial infarction at long-term was considered as safety endpoint.

Results: One third of the patients in both groups were treated for the distal left main bifurcation. Angiographic success was 98.5% for both groups. The cumulative combined incidence of all cause death, non-fatal myocardial infarction and TVR at 6 months was 14.1% in the unprotected LMCA group and 13.1% in the protected group (HR = 0.81 [95% CI 0.37 - 1.74] p= 0.8). At long-term death/myocardial infarction were reported among 20.2% (95% CI 13.5% - 29.6%) of the protected group versus 11.8% (95% CI 6.3% - 21.4%) of the unprotected group (p= 0.2).

Conclusion: Sirolimus-eluting stent treatment of unprotected and protected LMCA stenoses is technically feasible in the widespread routine clinical use. Acceptable long-term clinical results can be achieved, with no particular safety concerns regarding unprotected LMCA disease treatment.