We obtained results from all randomized trials evaluating the benefits of adjunctive Gp IIb-IIIa inhibitors among STEMI patients undergoing primary angioplasty. The literature was scanned by formal searches of electronic databases (MEDLINE and CENTRAL) from January 1990 to September 2008. The following key words were used: randomized trial, myocardial infarction, reperfusion, primary angioplasty, Gp IIb-IIIa inhibitors, abciximab, tirofiban, and eptifibatide. Clinical endpoint was mortality at 30 days. Major bleeding complications were assessed as safety endpoint. No language restriction was applied. A total of 16 randomized trials were finally included in the meta-analysis, involving 10 085 patients (5094 or 50.5% in the Gp IIb-IIIa inhibitors group and 4991 or 49.5% in the control group. Gp IIb-IIIa inhibitors did not reduce 30 day mortality (2.8 vs. 2.9%, P = 0.75) or re-infarction (1.5 vs. 1.9%, P = 0.22), but were associated with higher risk of major bleeding complications (4.1 vs. 2.7%, P = 0.0004). However, we observed a significant relationship between patient's risk profile and benefits from adjunctive Gp IIb-IIIa inhibitors in terms of death (P = 0.008) but not re-infarction (P = 0.25).

This meta-analysis shows a significant relationship between benefits in mortality from Gp IIb-IIIa inhibitors and patient's risk profile. Thus, Gp IIb-IIIa inhibitors should be strongly considered among high-risk patients.

This prospective observational cohort study included 6816 consecutive patients that underwent successful DES implantation. Primary endpoint was definite stent thrombosis (ST). During 4 years of follow-up, definite ST was observed in 73 patients, corresponding to a cumulative incidence of 1.2%. Cumulative incidence of ST at 30 days was 0.5 and 0.8% at 1 year, respectively. Discontinuation of clopidogrel therapy was significantly associated with ST only in the first 6 months after the procedure (P < 0.001). During that period, the median time interval from clopidogrel discontinuation to ST was 9 days [interquartile range (IQR) 5.5–22.5] while thereafter it was 104.3 days (IQR 7.4–294.8).

The 4 year incidence of ST after DES implantation is low. A relevant number of ST occur early after discontinuation of clopidogrel therapy. The dependence of ST on discontinuation of clopidogrel therapy seems to be mostly confined to the first 6 months after DES implantation. However, specifically designed randomized studies are required to establish the optimal length of clopidogrel therapy after DES implantation.

Female adult Göttingen swine (n = 15) underwent left anterior descending coronary artery balloon occlusion to create reproducible ischaemia–reperfusion infarctions. Bone-marrow-derived MSCs were isolated and expanded from each animal. Twelve weeks post-myocardial infarction (MI), animals were randomized to receive surgical injection of either phosphate buffered saline (placebo, n = 6), 20 million (low dose, n = 3), or 200 million (high dose, n = 6) autologous MSCs in the infarct and border zone. Injections were administered to the beating heart via left anterior thoracotomy. Serial cardiac magnetic resonance imaging was performed to evaluate infarct size, myocardial blood flow (MBF), and left ventricular (LV) function. There was no difference in mortality, post-injection arrhythmias, cardiac enzyme release, or systemic inflammatory markers between groups. Whereas MI size remained constant in placebo and exhibited a trend towards reduction in low dose, high-dose MSC therapy reduced infarct size from 18.2 ± 0.9 to 14.4 ± 1.0% (P = 0.02) of LV mass. In addition, both low and high-dose treatments increased regional contractility and MBF in both infarct and border zones. Ectopic tissue formation was not observed with MSCs.

Together these data demonstrate that autologous MSCs can be safely delivered in an adult heart failure model, producing substantial structural and functional reverse remodelling. These findings demonstrate the safety and efficacy of autologous MSC therapy and support clinical trials of MSC therapy in patients with chronic ischaemic cardiomyopathy.

Patients hospitalized with ischaemic symptoms and evidence of NSTEACS were randomized to early (at hospitalization) or late (at hospital discharge) treatment with irbesartan 150 mg/day followed by 300 mg/day on day 15 (n = 212) or enalapril 10 mg/day followed by 20 mg/day on day 15 (n = 217) to day 60. The primary endpoint was the change from baseline in high-sensitivity C-reactive protein (hs-C-reactive protein) at day 60; secondary endpoints included changes in troponin I, B-type natriuretic peptide, microalbuminuria, interleukin 6, myeloperoxidase, secretory non-pancreatic type II phospholipase A2, ischaemia-modified albumin, soluble CD40 ligand, matrix metalloproteinase-9, aldosterone, and blood pressure. High-sensitivity C-reactive protein levels were comparable in both the irbesartan and enalapril treatment arms. There were no treatment-related differences in any of the biomarkers measured. Changes in inflammatory markers were unaffected by the timing of treatment initiation. Both treatments were well tolerated, with no differences in major adverse cardiac events.

In patients with NSTEACS, inflammatory markers decreased over time in both treatment arms, with no differences between irbesartan and enalapril.

Plasma concentrations of sPLA₂ (ELISA) and sPLA₂ activity (selective fluorometric assay) were measured at baseline in a cohort of 1024 patients aged 30–70 years with CHD. The Cox-proportional hazards model was used to determine the prognostic value of sPLA₂ on a combined cardiovascular disease (CVD) endpoint after adjustment for covariates. During a mean follow-up of 4.1 years, 93 patients (9.1%) experienced a secondary CVD event. In a multivariable model, sPLA₂ mass and activity were associated with hazard ratios of secondary CVD events of 2.07 (95% CI, 1.17–3.66) and 1.65 (95% CI 0.96–2.84) for mass and activity, respectively, when extreme tertiles were compared. Further adjustment for cystatin C, N-terminal-probrain natriuretic peptide, C-reactive protein, and lipoprotein-associated phospholipase A₂ attenuated the associations, still showing a positive trend for mass but a less clear pattern for activity. However, when sPLA₂ mass and activity were analysed as continuous variables both still showed a statistically significant increase in risk in all models.

Secretory phospholipase A₂ mass and activity appear to be predictive of secondary CVD events in patients with CHD.

Growth differentiation factor-15 was measured before and 360 days (median) after implantation in 158 patients with heart failure [age 68 ± 11 years (mean ± SD), left ventricular ejection fraction (LVEF) 23.1 ± 9.8%, New York Class Association (NYHA) class III (n = 117) or IV (n = 41), and QRS 153.9 ± 28.2 ms] undergoing CRT and followed up for a maximum of 5.4 years for events. In a stepwise Cox proportional hazards model with bootstrapping, adopting log GDF-15, log NT pro-BNP, LVEF, and NYHA class as independent variables, only log GDF-15 [hazard ratio (HR), 3.76; P = 0.0049] and log NT pro-BNP (HR, 2.12; P = 0.0171) remained in the final model. In the latter, the bias-corrected slope was 0.85, the optimism (O) was –0.06, and the c-statistic was 0.74, indicating excellent internal validity. In univariate analyses, log GDF-15 [HR, 5.31; 95% confidence interval (CI), 2.31–11.9; likelihood ratio (LR) ² = 14.6; P < 0.0001], NT pro-BNP (HR, 2.79; 95% CI, 1.55–5.26; LR ² = 10.4; P = 0.0004), and the combination of both biomarkers (HR, 7.03; 95% CI, 2.91–17.5; LR ² = 19.1; P < 0.0001) emerged as significant predictors. The biomarker combination was associated with the highest LR ² for all endpoints.

Pre-implant GDF-15 is a strong predictor of mortality and morbidity after CRT, independent of NT pro-BNP. The predictive value of these analytes is enhanced by combined measurement.

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

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

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

Analyses were performed on 5532 patients with ST-elevation myocardial infarction from the Assessment of Pexelizumab in Acute Myocardial Infarction trial. The primary objective of this analysis was to ascertain the relation between red blood cell transfusion and 90-day mortality in patients with recent myocardial infarction. We initially determined the baseline and in-hospital predictors of transfusion (multivariable logistic regressions) and subsequently assessed the association between transfusion and mortality using a series of Cox proportional hazards regression combined to a landmark analyses. A total of 213 patients (3.9%) received a transfusion. Transfusion remained significantly associated with mortality [hazards ratio = 2.16 (1.20–3.88)], despite adjustment for baseline characteristics, in-hospital co-interventions, and for propensity of receiving a transfusion. Among patients who survived to hospital discharge, however, the hazard of death was not different in patients treated with transfusion.

Transfusion is associated with 90-day mortality in acute myocardial infarction treated with primary percutaneous coronary intervention. Although transfusion may be causally related to mortality, it is likely that at least part of the association is due to confounding. This association illustrates the complex relationship between transfusion, bleeding, and mortality and underscores the need for further research to understand the relationship between transfusion and clinical outcomes.

Patients with CAD were identified in the Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease (APPROACH) registry between January 2001 and March 2006. Analyses were conducted separately by treatment strategy [medical management only, percutaneous coronary intervention (PCI), or coronary artery bypass grafting (CABG)]. Patients were grouped according to six BMI categories. Multivariable-adjusted hazard ratios (HRs) for mortality were calculated using the Cox regression with the referent group for all analyses being normal BMI (18.5–24.9 kg/m²). The cohort included 31 021 patients with a median follow-up time of 46 months. In the medically managed only group, BMIs of 25.0–29.9 and 30.0–34.9 kg/m² were associated with significantly lower mortality compared with normal BMI patients (adjusted HR 0.72; 95% CI 0.63–0.83 and adjusted HR 0.82; 95% CI 0.69.0–0.98, respectively). In the CABG group, BMI of 30.0–34.9 kg/m² had the lowest risk of mortality (adjusted HR 0.75; 95% CI 0.61–0.94), whereas in the PCI group, BMI of 35.0–39.9 kg/m² had the lowest risk of mortality (adjusted HR 0.65; 95% CI 0.47–0.90). Patients who were overweight or have mild or moderate obesity were also more likely to undergo revascularization procedures compared with those with normal BMI, despite having lower risk coronary anatomy.

A paradoxical association between BMI and survival exists in patients with established CAD irrespective of treatment strategy. Patients with obesity may be presenting earlier and receiving more aggressive treatment compared with those with normal BMI.

Seventy-six HCM mutation carriers from 32 families identified by predictive DNA testing underwent cardiac evaluation including history, examination, electrocardiography, Doppler echocardiography, exercise testing, and 24 h Holter monitoring. The published diagnostic criteria for HCM in adult members of affected families were used to diagnose HCM. Thirty-three (43%) men and 43 (57%) women with a mean age of 42 years (range 16–79) were examined; in 31 (41%) HCM was diagnosed. Disease penetrance was age related and men were more often affected than women (P = 0.04). Myosin Binding Protein C (MYBPC3) mutation carriers were affected at higher age than Myosin Heavy Chain (MYH7) mutation carriers (P = 0.01). Risk factors for SCD were present in affected and unaffected carriers.

Hypertrophic cardiomyopathy was diagnosed in 41% of carriers. Disease penetrance was age dependent, warranting repeated cardiologic evaluation. The MYBPC3 mutation carriers were affected at higher age than MYH7 mutation carriers. Risk factors for SCD were present in carriers with and without HCM. Follow-up studies are necessary to evaluate the effectiveness of risk stratification for SCD in this population.

This was a cohort study, with prospective data collection. We studied 1380 patients, referred to a cardiomyopathy clinic in London, UK [mean age 42 years (SD 15); 62% male; mean follow-up 54 (SD 49) months]. Patients underwent two-dimensional and Doppler echocardiography, upright exercise testing, and Holter monitoring. Twenty-seven patients [mean age 40 (SD 14) years (18–64); 22 (81.5%) male] had NSVT (24) or ventricular fibrillation (VF) (3) during exercise. During exercise, 13 (54.2%) had more than one run of NSVT (maximum 5) with a mean heart rate of 221 (SD 48) b.p.m. Patients with exercise NSVT/VF had more severe hypertrophy (22.6 vs. 19.5 mm, P = 0.009) and larger left atria (47.3 vs. 43.7 mm, P = 0.03). Male gender was significantly associated with exercise NSVT/VF [22 (81.5%) vs. 832 (61.5%), P = 0.03]. Eight (29.6%) of the exercise NSVT/VF patients died or had a cardiac event (SD/ICD discharge/transplant) compared with 150 (11.1%) patients without exercise NSVT/VF, P = 0.008. Patients with NSVT/VF had a 3.73-fold increase in risk of SD/ICD discharge (HR 95% CI: 1.61–8.63, P = 0.002). Exercise NSVT alone was associated with a 2.82-fold increased risk (HR 95% CI: 1.02–7.75, P = 0.049). In multivariable analysis with other risk markers, exercise NSVT/VF (but not NSVT alone) was independently associated with an increased risk of SD/ICD [HR 3.14 (95% CI: 1.29–7.61, P = 0.01)].

Ventricular arrhythmia during symptom limited exercise is rare in patients with hypertrophic cardiomyopathy, but is associated with an increased risk of sudden cardiac death.

The study was designed as a prospective randomized cross-over trial with each physician completing a 24 h (h) OCD and a 24 h control period including a regular 8 h non-OCD. Thirty healthy physicians with a median age of 33.5 years (range 29.0–45.0) were analysed. Twenty-four hours ECG and BP monitoring were performed and participants were instructed to fill out an event diary and perform a 24 h urine collection. Furthermore, blood was drawn before and after OCD and control day. Twenty-four hours ECG showed a higher rate of ventricular premature beats (VPB) during early morning hours (VPB 0–6 h, 0.5 vs. 0.0, P = 0.047) and increased low-frequency normalized units (29.3 vs. 25.5, P = 0.050) during night shift when compared with respective control night at home. During OCD, BP monitoring revealed a greater diastolic BP throughout 24 h (83.5 vs. 80.2 mmHg, P = 0.025) as well as during night-time (75.4 vs. 73.0, P = 0.028) associated with a higher rate of systolic BP more than 125 mmHg during sleep time. Tumour necrosis factor alpha concentrations increased significantly during night shift (0.76 vs. 0.05 pg/mL, P = 0.045). Urinary noradrenaline excretion was greater during OCD when compared with control day (46.0 vs. 36.0 µg/24 h, P = 0.007).

Our results highlight the association of OCD with an increased risk profile for cardiovascular disease. In addition to the acute effects observed, frequent night-calls over a longer period possibly elicit sustained alterations in cardiovascular homeostasis.

A prospective study included patients without previous diagnosis of diabetes that were referred for PCI between November 2005 and May 2006. Major cardiac events were registered after admission and during 12 months of follow-up, and oral glucose tolerance was tested at 15 days after hospital discharge. Six hundred and sixty-two consecutive patients were referred to our hospital for PCI. The distribution of the glycometabolic state of the entire population was (95% CI): known diabetes 28.8% (25.2–32.6), newly detected diabetes 16.2% (13.1–19.8), impaired glucose tolerance 24.5% (20.8–28.5), impaired fasting glucose 1% (0.4–2.4), and normal glucose regulation 29.5% (25.5–33.7). In a multivariable analysis, the presence of newly detected diabetes was not an independent predictor of cardiac events after 1 year of follow-up.

The prevalence of diabetes in patients who underwent PCI was very high (45%), 35% of which was patients with newly detected diabetes. In our series newly detected diabetes was not an independent predictor of outcome at 12 months. Nevertheless, this finding requires independent confirmation in other series to draw general conclusions on the whole spectrum of percutaneous interventions.

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

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

This prospective, randomized, open-label, active-controlled trial was conducted at two tertiary referral cardiology centres in Munich, Germany. Patients presenting with stable coronary disease or acute coronary syndromes undergoing DES implantation in de novo native-vessel coronary lesions were randomly assigned to treatment with biodegradable polymer DES (rapamycin-eluting; n = 1299) or permanent polymer DES (n = 1304: rapamycin-eluting, Cypher, n = 652; or everolimus-eluting, Xience, n = 652) and underwent clinical follow-up to 1 year. The primary endpoint was a composite of cardiac death, myocardial infarction (MI) related to the target vessel, or revascularization related to the target lesion (TLR). Biodegradable polymer DES was non-inferior to permanent polymer DES concerning the primary endpoint [13.8 vs. 14.4%, respectively, P_{non-inferiority} 0.005; relative risk = 0.96 (95% confidence interval, 0.78–1.17), P_superiority = 0.66]. Biodegradable polymer DES in comparison with permanent polymer DES showed similar rates of cardiac death or MI related to the target vessel (6.3 vs. 6.2%, P = 0.94), TLR (8.8 vs. 9.4%, P = 0.58), and stent thrombosis (definite/probable: 1.0 vs. 1.5%, P = 0.29). Subgroup analysis of the biodegradable polymer DES vs. individual Cypher and Xience stent arms revealed no signal of performance difference.

A biodegradable polymer rapamycin-eluting stent is non-inferior to permanent polymer-based DES in terms of clinical efficacy over 1 year. These results provide a framework for testing the potential clinical advantage of biodegradable polymer DES over the medium to long term.

The trial was registered at ClinicalTrials.gov (identifier: NCT00598676).

A total of 140 centres from 13 European countries contributed data from consecutive patients successfully implanted with a CRT device with or without an ICD between November 2008 and June 2009. The total number of patients enrolled was 2438. The median age of the patients was 70 years (IQR 62–76) and 31% were ≥75 years. It was found that 78% were in NYHA functional class III or IV and 22% in I or II. The mean ejection fraction was 27% ± 8 and the mean QRS duration 157 ms ± 32. The QRS duration was <120 ms in 9%. Atrial fibrillation was reported in 23%. It was found that 26% of patients had a previously implanted permanent pacemaker or ICD; 76% of procedures were performed by an electrophysiologist; 82% had an elective admission for implantation and the median duration of hospitalization was 3 days (IQR 2–7); and 73% received a CRT-D device which was more often implanted in men, younger patients, and with ischaemic aetiology. The mean QRS duration was reduced to 133 ms ± 27 (P < 0.0001) at discharge. Peri-procedural complication rates were comparable to the rates reported in randomized trials.

This CRT survey provides important information describing current European practice with regard to patient demographics, selection criteria, procedural routines, and status at discharge. These data should be useful for benchmarking individual patient management and national practice against wider experience.

The KYOTO HEART Study was of a multicentre, Prospective Randomised Open Blinded Endpoint (PROBE) design, and the primary endpoint was a composite of fatal and non-fatal cardiovascular events (clintrials.gov NCT00149227). A total of 3031 Japanese patients (43% female, mean 66 years) with uncontrolled hypertension were randomized to either valsartan add-on or non-ARB treatment. Median follow-up period was 3.27 years. In both groups, blood pressure at baseline was 157/88 and 133/76 mmHg at the end of study. Compared with non-ARB arm, valsartan add-on arm had fewer primary endpoints (83 vs. 155; HR 0.55, 95% CI 0.42–0.72, P = 0.00001).

Valsartan add-on treatment to improve blood pressure control prevented more cardiovascular events than conventional non-ARB treatment in high-risk hypertensive patients in Japan. These benefits cannot be entirely explained by a difference in blood pressure control.

A total of 286 patients were grouped according to relative reduction in left ventricular end-systolic volume (LVESV) after 6 months of CRT: super-responders (reduction in LVESV ≥30%), responders (reduction in LVESV 15–29%), non-responders (reduction in LVESV 0–14%), and negative responders (increase in LVESV). In addition, three subgroups were formed according to clinical and/or echocardiographic response: +/+ responders (clinical improvement and a reduction in LVESV ≥15%), +/– responders (clinical improvement or a reduction in LVESV ≥15%), and –/– responders (no clinical improvement and no reduction in LVESV ≥15%). Differences in clinical and echocardiographic baseline characteristics between these subgroups were analysed. Super-responders were more frequently females, had non-ischaemic heart failure (HF), and had a wider QRS complex and more extensive mechanical dyssynchrony at baseline. Conversely, negative responders were more frequently in New York Heart Association class IV and had a history of ventricular tachycardia (VT). Combined positive responders after CRT (+/+ responders) had more non-ischaemic aetiology, more extensive mechanical dyssynchrony at baseline, and no history of VT.

Sub-analysis of data from PROSPECT showed that gender, aetiology of HF, QRS duration, severity of HF, a history of VT, and the presence of baseline mechanical dyssynchrony influence clinical and/or LV reverse remodelling after CRT. Although integration of information about these characteristics would improve patient selection and counselling for CRT, further randomized controlled trials are necessary prior to changing the current guidelines regarding patient selection for CRT.

We performed exercise treadmill testing with stress echocardiography in 934 ambulatory subjects with CHD. End-systolic volume was measured immediately before and after exercise using 2D echocardiography. We defined ESV reversal as an increase in ESV after exercise, and we examined the association of ESV reversal with all-cause mortality during a median follow-up of 3.92 years. Of the 934 participants, 199 (21%) had ESV reversal. At the end of follow-up, mortality was higher among participants with ESV reversal than those without (26 vs. 11%; P < 0.001). After adjustment for clinical covariates, ESV reversal remained predictive of all-cause mortality (HR 2.0; 95% CI 1.4–2.9; P = 0.001). The association of ESV reversal with mortality also persisted after adjustment for exercise-induced wall-motion abnormalities (HR 1.7; 95% CI 1.1–2.3, P = 0.006). To determine if the effect of ESV reversal was independent from other echocardiographic measurements, we created a separate model adjusting for resting LV ejection fraction, ESV, end-diastolic volume, and LV mass. End-systolic volume reversal was the only significant predictor of mortality in this model (HR 2.1, 95% CI 1.4–3.0, P < 0.001).

End-systolic volume reversal is a novel parameter that independently predicts mortality in patients with CHD undergoing exercise treadmill echocardiography, even after adjustment for a wide range of clinical, echocardiographic, and treadmill exercise variables. Because measurement of ESV is simple, reproducible, and requires no additional imaging views, identification of ESV reversal during exercise echocardiography can provide useful complementary information for risk stratification.

Patients had extensive cardiological examinations including electrocardiograms, echocardiograms, ventilation–perfusion scans, and cardiac catheterizations. All patients died before the age of 16 months because of severe progressive primary PVS. Chromosomal analysis revealed normal karyotypes. We performed a genome-wide linkage analysis using 250 K single nucleotide polymorphism arrays and found the first locus for primary PVS on chromosome 2q35-2q36.1 [multipoint logarithms (base 10) of odds (LOD) scores 3.6]. By fine-mapping with microsatellite markers, we confirmed the homozygous region that extended 6.6 Mb (D2S164–D2S133). Sequencing 12 (188 exons) of the 88 genes from the region revealed no disease-causing sequence variations.

Our findings open perspectives for the identification of the genetic cause(s) leading to PVS, which might contribute to elucidate the pathological mechanisms involved in this disorder.