RNA Profiling in Human and Murine Transplanted Hearts: Identification and Validation of Therapeutic Targets for Acute Cardiac and Renal Allograft Rejection.

Acute cellular rejection (ACR) is the adverse response of the recipient's immune system against the allogeneic graft. Using human surveillance endomyocardial biopsies (EMBs) manifesting ACR and murine allogeneic grafts, we profiled implicated microRNAs (miRs) and mRNAs. MiR profiling showed that miR-21, -142-3p, -142-5p, -146a, -146b, -155, -222, -223, and -494 increased during ACR in humans and mice, whereas miR-149-5p decreased. mRNA profiling revealed 70 common differentially regulated transcripts, all involved in immune signaling and immune-related diseases. Interestingly, 33 of 70 transcripts function downstream of IL-6 and its transcription factor spleen focus forming virus proviral integration oncogene (SPI1), an established target of miR-155, the most upregulated miR in human EMBs manifesting rejection. In a mouse model of cardiac transplantation, miR-155 absence and pharmacological inhibition attenuated ACR, demonstrating the causal involvement and therapeutic potential of miRs. Finally, we corroborated our miR signature in acute cellular renal allograft rejection, suggesting a nonorgan specific signature of acute rejection. We concluded that miR and mRNA profiling in human and murine ACR revealed the shared significant dysregulation of immune genes. Inflammatory miRs, for example miR-155, and transcripts, in particular those related to the IL-6 pathway, are promising therapeutic targets to prevent acute allograft rejection.

Pre-hospital treatment of STEMI patients. A scientific statement of the Working Group Acute Cardiac Care of the European Society of Cardiology.

In ST-elevation myocardial infarction (STEMI) the pre-hospital phase is the most critical, as the administration of the most appropriate treatment in a timely manner is instrumental for mortality reduction. STEMI systems of care based on networks of medical institutions connected by an efficient emergency medical service are pivotal. The first steps are devoted to minimize the patient's delay in seeking care, rapidly dispatch a properly staffed and equipped ambulance to make the diagnosis on scene, deliver initial drug therapy and transport the patient to the most appropriate (not necessarily the closest) cardiac facility. Primary PCI is the treatment of choice, but thrombolysis followed by coronary angiography and possibly PCI is a valid alternative, according to patient's baseline risk, time from symptoms onset and primary PCI-related delay. Paramedics and nurses have an important role in pre-hospital STEMI care and their empowerment is essential to increase the effectiveness of the system. Strong cooperation between cardiologists and emergency medicine doctors is mandatory for optimal pre-hospital STEMI care. Scientific societies have an important role in guideline implementation as well as in developing quality indicators and performance measures; health care professionals must overcome existing barriers to optimal care together with political and administrative decision makers.

Departures from the protocol during conduct of a clinical trial: a pattern from the data record consistent with a learning curve.

OBJECTIVE: Recognition of learning curves in medical skill acquisition has enhanced patient safety through improved training techniques. Clinical trials research has not been similarly scrutinised. The VALsartan In Acute myocardial iNfarcTion, a large multinational, pragmatic, randomised, double-blind, multicentre trial, was retrospectively evaluated for evidence of research conduct consistent with a performance "learning curve". DESIGN: Records provided protocol departure (deviations/violations) and documentation query data. For each site, analysis included patient order (eg, first, second), recruitment rate and first enrollment relative to study start date. SETTING: Computerised data from a trial coordinated by an academic research organisation collaborating with 10 academic and 2 commercial research organisations and an industry sponsor. Interventions 931 sites enrolled 14,703 patients. Departures were restricted to the first year. Exclusions included patient's death or loss to follow-up within 12 months and subjects enrolled 80th or higher at a site. Departures were assessed for variance with higher patient rank, more frequent recruitment and later start date. METHODS AND RESULTS: 12,367 patients at 931 sites were analysed. Departures were more common for patients enrolled earlier at a site (p<0.0001). For example, compared with the 30th patient, the first had 47% more departures. Departures were also more common with slower enrollment and site start closer to the trial start date (p<0.0001). Similar patterns existed for queries. CONCLUSIONS: Research performance improved during the VALsartan In Acute myocardial iNfarcTion consistent with a "learning curve". Although effects were not related to a change in outcome (mortality), learning curves in clinical research may have important safety, ethical, research quality and economic implications for trial conduct.

[Implementation of reperfusion therapy in ST segment elevation myocardial infarction (STEMI). A policy statement from the Belgian Society of Cardiology and its working group of acute cardiology and interventional cardiology]. / Mise en pratique du traitement de reperfusion dans les infarctus du myocarde avec élévation du segment ST (STEMI). Recommandations actualisées de la Société Belge de Cardiologie et de ses groupes de travail: le Groupe Interdisciplinaire de Cardiologie Aiguë (BIWAC) et le Groupe de Cardiologie Interventionnelle (BWGIC).

Myocardial infarction remains a major healthcare problem. Reperfusion therapy has been shown to influence favourably short- and long-term patient survival. The authors reviewed the data of early recognition of STEMI (ST Elevation Myocardial Infarction), the reperfusion modalities including a flowchart management, as proposed by the Belgian working groups (BIWAC and BWGIC), and the lessons learned from European and American registries. Primary PCI often remains the treatment of choice. A national policy is still required to implement the guidelines and improve clinical practice for our STEMI patients.

[Implementation of reperfusion therapy in ST segment elevation myocardial infarction (STEMI). A policy statement from the Belgian Society of Cardiology and its working group of acute cardiology and interventional cardiology]. / Mise en pratique du traitement de reperfusion dans les infarctus du myocarde avec élévation du segment ST.

Myocardial infarction remains a major healthcare problem. Reperfusion therapy has been shown to influence favourably short- and long-term patient survival. The authors reviewed the data of early recognition of STEMI (ST Elevation Myocardial Infarction), the reperfusion modalities including a flowchart management, as proposed by the Belgian working groups (BIWAC and BWGIC), and the lessons learned from European and American registries. Primary PCI often remains the treatment of choice. A national policy is still required to implement the guidelines and improve clinical practice for our STEMI patients.

Benefit of angiographic spontaneous reperfusion in STEMI: does it extend to diabetic patients?

BACKGROUND: Spontaneous reperfusion (SR) in ST elevation myocardial infarction (STEMI) improves clinical outcome, yet its incidence and impact among diabetic patients is unclear. OBJECTIVE: To carry out a systematic analysis of SR in the diabetic cohort of a large primary percutaneous coronary intervention (PCI)-treated population with STEMI. METHODS AND RESULTS: 4944 patients (15.5% diabetic) undergoing primary PCI in the APEX AMI study were evaluated. SR defined as pre-PCI Thrombolysis in Myocardial Infarction (TIMI) 3 flow occurred in 11.5% of patients; it was more common in non-diabetic (11.9%) than in diabetic patients (9.2%) (p = 0.028). Patients with SR versus no SR had improved post-PCI TIMI 3 flow: in non-diabetic patients (99.8% vs 90.3%, p<0.001) and in diabetic patients (98.6% vs 84.9%, p<0.001). Non-diabetic patients with SR showed a significant improvement in 90-day death/shock/congestive heart failure (CHF) compared with those without SR: 4.4% versus 8.9% (p = 0.001), respectively. The composite outcome in diabetic patients with versus without SR was 10.0% versus 14.9% (p = 0.270), respectively. When outcomes were examined according to tertiles of baseline blood glucose, both non-diabetic and diabetic patients with normoglycaemia showed higher SR rates (15.5%, 10.3%, 7.3% for non-diabetic patients, p<0.001; 17.4%, 7.2%, 9.1% for diabetic patients, p = 0.132), greater ST resolution (55.4%, 52.6%, 49.7% for non-diabetic patients, p = 0.030; 50%, 46.4%, 39.1% for diabetic patients, p = 0.179), and improved 90-day death/shock/CHF (5.2%, 8.3%, 14% for non-diabetic patients p<0.001; 8.7%, 4.2%, 15.8% for diabetic patients, p = 0.006). CONCLUSIONS: These data indicate that SR is less common in diabetic patients with STEMI. Diabetic patients without SR have worse post-PCI epicardial patency, which contributes to adverse outcomes. Diabetic patients with normal baseline blood glucose and SR have enhanced epicardial flow after PCI and improved prognosis.

The impact of fibrinolytic therapy for ST-segment-elevation acute myocardial infarction.

As privileged witnesses of the initiation and widespread use of reperfusion therapy the authors review the history of fibrinolytic therapy and of tissue-plasminogen activator (t-PA) more particularly and the current indications for its use in the era of mechanical reperfusion.

Short- and long-term outcomes following atrial fibrillation in patients with acute coronary syndromes with or without ST-segment elevation.

OBJECTIVE: To assess variables associated with the occurrence of atrial fibrillation (AF) and the relation of AF with short- and long-term outcomes and with other in-hospital complications in patients with acute coronary syndromes (ACS) with and without ST-segment elevation. DESIGN: Pooled database of 120 566 patients with ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation (NSTE) ACS enrolled in 10 clinical trials. Multivariable logistic regression and Cox proportional hazards modelling were used to identify factors associated with AF and its relation with clinical outcomes. SETTING: ACS complicated by AF. PATIENTS: 120,566 patients with STEMI and NSTE-ACS in 10 clinical trials. INTERVENTIONS: None evaluated. MAIN OUTCOME MEASURE: Short- and long-term mortality. RESULTS: Occurrence of AF was 7.5% in the overall population (STEMI 8.0% (n = 84 161); NSTE-ACS = 6.4% (n = 36,405)). Seven-day mortality was higher for patients with AF (5.1%) than for those without (1.6%). After adjusting for confounders, association of AF with 7-day mortality was present in STEMI (hazards ratio (HR) = 1.65; 95% CI 1.44 to 1.90) and NSTE-ACS (HR = 2.30; 95% CI 1.83 to 2.90; p interaction = 0.015). Risk of long-term mortality (day 8 to 1 year) was also higher in STEMI (HR = 2.37; 95% CI 1.79 to 3.15) and NSTE-ACS (HR = 1.67; 95% CI 1.41 to 1.99). AF had a larger impact in NSTE-ACS on risk of short-term mortality (p<0.001), stroke (p<0.001), ischaemic stroke (p<0.001) and moderate or severe bleeding (p<0.001). CONCLUSIONS: AF is more common in patients with STEMI. An association of AF with short- and long-term mortality among patients with STEMI and NSTE-ACS was found. Understanding these findings may lead to better care of patients with this common arrhythmia.

Risk stratification in ST-elevation myocardial infarction is enhanced by combining baseline ST deviation and subsequent ST-segment resolution.

BACKGROUND: The baseline sum of ST deviation (SigmaSTD) and ST segment resolution after fibrinolysis for ST-elevation myocardial infarction are prognostically useful. OBJECTIVES: To examine the prognostic impact of ST resolution after fibrinolysis and influence of baseline ST deviation in ASSENT-3. METHODS: ST resolution was determined in 4565 patients at 180 minutes after fibrinolysis. 30-Day and 1-year mortality was assessed in patients with complete (ie, > or =50%) versus incomplete ST resolution according to absolute baseline SigmaSTD. RESULTS: Patients with complete ST resolution had lower 30-day and 1-year mortality than those with incomplete ST resolution (3.7% vs 7.3%, p<0.001, and 6.1% vs 10.0%, p<0.001, respectively). After multivariable adjustment for key baseline risk factors, patients with anterior myocardial infarction (MI) in the highest quartile of SigmaSTD had a greater risk of 30-day and 1-year mortality than those in the lowest quartile in both complete (odds ratio (OR) = 2.34, 95% CI 1.14 to 4.80, and OR = 2.34, 95% CI 1.26 to 4.34, respectively) and incomplete ST resolution groups (OR = 4.97, 95% CI 1.82 to 13.61, and OR = 3.61, 95% CI 1.55 to 8.4, respectively). However, in patients with inferior MI this pattern only existed when ST resolution was incomplete (OR = 4.88, 95% CI 1.65 to 14.39, and OR = 4.34, 95% CI 1.66 to 11.37, respectively). CONCLUSION: These findings indicate that percentage ST resolution alone is an incomplete guide to 30-day and 1-year mortality. The integration of both the baseline and post-fibrinolysis ECG provides better risk assessment and can assist in the triage and treatment of such patients.

Relationship of treatment delays and mortality in patients undergoing fibrinolysis and primary percutaneous coronary intervention. The Global Registry of Acute Coronary Events.

OBJECTIVE: Treatment delays may result in different clinical outcomes in patients with ST-segment elevation myocardial infarction (STEMI) who receive fibrinolytic therapy vs primary percutaneous coronary intervention (PCI). The aim of this analysis was to examine how treatment delays relate to 6-month mortality in reperfusion-treated patients enrolled in the Global Registry of Acute Coronary Events (GRACE). DESIGN: Prospective, observational cohort study. SETTING: 106 hospitals in 14 countries. PATIENTS: 3959 patients who presented with STEMI within 6 h of symptom onset and received reperfusion with either a fibrin-specific fibrinolytic drug or primary PCI. MAIN OUTCOME MEASURES: 6-month mortality. METHODS: Multivariable logistic regression was used to assess the relationship between outcomes and treatment delay separately in each cohort, with time modelled with a quadratic term after adjusting for covariates from the GRACE risk score. RESULTS: A total of 1786 (45.1%) patients received fibrinolytic therapy, and 2173 (54.9%) underwent primary PCI. After multivariable adjustment, longer treatment delays were associated with a higher 6-month mortality in both fibrinolytic therapy and primary PCI patients (p<0.001 for both cohorts). For patients who received fibrinolytic therapy, 6-month mortality increased by 0.30% per 10-min delay in door-to-needle time between 30 and 60 min compared with 0.18% per 10-min delay in door-to-balloon time between 90 and 150 min for patients undergoing primary PCI. CONCLUSIONS: Treatment delays in reperfusion therapy are associated with higher 6-month mortality, but this relationship may be even more critical in patients receiving fibrinolytic therapy.

Variations in the use of emergency PCI for the treatment of re-infarction following intravenous fibrinolytic therapy: impact on outcomes in HERO-2.

BACKGROUND: Patients who suffer re-infarction during initial hospitalization for ST-elevation myocardial infarction (STEMI) have decreased survival compared to patients without re-infarction, so treatment of re-infarction may influence survival. METHODS AND RESULTS: To determine whether the utilization of reperfusion therapies varied within 12 h of re-infarction and was associated with 30-day mortality, we studied 552 patients with re-infarction of 17,073 patients with STEMI enrolled in HERO-2 in five regions (Russia, Eastern Europe, Western Countries, Asia, and Latin America). Patients presenting within 6 h of symptom-onset were randomized to receive either bivalirudin or unfractionated heparin intravenously just prior to streptokinase. Re-infarction occurred in 2.8 and 3.6% of bivalirudin and heparin treated patients, respectively (P = 0.004), but treatment assignment did not influence mortality after re-infarction. Patients with re-infarction had a higher 30-day mortality than those without re-infarction (24 vs. 10%; P < 0.001 by Cox model). Within 12 h of re-infarction, fibrinolytic therapy was administered to 12.0 and 8.2% underwent percutaneous coronary intervention (PCI); these two treatments were more frequently utilized in patients from Western countries (n = 112), compared to patients from other countries (n = 440) (34.8 and 16.1% compared to 6.1 and 6.1%, respectively, P < 0.001). Mortality was 15% in patients receiving reperfusion therapy for re-infarction and 27% for those with conservative management, hazard ratio (HR) 0.53 (95% CI 0.32-0.88), P = 0.01. In multiple Cox regression analysis which included adjustment for clinical variables and randomized treatment assignment, 30-day mortality after re-infarction varied by region (highest Latin America 29%, lowest Western countries 15%; P = 0.01). Other independent prognostic factors included age, time from randomization to re-infarction, and Killip class at randomization. The HR for PCI treatment of re-infarction was 0.18 [(95% CI 0.04-0.76), P = 0.02] in analyses which excluded deaths within 12 h. CONCLUSION: Treatment of re-infarction with reperfusion therapies was markedly under-utilized, especially in non-western countries. PCI for re-infarction, in particular, was associated with a lower 30-day mortality, which may reflect both patient selection and effects of treatment.

Intervention in acute coronary syndromes: do patients undergo intervention on the basis of their risk characteristics? The Global Registry of Acute Coronary Events (GRACE).

OBJECTIVE: To determine whether revascularisation is more likely to be performed in higher-risk patients and whether the findings are influenced by hospitals adopting more or less aggressive revascularisation strategies. METHODS: GRACE (Global Registry of Acute Coronary Events) is a multinational, observational cohort study. This study involved 24,189 patients enrolled at 73 hospitals with on-site angiographic facilities. RESULTS: Overall, 32.5% of patients with a non-ST elevation acute coronary syndrome (ACS) underwent percutaneous coronary intervention (PCI; 53.7% in ST segment elevation myocardial infarction (STEMI)) and 7.2% underwent coronary artery bypass grafting (CABG; 4.0% in STEMI). The cumulative rate of in-hospital death rose correspondingly with the GRACE risk score (variables: age, Killip class, systolic blood pressure, ST segment deviation, cardiac arrest at admission, serum creatinine, raised cardiac markers, heart rate), from 1.2% in low-risk to 3.3% in medium-risk and 13.0% in high-risk patients (c statistic = 0.83). PCI procedures were more likely to be performed in low- (40% non-STEMI, 60% STEMI) than medium- (35%, 54%) or high-risk patients (25%, 41%). No such gradient was apparent for patients undergoing CABG. These findings were seen in STEMI and non-ST elevation ACS, in all geographical regions and irrespective of whether hospitals adopted low (4.2-33.7%, n = 7210 observations), medium (35.7-51.4%, n = 7913 observations) or high rates (52.6-77.0%, n = 8942 observations) of intervention. CONCLUSIONS: A risk-averse strategy to angiography appears to be widely adopted. Proceeding to PCI relates to referral practice and angiographic findings rather than the patient's risk status. Systematic and accurate risk stratification may allow higher-risk patients to be selected for revascularisation procedures, in contrast to current international practice.

Inhibition of complement activation by pexelizumab reduces death in patients undergoing combined aortic valve replacement and coronary artery bypass surgery.

OBJECTIVE: We sought to evaluate the effects of pexelizumab, a C5 complement inhibitor, on death and myocardial infarction in patients undergoing combined aortic valve replacement and coronary artery bypass grafting surgery. METHODS: The Pexelizumab for Reduction in Myocardial Infarction and Mortality in Coronary Artery Bypass Graft surgery trial, a phase III prospective, randomized, double-blind, placebo-controlled study, enrolled 3099 patients at 205 centers. The primary end point was the composite of death, myocardial infarction, or both at postoperative day 30 in patients undergoing coronary artery bypass grafting without valve surgery. Postoperative myocardial infarction was defined as a creatine kinase MB fraction value of 100 ng/mL or greater, Q-wave myocardial infarction with a creatine kinase MB fraction value of 70 ng/mL or greater, or new Q-wave evidence of myocardial infarction by postoperative day 30. Because patients undergoing coronary artery bypass grafting with a valve procedure were not included in the primary population, separate analysis of death and myocardial infarction was conducted in 218 patients undergoing combined aortic valve replacement and coronary artery bypass grafting surgery. RESULTS: Of the 353 patients randomized to any valve procedure, 106 (61%) underwent combined aortic valve replacement and coronary artery bypass grafting in the pexelizumab treatment group compared with 112 (63%) patients in the placebo group. Coronary artery bypass grafting was performed with 1 or more internal thoracic artery grafts in 139 (64%) patients and with 1 or more saphenous vein grafts in 179 (82%) patients. There were 4 (3.8%) deaths in the pexelizumab group versus 11 (9.9%) in the placebo group by postoperative day 30 and 6 (5.7%) deaths in the active group versus 16 (14.4%) in the placebo group by postoperative day 180 (P =.107 and P =.043, respectively, Fisher exact test). The incidence of myocardial infarction 30 days after surgical intervention was identical in the 2 groups, but the study was not designed to detect differences in this cohort of patients. CONCLUSIONS: Inhibition of complement activation by pexelizumab resulted in a decreased mortality at 180 days among 218 patients who underwent combined aortic valve replacement and coronary artery bypass grafting surgery. Additional studies are warranted to confirm this decrease in mortality with pexelizumab in combined aortic valve replacement and coronary artery bypass grafting procedures.

Relation between baseline risk and treatment decisions in non-ST elevation acute coronary syndromes: an examination of international practice patterns.

OBJECTIVES: To examine the interaction between ST segment depression on the baseline ECG and subsequent in-hospital revascularisation on six month mortality among patients with non-ST elevation acute coronary syndromes. To examine whether ST segment depression influenced clinical decision making and whether there was international variation in the use of cardiac procedures across ST segment depression categories. METHODS: 11 453 patients enrolled in GUSTO-IIB (global use of strategies to open occluded coronary arteries), PARAGON (platelet IIb/IIIa antagonism for the reduction of acute coronary syndrome events in a global organisation network) -A, and PARAGON-B were studied. Patients were categorised as having no ST segment depression, 1 mm ST segment depression in two contiguous leads, and ST segment depression > or = 2 mm in two contiguous leads. International practice across four geographic regions was examined: USA, Canada, Europe, and Australia/New Zealand. RESULTS: Revascularisation appeared to have no impact on survival among patients with no ST segment depression; however, revascularisation was associated with a significant survival benefit among patients with ST segment depression > or = 1 mm. There was an inverse relation between the extent of ST segment depression and the use of angiography as well as angioplasty (p < 0.01). However, patients with ST segment depression > or = 2 mm were more likely to undergo bypass surgery. The only significant trend of increasing use of revascularisation procedures with increasing ST segment depression was observed in the USA. CONCLUSIONS: International practice patterns in procedure use appear to be insensitive to the extent of ST segment depression. Major opportunities for more efficient delivery of care exist in all regions.

Time to treatment and the impact of a physician on prehospital management of acute ST elevation myocardial infarction: insights from the ASSENT-3 PLUS trial.

OBJECTIVES: To assess the impact of variation in prehospital care across distinct health care environments in ASSENT (assessment of the safety and efficacy of a new thrombolytic) -3 PLUS, a large (n = 1639) contemporary multicentred international trial of prehospital fibrinolysis. Specifically, the objectives were to assess predictors of time to treatment, whether components of time to treatment vary across countries, and the impact of physician presence before hospitalisation on time to treatment, adherence to protocol, and clinical events. METHODS: Patient characteristics associated with early treatment (< or = 2 hours), comparison of international variation in time to treatment, and components of delay were assessed. Trial specific patient data were linked with site specific survey responses. RESULTS: Younger age, slower heart rate, lower systolic blood pressure, and prior percutaneous coronary intervention were associated with early treatment. Country of origin accounted for the largest proportion of variation in time. Intercountry heterogeneity was shown in components of elapsed time to treatment. Physicians in the prehospital setting enrolled 63.8% of patients. The presence of a physician was associated with greater adherence to protocol mandated treatments and procedures but with delay in time to treatment (120 v 108 minutes, p < 0.001). CONCLUSION: Country of enrollment accounted for the largest proportion of variation in time to treatment and intercountry heterogeneity modulated components of delay. The effectiveness and safety of prehospital fibrinolysis was not influenced by the presence of a physician. These data, acquired in diverse health care environments, provide new understanding into the components of prehospital treatment delay and the opportunities to further reduce time to fibrinolysis for patients with ST elevation myocardial infarction.

Responsiveness to inhaled nitric oxide is a predictor for mid-term survival in adult patients with congenital heart defects and pulmonary arterial hypertension.

BACKGROUND: It was previously demonstrated that in adults with congenital heart disease and pulmonary arterial hypertension and/or the Eisenmenger syndrome, the pulmonary circulation remained responsive to inhaled nitric oxide (iNO). We wanted to evaluate whether the responsiveness to iNO was related to mid-term outcome in these patients. METHODS: In 21 consecutive patients, total pulmonary vascular resistance (TPR) was measured at baseline, after 5 min iNO (80 ppm), and after NO withdrawal. Patients were considered responders when TPR was reduced by at least 20% during NO inhalation or when TPR increased by more than 10% after NO withdrawal. Responders and non-responders were followed prospectively and the primary endpoint of the study was cardiopulmonary death, the secondary endpoint the combination of death, need for treatment with prostacyclin or heart-lung transplantation. Kaplan-Meier survival curves for both groups were plotted and compared using log rank testing. RESULTS: Ten patients were considered responders (four male, median age 25 years, Q1 19 and Q3 66 years), while 11 patients did not respond (two male, median age 27 years, Q1 18 and Q3 40 years). The median follow-up time of the total group was 5.0 years (Q1 3.2 and Q3 5.7 years). Four of the non-responders died a cardiovascular death; none of the responders died. The difference in survival between responders and non-responders was statistically significant. For the secondary endpoint, no significant differences were found between both groups. CONCLUSIONS: The responsiveness to inhaled NO in adult patients with pulmonary arterial hypertension and/or the Eisenmenger syndrome is related to mid-term outcome. These findings might be important for risk stratification and the choice of treatment in this specific patient population.

Atrial fibrillation after radiofrequency ablation of atrial flutter: preventive effect of angiotensin converting enzyme inhibitors, angiotensin II receptor blockers, and diuretics.

OBJECTIVES: To determine risk factors for the development of atrial fibrillation (AF) after atrial flutter (AFL) ablation; and to study the relation between AF development and periprocedural drug use. METHODS: AFL ablation was performed in 196 patients. The relation between AF occurrence and clinical, echocardiographic, and procedural factors and periprocedural drug use was analysed retrospectively by a Cox proportional hazard method. RESULTS: After a median follow up of 2.2 years, 114 patients (58%) developed at least one AF episode. Factors associated with AF development were the presence of preprocedural AF, a history of cardioversion, and the number of antiarrhythmic drugs used before the procedure. Use of angiotensin converting enzyme (ACE) inhibitors/angiotensin II receptor blockers and diuretics was significantly associated by univariate and multivariate analyses with less development of AF. CONCLUSIONS: A high proportion of patients develop AF after AFL ablation. The incidence of AF is related to pre-ablation AF and its persistence. ACE inhibitors/angiotensin II receptor blockers and diuretics seem to protect against AF.

Will oral antithrombin agents replace warfarin?

The new oral direct thrombin inhibitor ximelagatran is at least equivalent to warfarin for stroke prevention in patients with non-valvar atrial fibrillation, and seems to be a promising adjunct to aspirin after acute coronary syndrome