The effect of interleukin-1 receptor antagonist therapy on markers of inflammation in non-ST elevation acute coronary syndromes: the MRC-ILA Heart Study.

AIMS: Acute coronary syndromes (ACSs) are driven by inflammation within coronary plaque. Interleukin-1 (IL-1) has an established role in atherogenesis and the vessel-response to injury. ACS patients have raised serum markers of inflammation. We hypothesized that if IL-1 is a driving influence of inflammation in non-ST elevation ACS (NSTE-ACS), IL-1 inhibition would reduce the inflammatory response at the time of ACS. METHODS AND RESULTS: A phase II, double-blinded, randomized, placebo-controlled, study recruited 182 patients with NSTE-ACS, presenting <48 h from onset of chest pain. Treatment was 1:1 allocation to daily, subcutaneous IL-1receptor antagonist (IL-1ra) or placebo for 14 days. Baseline characteristics were well matched. Treatment compliance was 85% at 7 days. The primary endpoint (area-under-the-curve for C-reactive protein over the first 7 days) was: IL-1ra group, 21.98 mg day/L (95%CI 16.31-29.64); placebo group, 43.5 mg day/L (31.15-60.75) (geometric mean ratio = 0.51 mg/L; 95%CI 0.32-0.79; P = 0.0028). In the IL-1ra group, 14-day achieved high-sensitive C-reactive protein (P < 0.0001) and IL-6 levels (P = 0.02) were lower than Day 1. Sixteen days after discontinuation of treatment (Day 30) high-sensitive C-reactive protein levels had risen again in the IL-1ra group [IL-1ra; 3.50 mg/L (2.65-4.62): placebo; 2.21 mg/L (1.67-2.92), P = 0.022]. MACE at Day 30 and 3 months was similar but at 1 year there was a significant excess of events in the IL-1ra group. CONCLUSION: IL-1 drives C-reactive protein elevation at the time of NSTE-ACS. Following 14 days IL-1ra treatment inflammatory markers were reduced. These results show the importance of IL-1 as a target in ACS, but also indicate the need for additional studies with anti-IL-1 therapy in ACS to assess duration and safety. CLINICAL TRIAL REGISTRATION EUCTR: 2006-001767-31-GB: www.clinicaltrialsregister.eu/ctr-search/trial/2006-001767-31/GB.

Serum sphingolipids level as a novel potential marker for early detection of human myocardial ischaemic injury.

BACKGROUND: Ventricular tachyarrhythmias are the most common and often the first manifestation of coronary heart disease and lead to sudden cardiac death (SCD). Early detection/identification of acute myocardial ischaemic injury at risk for malignant ventricular arrhythmias in patients remains an unmet medical need. In the present study, we examined the sphingolipids level after transient cardiac ischaemia following temporary coronary artery occlusion during percutaneous coronary intervention (PCI) in patients and determined the role of sphingolipids level as a novel marker for early detection of human myocardial ischaemic injury. METHODS AND RESULTS: Venous samples were collected from either the coronary sinus (n = 7) or femoral vein (n = 24) from 31 patients aged 40-73 years-old at 1, 5 min, and 12 h, following elective PCI. Plasma sphingolipids levels were assessed by HPLC. At 1 min coronary sinus levels of sphingosine 1-phosphate (S1P), sphingosine (SPH), and sphinganine (SA) were increased by 314, 115, and 614%, respectively (n = 7), while peripheral blood levels increased by 79, 68, and 272% (n = 24). By 5 min, coronary sinus S1P and SPH levels increased further (720%, 117%), as did peripheral levels of S1P alone (792%). Where troponin T was detectable at 12 h (10 of 31), a strong correlation was found with peak S1P (R (2) = 0.818; P < 0.0001). CONCLUSION: For the first time, we demonstrate the behavior of plasma sphingolipids following transient cardiac ischaemia in humans. The observation supports the important role of sphingolipids level as a potential novel marker of transient or prolonged myocardial ischaemia.

Transcatheter interventions for multiple lesions in adults with congenital heart disease.

Recent advances in diagnosis, surgery and interventional management have significantly changed the quality of life of patients with congenital heart disease. Historically, congenital heart disease patients with multiple cardiac lesions have been referred for surgery; however, with the advent of newer technologies and expertise, transcatheter treatment has evolved as an alternative option. A series of patients who underwent interventional procedures for multiple congenital heart disease lesions with excellent procedural and medium-term outcomes is reported.

The pressure wire as a diagnostic tool in patients with congenital cardiac disease.

The pressure wire has emerged as a useful tool to assess the clinical severity of moderate coronary artery lesions. We report a novel use of the pressure wire in adult patients with complex congenital cardiac disease in whom it was used in assessing pressures beyond the stenosis in the distal pulmonary artery, aorto-pulmonary collaterals, and across prosthetic tricuspid valves, where conventional catheters were unable to reach. We used this in three of our patients for assessment of pulmonary artery pressures and in two patients for assessment of pressures across a prosthetic St Jude® valve. Out of the three patients referred for assessment, only two had significantly raised distal pulmonary pressures enabling them to receive appropriate therapy. Out of the two patients with a prosthetic tricuspid valve, only one required surgery based on this assessment. We describe a novel use of the pressure wire in the functional assessment of adults with congenital cardiac disease in whom conventional catheter techniques may not be able to provide adequate data. It can be a guide to provide appropriate therapy and avoid unnecessary interventions in this patient group.

A comparison of drug-eluting stents versus bare metal stents in saphenous vein graft PCI outcomes: a meta-analysis.

AIMS: Studies demonstrate that percutaneous coronary intervention (PCI) with drug-eluting stents (DES) is associated with reduced revascularization and major adverse cardiac events (MACE) rates compared to bare metal stents (BMS) in native coronary vessels. Optimal PCI treatment of saphenous vein graft (SVG) lesions remains unclear despite SVG procedures representing up to 10% of PCI cases. We therefore performed a meta-analysis to compare outcomes between BMS and DES in SVG PCI. METHODS AND RESULTS: A search (2004-2009) of MEDLINE and conference proceedings for all relevant studies comparing mortality and MACE outcomes in DES versus BMS in SVG PCI and meta-analysis of the data was performed. Twenty studies were identified from 2005 to 2009 enrolling a total of 5,296 patients. Meta-analysis revealed a decrease in mortality associated with DES use, odds ratio (OR) 0.68; 95% confidence interval (CI) 0.53-0.88; P = 0.004. Similarly, MACE (OR 0.64; 95% CI 0.51-0.82; P < 0.001), total lesion revascularization (OR 0.60; 95% CI 0.43-0.83; P = 0.002), and total vessel revascularization (OR 0.57; 95% CI 0.41-0.80; P = 0.001) were significantly decreased in the patients in which DES were used compared to BMS. This reduction in mortality and MACE events associated with DES use appears to be limited to registry studies and not randomized controlled studies. CONCLUSIONS: Our meta-analysis suggests DES use to be safe in SVG PCI and associated with reduced mortality and MACE rates with reductions in revascularization also observed.

Aortic balloon valvuloplasty: is there still a role in high-risk patients in the era of percutaneous aortic valve replacement?

OBJECTIVES: To assess procedural and clinical outcomes in adults with severe aortic stenosis (AS) undergoing percutaneous aortic balloon valvuloplasty (PABV), who are considered unsuitable on initial assessment for surgical aortic valve replacement or transcatheter aortic valve implantation (TAVI). BACKGROUND: Surgical valve replacement provides better outcomes than conservative treatment for patients with severe symptomatic AS; however, patients with multiple comorbidities or hemodynamic instability carry a high operative risk. While TAVI offers an alternative to surgery, not all patients are suitable. This study looks at medium-term outcomes in a series of high-risk patients undergoing PABV. METHODS: Pre- and postprocedure aortic valve gradients were measured by catheterization and echocardiography. Patients were assessed for symptomatic benefit and clinical outcomes. RESULTS: Over 4 years, 42 patients underwent PABV. Mean clinical follow-up was 8 +/- 5.8 months and survival was 63%. Mean echocardiographic aortic valve gradient fell from 84.6 +/- 27 mmHg to 51.3 +/- 16 mmHg (p < 0.05). In 29% (12/42) patients, PABV was performed as a bridge to definitive AVR. Four had surgical AVR and six had TAVI. Two had successful noncardiac surgery. Four patients died in the periprocedural period and all were in cardiogenic shock. Patients were in New York Heart Association (NYHA) class IV decreased from 60% to 5% postprocedure (p < 0.05). CONCLUSION: PABV is useful as a palliation or bridge to definitive therapy for treatment of patients with severe AS unsuitable for surgery. It is associated with good medium-term cardiac outcomes and enables some patients to receive definitive therapy.

Traumatic aortic dissection and coronary fistula treated with transcatheter management.

An adolescent male presented with a dissection of the thoracic aorta and a left anterior descending coronary artery to right ventricular fistula following a road traffic accident. Authors report the management of this patient using a transcatheter approach for both these arterial issues, with stenting to the thoracic aorta and coil embolization of the coronary artery to right ventricular fistula as a staged procedure, along with a brief review of the literature on traumatic arterial injuries.

Recurrent acute rheumatic fever: a forgotten diagnosis?

The incidence of acute rheumatic fever has seen a dramatic decline over the last 15 to 20 years in most developed countries and treatment of this disease has changed little since. The ease of travel and immigration and the cosmopolitan nature of many cities mean that occasionally the disease will come to the attention of clinicians not familiar with its presentation, resulting in delayed diagnosis and treatment. We present a case of recurrent acute rheumatic fever in a patient who was initially thought to be suffering from acute bacterial endocarditis on her previously diseased rheumatic aortic valve. This culminated in her undergoing urgent aortic valve replacement during a phase of the illness that should have been treated with high dose anti-inflammatory medication. Therefore, clinicians should be aware of this condition and include it in their differential diagnosis of the febrile patient with a previous history of rheumatic fever. We briefly discuss the diagnostic dilemma of patients suffering from this condition and in differentiating it from acute endocarditis.