A Selection of Recent Papers as Recommended by the Advisory Panel

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Prevalence of Long-QT Syndrome Gene Variants in Sudden Infant Death Syndrome
Arnestad M, et al.
Circulation, 2007;115(3):361–7.

There are inadequate data regarding the true prevalence of mutations in arrhythmia-susceptibility genes among sudden infant death syndrome (SIDS) cases. Given the importance and potential implications of these observations, the authors performed a study to more accurately quantify the contribution to SIDS of long-QT syndrome (LQTS) gene mutations and rare variants. Molecular screening of seven genes with LQTS was performed from 201 cases diagnosed as SIDS according to the Nordic Criteria. Mutations and rare variants were found in 26 of 201 cases (12.9%). On the basis of their functional effect, however, the authors considered eight mutations and seven rare variants found in 19 of 201 cases as likely contributors to sudden death.

The authors demonstrated that 9.5% of cases diagnosed as SIDS carry functionally significant genetic variants in LQTS genes. This demonstrates that sudden arrhythmic death is an important contributor to SIDS. As these variants likely modify ventricular repolarisation and QT interval duration, these results support the debated concept that an ECG would probably identify most infants at risk of sudden death due to LQTS either in infancy or later in life. 

Prevalence and Prognosis of Left Ventricular Systolic Dysfunction in Asymptomatic Diabetic Patients without Known Coronary Artery Disease Referred for Stress Single-photon Emission Computed Tomography and Assessment of Left Ventricular Function
Chareonthaitawee P, et al.
Am Heart J, 2007;154(3):567–74.

The prevalence and prognosis of reduced left ventricular ejection fraction (LVEF) in asymptomatic diabetic patients without known coronary artery disease (CAD) are not known. The authors examined 1,046 asymptomatic diabetic patients (age 60±13 years, 69% male) without known CAD, referred for stress single-photon emission computed tomography (SPECT) and assessment of LVEF. Patients were stratified according to the presence of normal LVEF, mildly reduced LVEF or moderately/ severely reduced LVEF. SPECT images were classified as low-, intermediate- or high-risk based on the summed stress score. The mean follow-up was 5.3±3.3 years.

The prevalence of reduced LVEF was 16.7%. This group was older and had more peripheral arterial disease and a higher prevalence of electrocardiographic Q waves than those without reduced LVEF. Mean summed stress, summed reversibility and summed rest scores were significantly more abnormal in the reduced LVEF group, as was high-risk summed stress score. Survival was significantly lower in patients with any reduction in LVEF compared with those without reduced LVEF. By multivariate analysis, reduced LVEF was independently associated with increased mortality. In this population of asymptomatic diabetic patients without known CAD referred for stress SPECT, one in six patients had reduced LVEF. Most of these patients had intermediate/ high-risk SPECT scans. The annual mortality rates of the groups with and without reduced LVEF were 7 and 4%, respectively.

Molecular Imaging of Inflammation in Atherosclerosis with Targeted Ultrasound Detection of Vascular Cell Adhesion Molecule-1
Kaufmann BA, et al.
Circulation, 2007;116;276–84.

The authors hypothesised that molecular imaging of vascular cell adhesion molecule-1 (VCAM-1) expression with contrast-enhanced ultrasound (CEU) could be used to image vascular inflammatory responses for early diagnosis of atherosclerosis. Attachment of VCAM-1–targeted and control microbubbles to cultured endothelial cells was assessed in a flow chamber at variable shear stress.

Microbubble attachment to aortic plaque was determined by en face microscopy of the thoracic aorta 10 minutes after intravenous injection in wild-type or apolipoprotein E-deficient mice on either chow or hyper-cholesterolemic diet. VCAM-1-targeted but not control microbubbles attached to cultured endothelial cells, although there was firm attachment at the highest shear rates only in pulsatile flow conditions. Aortic attachment of microbubbles and targeted CEU signal was very low in control wild-type mice on chow diet. Aortic attachment of microbubbles and CEU signal for VCAM-1-targeted microbubbles differed between treatment groups according to the extent of VCAM-1-positive plaque formation. CEU molecular imaging of VCAM-1 is capable of rapidly quantifying vascular inflammatory changes that occur in different stages of atherosclerosis. This method may be useful for early risk stratification according to inflammatory phenotype.

Diastolic Stiffness of the Failing Diabetic Heart: Importance of Fibrosis, Advanced Glycation End Products and Myocyte Resting Tension
van Heerebeek L, et al.
Circulation, 2008;117;43–51.

The contribution to diastolic stiffness of fibrosis, advanced glycation end-products (AGEs) and cardiomyocyte resting tension was assessed in diabetic heart failure patients with normal or reduced left ventricular ejection fraction (LVEF). Left ventricular endomyocardial biopsy samples were procured in 28 patients with normal LVEF and in 36 patients with reduced LVEF, all without coronary artery disease. Sixteen patients with normal LVEF and 10 with reduced LVEF had diabetes mellitus. Biopsy samples were used for quantification of collagen and AGEs and for isolation of cardiomyocytes to measure resting tension. Diabetic heart failure patients had higher diastolic left ventricular stiffness irrespective of LVEF.

Diabetes mellitus increased the myocardial collagen volume fraction only in patients with reduced LVEF and increased cardiomyocyte resting tension only in patients with normal LVEF. Diabetes increased myocardial AGE deposition in patients with reduced LVEF and less so in patients with normal LVEF. Mechanisms responsible for the increased diastolic stiffness of the diabetic heart differ in heart failure with reduced and normal LVEF: fibrosis and AGEs are more important when LVEF is reduced, whereas cardiomyocyte resting tension is more important when LVEF is normal.