AimsTo collect information on the use of the Reveal implantable loop recorder (ILR) in the patient care pathway and to investigate its effectiveness in the diagnosis of unexplained recurrent syncope in everyday clinical practice.Methods and resultsProspective, multicentre, observational study conducted in 2006–2009 in 10 European countries and Israel. Eligible patients had recurrent unexplained syncope or pre-syncope. Subjects received a Reveal Plus, DX or XT. Follow up was until the first recurrence of a syncopal event leading to a diagnosis or for ≥1 year. In the course of the study, patients were evaluated by an average of three different specialists for management of their syncope and underwent a median of 13 tests (range 9–20). Significant physical trauma had been experienced in association with a syncopal episode by 36% of patients. Average follow-up time after ILR implant was 10 ± 6 months. Follow-up visit data were available for 570 subjects. The percentages of patients with recurrence of syncope were 19, 26, and 36% after 3, 6, and 12 months, respectively. Of 218 events within the study, ILR-guided diagnosis was obtained in 170 cases (78%), of which 128 (75%) were cardiac.ConclusionA large number of diagnostic tests were undertaken in patients with unexplained syncope without providing conclusive data. In contrast, the ILR revealed or contributed to establishing the mechanism of syncope in the vast majority of patients. The findings support the recommendation in current guidelines that an ILR should be implanted early rather than late in the evaluation of unexplained syncope.

AimsThis study evaluates the agreement between echocardiographic and cardiac magnetic resonance (CMR) imaging data, and the impact a discrepancy between the two may have on the clinical diagnosis of arrhythmogenic right ventricular cardiomyopathy (ARVC). Methods and resultsFrom the Nordic ARVC Registry, 102 patients with definite ARVC who had undergone both echocardiography and CMR were included (median age 42 + 16 years, 36% female, 78% probands). Patients were divided into two groups according to CMR-positive or -negative criteria, and the echocardiographic data were compared between the two. There were 72 CMR-positive patients. They had significantly larger RV dimensions and lower fractional area change on echocardiography compared with CMR-negative patients; parasternal long-axis right ventricular outflow tract (RVOT) 37 + 7 vs. 32 + 5 mm, parasternal short-axis RVOT 38 + 7 vs. 32 + 6 mm, fractional area shortening 31 + 9 vs. 39 + 9% (P , 0.003 for all). Only 36 (50%) of the CMR-positive patients fulfilled ARVC criteria by echocardiography, hence the diagnostic performance was low; sensitivity 50% and specificity 70%, positive predictive value 80% and negative predictive value 37%. Individuals with regional wall abnormalities on CMR were more likely to have ventricular arrhythmias (77 vs. 57%, P ¼ 0.047). ConclusionA significant proportion of patients with imaging-positive ARVC by CMR did not fulfil echocardiographic ARVC 2010 criteria. These findings confirm that echocardiographic evaluation of subtle structural changes in the right ventricle may be unreliable, and the diagnostic performance of CMR compared with echocardiography should be reflected in the guidelines.--

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C aveolae are small (50-100 nm in size) plasma invaginations with a cup-like shape 1 and a composition of cholesterol and other lipids that classify them as lipid rafts. These rafts are enriched in a large number of protein complexes involved in signaling and vesicular trafficking. Editorial see p 439 Clinical Perspective on p 461Mutations in the CAV3 gene, coding for caveolin-3, are associated with a variety of muscle diseases (ie, rippling muscle disease, 3 limb-girdle-muscle dystrophy, 4 muscular dystrophy, 5,6 and cardiomyopathy). 7,8 Most recently, mutations in CAV3 have been found to be associated with long-QT syndrome-9 (LQTS9; Figure 1). [9][10][11] Caveolae are structurally composed of caveolins, a family of proteins comprising caveolin-1, caveolin-2, and caveolin-3 in humans. They exhibit a ubiquitous tissue distribution; however, caveolin-3 is selectively expressed in the caveolae of heart and skeletal muscle. 2,12,13 Caveolin-3 comprises 151 amino acids and is divided into 4 domains; the N-terminal domain contains the FEDVIAEP caveolin signature domain ( Figure 1). The transmembrane domain loops through the membrane, and both the N and C termini are cytoplasmic. After homo-oligomerization, which occurs in the endoplasmic reticulum, caveolin-3 forms caveolar complexes that subsequently fuse with the plasma membrane to form the caveolae. 13 The scaffolding domain is essential for the homo-oligomerization of caveolin-3.Background-Mutations in CAV3, coding for caveolin-3, the major constituent scaffolding protein of cardiac caveolae, have been associated with skeletal muscle disease, cardiomyopathy, and most recently long-QT syndrome (LQTS) and sudden infant death syndrome. We examined the occurrence of CAV3 mutations in a large cohort of patients with LQTS. Methods and Results-Probands with LQTS (n=167) were screened for mutations in CAV3 using direct DNA sequencing.A single proband (0.6%) was found to be a heterozygous carrier of a previously described missense mutation, caveolin-3:p.T78M. The proband was also a heterozygous carrier of the trafficking-deficient Kv11.1:p.I400N mutation. The caveolin-3:p.T78M mutation was found isolated in 3 family members, none of whom had a prolonged QT c interval.Coimmunoprecipitations of caveolin-3 and the voltage-gated potassium channel subunit (Kv11.1) were performed, and the electrophysiological classification of the Kv11.1 mutant was carried out by patch-clamp technique in human embryonic kidney 293 cells. Furthermore, the T-wave morphology was assessed in mutation carriers, double mutation carriers, and nonmutation carriers by applying a morphology combination score. The morphology combination score was normal for isolated caveolin-3:p.T78M carriers and of LQT2 type in double heterozygotes. Conclusions-Mutations in CAV3 are rare in LQTS. Furthermore, caveolin-3:p.T78M did not exhibit a LQTS phenotype.Because no association has ever been found between LQTS and isolated CAV3 mutations, we suggest that LQTS9 is considered a provisional entity.