Medium-chain acyl-CoA dehydrogenase deficiency (MCADD) represents a potentially fatal fatty acid beta-oxidation disorder. Newborn screening (NBS) by tandem mass spectrometry (MS/MS) has been implemented worldwide, but is associated with unresolved questions regarding population heterogeneity, burden on healthy carriers, cut-off policies, false-positive and negative rates. In a retrospective case-control study, 333 NBS samples showing borderline acylcarnitine patterns but not reaching recall criteria were genotyped for the two most common mutations (c.985A>G/c.199C>T) and compared with genotypes and acylcarnitines of 333 controls, 68 false-positives, and 34 patients. c.985A>G was more frequently identified in the study group and false-positives compared to controls (1:4.3/1:2.3 vs. 1:42), whereas c.199C>T was found more frequently only within the false-positives (1:23). Biochemical criteria were devised to differentiate homozygous (c.985A>G), compound heterozygous (c.985A>G/c.199C>T), and heterozygous individuals. Four false-negatives were identified because our initial algorithm required an elevation of octanoylcarnitine (C(8)) and three secondary markers in the initial and follow-up sample. The new approach allowed a reduction of false-positives (by defining high cut-offs: 1.4 micromol/l for C(8); 7 for C(8)/C(12)) and false-negatives (by sequencing the ACADM gene of few suspicious samples). Our validation strategy is able to differentiate healthy carriers from patients doubling the positive predictive value (42-->88%) and to target NBS to MCADD-subsets with potentially higher risk of adverse outcome. It remains controversial, if NBS programs should aim at identifying all subsets of all diseases included. Because the natural course of milder variants cannot be assessed by observational studies, our strategy could serve as a general model for evaluation of MS/MS-based NBS.
Funding Acknowledgements Type of funding sources: None. Background Pulmonary vein isolation (PVI) is an effective treatment strategy in symptomatic atrial fibrillation (AF) patients. However, this approach shows worse long-term results in individuals suffering from persistent compared to the paroxysmal type. Purpose The objective was to investigate differences of left atrial (LA) as well as left atrial appendage (LAA) anatomy in persistent AF (persAF) and paroxysmal (PAF) and patients. Methods An observational single center study with a blinded retrospective analysis of cardiac computed tomography angiography (CCTA) images was conducted. Dimensions of LA, posterior wall box, pulmonary veins (PV) as well as LAA size and morphology were assessed and statistically analyzed. All important measures are depicted in the attached figure. Results From 2012 to 2016 a total of 1.103 patients underwent second generation cryoballoon PVI. Prior to PVI, CCTA was available for 725 (65.7%) patients with sufficient quality for measuring in 473 (65.2%). Mean age was 66.3±9.5 years; PAF was present in 277 (58.6%) participants. In persAF LA volume [mL] (111.8; 128.8; p<0.001), posterior wall box area [cm2] (11.9; 13.3; p<0.001) and pulmonary vein ostial dimensions were significantly larger compared to PAF. LAA volume [mL] (9.0; 10.0; p=0.01) and LAA ostial perimeters (66.5; 70.0; p=0.003) were also identified to be larger in persAF. However, there was no difference in LAA morphology (overall distribution: "windsock" 51%; "chicken-wing" 20%; "cauliflower" 15% and "cactus" 13%). Conclusion Compared to PAF, persAF patients had significantly larger LA volumes, posterior wall box areas, PV ostial dimensions as well as LAA volumes and LAA ostial perimeters. LAA morphological types were distributed equally in both groups.
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