Classic electrocardiographic (ECG) voltage indexes have been applied to screen for left ventricular (LV) hypertrophy in hypertrophic cardiomyopathy (HC). However, it is unclear whether low ECG ...voltage reflects deteriorated electrical forces because of replacement of the myocardium by fibrotic tissues in HC. We investigated correlations between classic ECG voltage indexes (Cornell, total QRS voltage, and Sokolow-Lyon) and cardiac magnetic resonance (CMR) parameters focusing on the impact of low ECG voltage on the LV ejection fraction (LVEF) and myocardial fibrosis in HC. We studied 108 consecutive patients with HC who underwent CMR imaging with late gadolinium enhancement (LGE). Nineteen patients with complete right or left bundle branch block were excluded, leaving 89 patients for analysis (age 61.0 ± 13.9 years; 58 men). Of the 3 voltage indexes, the total QRS voltage and Sokolow-Lyon indexes were positively correlated with LVEF. For discriminating patients with end-stage HC (LVEF <50%) from patients with HC and preserved LVEF (≥50%), receiver-operating characteristic analysis revealed an excellent area under the curve of 0.87 for the total QRS voltage index and 0.90 for the Sokolow-Lyon index, whereas the area under the curve for the Cornell index was only 0.54 (p <0.01). Moreover, these 2 voltage indexes were negatively correlated with the extent of LGE-determined myocardial fibrosis when adjusted by the LV maximal wall thickness. In conclusion, low ECG voltage indexes may reflect increased myocardial fibrosis in patients with HC.
Sitosterolemia is a rare, inherited, autosomal recessive disorder of lipid metabolism characterized by increased levels of plant sterols, such as sitosterol and campesterol, xanthomas, and ...accelerated atherosclerosis. In a 15-year-old boy exhibiting ST-elevation acute myocardial infarction, lipid panels, including plant sterol, and genetic testing for the ATP-binding cassette sub-family G member 5 (ABCG5) gene mutation, confirmed the diagnosis of sitosterolemia. A comprehensive lipid panel and genetic testing should be considered in patients with premature coronary artery disease to prevent disease progression through dietary and pharmacologic interventions specific to sitosterolemia.
La sitostérolémie est une maladie génétique rare à transmission autosomique récessive touchant le métabolisme des lipides, qui est caractérisée par une augmentation des taux de stérols végétaux comme le sitostérol et le campestérol, la présence de xanthomes et une athérosclérose accélérée. Chez un garçon âgé de 15 ans ayant subi un infarctus aigu du myocarde avec élévation du segment ST, le diagnostic de sitostérolémie a été confirmé par un bilan lipidique comprenant un dosage des stérols d'origine végétale et un test génétique de dépistage de la mutation du gène ABCG5 (ATP-binding cassette sub-family G member 5). Un bilan lipidique exhaustif et un test génétique doivent être envisagés chez les patients présentant une coronaropathie prématurée afin de prévenir la progression de la maladie grâce à des interventions d'ordre tant diététique que pharmacologique propres à la sitostérolémie.
Abstract Background The development of candidate gene approaches to enable molecular diagnosis of hypertrophic cardiomyopathy (HCM) has required extensive and prolonged efforts. Whole exome ...sequencing (WES) technologies have already accelerated genetic studies of Mendelian disorders, yielding approximately 30% diagnostic success. As a result, there is great interest in extending the use of WES to any of Mendelian diseases. This study investigated the potential of WES for molecular diagnosis of HCM. Methods WES was performed on seven relatives from a large HCM family with a clear HCM phenotype (five clinically affected and two unaffected) in the Kanazawa University Hypertrophic Cardiomyopathy Registry. Serial bioinformatics filtering methods as well as using combined annotation dependent depletion (CADD) score and high heart expression (HHE) gene data were applied to detect the causative variant. Moreover, additional carriers of the variant were investigated in the HCM registry, and clinical characteristics harboring the variant were collected and evaluated. Results WES detected 60020 rare variants in the large HCM family. Of those, 3439 were missense, nonsense, splice-site, or frameshift variants. After genotype–phenotype matching, 13 putative variants remained. Using CADD score and HHE gene data, the number of candidates was reduced to one, a variant in the myosin essential light chain (MYL3, NM_000258.2:c.281G>A, p.Arg94His) that was shared by the five affected subjects. Additional screening of the HCM registry ( n = 600) identified two more subjects with this variant. Serial assessments of the variant carriers revealed the following phenotypic characteristics: (1) disease-penetrance of 88%; (2) all clinically affected carriers exhibited asymmetric septal hypertrophy with a substantial maximum left ventricular wall thickness of 18 ± 3 mm without any obstruction. Conclusions WES combined with CADD score and HHE gene data may be useful even in HCM. Furthermore, the MYL3 Arg94His variant was associated with high disease penetrance and substantial interventricular septal hypertrophy.
Abstract Background Population aging has rapidly progressed in Japan. However, few data exist regarding the characteristics of extremely elderly patients with out-of-hospital cardiac arrest (OHCA). ...We aimed to determine the prehospital predictors of one-month survival with favorable neurological outcomes (Cerebral Performance Category scale, category 1 or 2; CPC 1–2) in this population. Methods We investigated 23,520 OHCA patients aged ≥95 years from a prospectively recorded, nationwide, Utstein-style Japanese database between 2008 and 2012. The primary study endpoint was one-month CPC 1–2 after OHCA. Results The one-month CPC 1–2 rate was 0.27% (63/23,520). Only two variables were significantly associated with one-month CPC 1–2 in a multivariate logistic regression model: prehospital return of spontaneous circulation (ROSC) adjusted odds ratio (aOR), 94.4; 95% confidential interval (CI), 50.1–191.7 and emergency medical service (EMS)-witnessed arrest (aOR, 5.1; 95% CI, 2.6–10.2). When stratified by these two predictors, the one-month CPC 1–2 rates were 20.2% (18/89) for patients who had both prehospital ROSC and EMS-witnessed arrest, 4.2% (33/783) for those who had prehospital ROSC without EMS-witnessed arrest, 0.28% (3/1065) for those who had EMS-witnessed arrest without prehospital ROSC, and 0.04% (9/21,583) for those who had neither predictor, respectively. Conclusions The crucial prehospital predictors for one-month CPC 1–2 in elderly OHCA patients aged ≥95 years in Japan were prehospital ROSC and EMS-witnessed arrest and the former was the predominant predictor.
Abstract Objectives In this study, we scored patients with long QT syndrome (LQTS) according to the different Schwartz diagnostic criteria from 1993, 2006, and 2011, and to examine the validation of ...the criteria in relevance to the frequency of LQTS-related gene mutation. Background Although updated diagnostic criteria have been used in clinical settings, few data exist regarding their impact on the diagnosis of LQTS. Methods We used a cohort of 132 patients who presented with prolonged QTc intervals and/or abnormal clinical history in cardiac screening and who underwent exercise stress testing. LQTS scores of ≥3.5 points according to the 2006 and the 2011 criteria were considered to indicate a high probability of LQTS, as opposed to the 4 points used by the 1993 criteria. The 2011 criteria were updated by adding the evaluation of the recovery phase of exercise. Results The 2011 criteria significantly increased the number of high probability patients (n = 62) compared with the 1993 criteria (n = 32; p = 0.0002) or the 2006 criteria (n = 36; p = 0.0014). The percentage of mutation carriers in those with an intermediate score, which was rather high using the 1993 (53%) and 2006 criteria (53%), was greatly reduced with the 2011 criteria (15%, p = 0.0014 vs. the 1993 criteria, and p = 0.0013 vs. the 2006 criteria). Among 54 mutation carriers, the 1993, the 2006, and the 2011 criteria identified a high probability of carriers in 25 patients (46% sensitivity and 91% specificity), 27 patients (50% sensitivity and 88% specificity), and 48 patients (89% sensitivity and 82% specificity), respectively. Conclusions The use of the 2011 criteria will facilitate the diagnosis of LQTS and will decrease the number of false negative results.
Aggressive low-density lipoprotein (LDL) cholesterol-lowering therapy is important for high-risk patients. However, sparse data exist on the impact of combined aggressive LDL cholesterol-lowering ...therapy in familial hypercholesterolemia (FH), particularly on side effects to changes in plasma coenzyme Q10 and proprotein convertase subtilisin/kexin type 9 levels. We enrolled 17 Japanese patients with heterozygous FH (12 men, 63.9 ± 7.4 years old) with single LDL receptor gene mutations in a prospective open randomized study. Permitted maximum doses of rosuvastatin (20 mg/day), ezetimibe (10 mg/day), and granulated colestimide (3.62 g/day) were introduced sequentially. Serum levels of LDL cholesterol decreased significantly by −66.4% (p <0.001) and 44% of participants achieved LDL cholesterol levels <100 mg/dl. There were no serious side effects or abnormal laboratory data that would have required the protocol to have been terminated except for 1 patient with myalgia. Coadministration of ezetimibe and granulated colestimide further lowered serum LDL cholesterol more than rosuvastatin alone without changing plasma coenzyme Q10 and proprotein convertase subtilisin/kexin type 9 levels. In conclusion, adequate introduction of this aggressive cholesterol-lowering regimen can improve the lipid profile of FH.
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