Plasma Globotriaosylsphingosine Level as a Primary Screening Target for Fabry Disease in Patients With Left Ventricular Hypertrophy.

BACKGROUND: Although previous studies have suggested a certain prevalence of Fabry disease (FD) in left ventricular hypertrophy (LVH) patients, the screening of FD is difficult because of its wide-ranging clinical phenotypes. We aimed to clarify the utility of combined measurement of plasma globotriaosylsphingosine (lyso-Gb3) concentration and α-galactosidase A activity (α-GAL) as a primary screening of FD in unexplained LVH patients.Methods and Results:Between 2014 and 2016, both lyso-Gb3 and α-GAL were measured in 277 consecutive patients (male 215, female 62, age 25-79 years) with left ventricular wall thickness >12 mm on echocardiogram: 5 patients (1.8%) screened positive (2 (0.7%) showed high lyso-Gb3 and 4 (1.4%) had low α-GAL levels). Finally, 2 patients (0.7%) were diagnosed with clinically significant FD. In 1 case, a female heterozygote with normal α-GAL levels had genetic variants of unknown significance and was diagnosed as FD by endomyocardial biopsy. The other case was a male chronic renal failure patient requiring hemodialysis, and he had a p.R112H mutation. In both cases there were high lyso-Gb3 levels. CONCLUSIONS: The serum lyso-Gb3 level can be relevant for clinically significant FD, and combined measurement of lyso-Gb3 and α-GAL can provide better screening of FD in unexplained LVH patients.

Machine learning-based detection of sleep-disordered breathing in hypertrophic cardiomyopathy.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is often concomitant with sleep-disordered breathing (SDB), which can cause adverse cardiovascular events. Although an appropriate approach to SDB prevents cardiac remodelling, detection of concomitant SDB in patients with HCM remains suboptimal. Thus, we aimed to develop a machine learning-based discriminant model for SDB in HCM. METHODS: In the present multicentre study, we consecutively registered patients with HCM and performed nocturnal oximetry. The outcome was a high Oxygen Desaturation Index (ODI), defined as 3% ODI >10, which significantly correlated with the presence of moderate or severe SDB. We randomly divided the whole participants into a training set (80%) and a test set (20%). With data from the training set, we developed a random forest discriminant model for high ODI based on clinical parameters. We tested the ability of the discriminant model on the test set and compared it with a previous logistic regression model for distinguishing SDB in patients with HCM. RESULTS: Among 369 patients with HCM, 228 (61.8%) had high ODI. In the test set, the area under the receiver operating characteristic curve of the discriminant model was 0.86 (95% CI 0.77 to 0.94). The sensitivity was 0.91 (95% CI 0.79 to 0.98) and specificity was 0.68 (95% CI 0.48 to 0.84). When the test set was divided into low-probability and high-probability groups, the high-probability group had a higher prevalence of high ODI than the low-probability group (82.4% vs 17.4%, OR 20.9 (95% CI 5.3 to 105.8), Fisher's exact test p<0.001). The discriminant model significantly outperformed the previous logistic regression model (DeLong test p=0.03). CONCLUSIONS: Our study serves as the first to develop a machine learning-based discriminant model for the concomitance of SDB in patients with HCM. The discriminant model may facilitate cost-effective screening tests and treatments for SDB in the population with HCM.

Feasibility of Short-Term Aggressive Lipid-Lowering Therapy with the PCSK9 Antibody in Acute Coronary Syndrome.

BACKGROUND: The guideline-recommended low-density lipoprotein cholesterol target level of <70 mg/dL may not be achieved with statin administration in some patients with acute coronary syndrome (ACS). Therefore, the proprotein convertase subtilisin-kexin type 9 (PCSK9) antibody can be added to high-risk patients with ACS. Nevertheless, the optimal duration of PCSK9 antibody administration remains unclear. METHODS AND RESULTS: Patients were randomized to receive either 3 months of lipid lowering therapy (LLT) with the PCSK9 antibody followed by conventional LLT (with-PCSK9-antibody group) or 12 months of conventional LLT alone (without-PCSK9-antibody group). The primary endpoint was the composite of all-cause death, myocardial infarction, stroke, unstable angina, and ischemia-driven revascularization. A total of 124 patients treated with percutaneous coronary intervention (PCI) were randomly assigned to the two groups (n = 62 in each). The primary composite outcome occurred in 9.7% and 14.5% of the patients in the with- and without-PCSK9-antibody groups, respectively (hazard ratio: 0.70; 95% confidence interval: 0.25 to 1.97; p = 0.498). The two groups showed no significant differences in hospitalization for worsening heart failure and adverse events. CONCLUSIONS: In ACS patients who underwent PCI, short-term PCSK9 antibody therapy with conventional LLT was feasible in this pilot clinical trial. Long-term follow-up in a larger scale clinical trial is warranted.

Rapidly progressive myocardial calcification following sepsis.

Sepsis is a clinical syndrome caused by a dysregulated host response to infection that can lead to multiple organ dysfunction and death. Cardiovascular abnormalities are frequent in sepsis and may result in myocardial injury unrelated to coronary artery disease. Myocardial calcification is a rare complication of sepsis, which shows rapid-onset extensive myocardial calcifications. We present a case of a 67-year-old man who developed severe sepsis complicated with shock, acute renal failure, and acute respiratory distress syndrome. Initial chest computed tomography (CT) on admission showed normal left ventricular (LV) myocardial attenuation. However, serial chest CT demonstrated a gradual increase of the LV myocardial attenuation, which ultimately resulted in extensive myocardial calcification within 6 weeks. Sepsis-related myocardial calcification is usually found in patients with severe sepsis complicated with hemodynamic failure requiring vasopressors, acute renal failure necessitating renal replacement therapy, and acute respiratory distress syndrome. Although the prognostic significance of this pathology is unclear, it may be a precursor to long-term irreversible cardiomyopathy or an arrhythmogenic substrate that induces life-threatening arrhythmias. Therefore, patients who have survived the acute phase of severe sepsis need to be monitored carefully for signs of this complication by an imaging modality such as CT. .

Ethnic Identity Development and Acculturation: A Longitudinal Analysis of Mexican-Heritage Youth in the Southwest United States.

Utilizing part of the survey data collected for a National Institute on Drug Abuse (NIDA)-funded project from 29 public elementary schools in Phoenix, Arizona (N = 1,600), this study explored the underlying structure of Mexican-heritage youths' ethnic identity and cultural/linguistic orientation. Latent profile and transition analyses identified four distinct orientation profiles endorsed by the early adolescents and their developmental trends across four time points. Most Mexican and Mexican American adolescents endorsed bicultural profiles with developmental trends characterized by widespread stasis and transitions toward greater ethnic identity exploration. Multinominal logistic regression analyses revealed associations between profile endorsement and adolescents' gender, socioeconomic status, parents' birthplace, and visits outside the United States. These findings are discussed in regard to previous findings on acculturation and ethnic identity development. Individuals' adaptation to the immediate local environment is noted as a possible cause of prevalent biculturalism. Limitations and future directions for the research on ethnic identity development and acculturation are also discussed.

Unusual Serial Electrocardiographic Changes which Progressed to Arrhythmogenic Right Ventricular Cardiomyopathy.

Left ventricular (LV) involvement in the advanced stage of arrhythmogenic right ventricular cardiomyopathy (ARVC) is a well recognized phenomenon. T wave inversion in the lateral leads has been reported to be an electrocardiographic marker of LV involvement. Variants of ARVC that preferentially affect the left ventricle (left-dominant subtype of arrhythmogenic cardiomyopathy) have recently been recognized. We herein report a case in which an initial electrocardiogram that was similar to the left-dominant subtype of arrhythmogenic cardiomyopathy progressed to definitive ARVC over a period of 7 years. This case supports the hypothesis that LV involvement in ARVC may precede the evident onset of significant RV dysfunction.

Low WSS and High OSI Measured by 3D Cine PC MRI Reflect High Pulmonary Artery Pressures in Suspected Secondary Pulmonary Arterial Hypertension.

PURPOSE: Institutional Review Board (IRB)-approved prospective study was conducted to test whether objective and quantitative hemodynamic markers wall shear stress (WSS) and oscillatory shear index (OSI) measured by three-dimensional (3D) cine phase-contrast (PC) can reflect pulmonary arterial hypertension (PAH). PATIENTS AND METHODS: Seventeen consecutive patients of suspected secondary PAH were examined for pulmonary artery pressures (PAPs) with right heart catheterization (RHC) and three-dimensional (3D) cine PC MR. Based on the RHC data, patients were subdivided into two groups of 12 non-PAH (median age of 74.5 years) and 5 PAH (median age of 77 years) patients. Based on 3D cine PC magnetic resonance (MR), hemodynamic parameters including spatially averaged systolic WSS (sWSS), diastolic WSS (dWSS), mean WSS (mWSS), OSI and blood vessel section area (BVSA) at the pulmonary arterial trunk were calculated. Streamline images in the pulmonary arteries were also assessed. All the parameters were compared between non-PAH and PAH groups. RESULTS: sWSS (N/m(2)) and mWSS (N/m(2)) of PAH group was lower than that of non-PAH group (0.594 ± 0.067 vs. 0.961 ± 0.590, P = 0.001), (0.365 ± 0.035 vs. 0.489 ± 0.132, P = 0.027). OSI of PAH group was higher than that of non-PAH (0.214 ± 0.026 vs. 0.130 ± 0.046, P = 0.001). sWSS, mWSS, and dWSS were inversely correlated and OSI was positively correlated to mean PAP or systolic PAP with r values of -0.638 (P = 0.005), -0.643 (P = 0.005), -0.485 (P = 0.049), and 0.625 (P = 0.007); or -0.622 (P = 0.008), -0.629 (P = 0.007), -0.484 (P = 0.049), and 0.594 (P = 0.012), respectively. sWSS was also inversely correlated to BVSA with r value of -0.488 (P = 0.049), and OSI was correlated to BVSA with r value of 0.574 (P = 0.016). Vortex or helical flows were observed more frequently in PAH patients. CONCLUSIONS: The low sWSS and mWSS as well as high OSI measured with 3D cine PC MR could be potential hemodynamic markers for the increased PAP in suspected secondary PAH patients.