Citations

Introduction: Current proposed Dietary Guidelines for Americans, 2015 suggested replacing refined grains (e.g., white rice) with whole grains (e.g., brown rice) for improved health outcomes; however, the association between white rice consumption and risk of cardiovascular disease (CVD) was not fully investigated. The purpose of this study was to explore the associations between rice consumption, metabolic syndrome and cardiovascular disease. Methods: We conducted a comprehensive search of MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, EMBASE, Scopus, and the Cochrane Central Register of Controlled Trials from database inception through May 2015. Observational studies were included if the studies reported hazard ratios (HRs) or odd ratios (ORs) of the associations between rice consumption, metabolic syndrome and cardiovascular disease. Data were extracted by one reviewer and then reviewed by two independent reviewers. Conflicts were resolved through consensus. Using the DerSimonian and Laird random effects models, we calculated pooled HRs and pooled ORs with 95% confidence intervals (95% CIs). Subgroup analyses were performed to explore potential sources of heterogeneity. The quality of the included studies and publication bias were assessed. Results: Out of 343 retrieved articles, we identified 6 cross-sectional and 9 prospective studies with a total of 575,852 individuals with 24,649 total CVD events and 4,409 metabolic syndrome cases. The highest category of white rice consumption (≥5 times/week) was associated with a 37% higher risk of metabolic syndrome (pooled OR, 1.37; 95% CI: 1.03-1.84; p<0.001; I 2 = 78.7%) but not a higher risk of cardiovascular disease (pooled HR, 1.01; 95% CI: 0.95-1.08; p=0.65; I 2 = 0%), compared to the lowest category (≤1 time/month). Conclusions: Higher white rice consumption has not been shown to increase the risk of cardiovascular diseases but may be associated with increased risk of metabolic syndrome.

Abstract Background Pathogenic variants in the lamin A/C gene (LMNA) can lead to a wide range of phenotypes from dilated and arrhythmogenic cardiomyopathies and conduction abnormalities to partial lipodystrophies. This case highlights a coincidental pathogenic LMNA variant identified in a patient with sudden cardiac arrest (SCA). We demonstrate the need for careful interpretation of pathogenic variants identified in cardiomyopathy genes by highlighting a case in which a coincidental pathogenic LMNA variant was found in a patient with premature ventricular complex (PVC)-induced ventricular fibrillation (VF). Case summary We present the case of a 16-year-old male with SCA secondary to VF. Genetic testing identified a maternally inherited pathogenic variant in LMNA annotated c.1961dup; p.T655Nfs*49. The patient received an implantable cardiac defibrillator and was discharged on nadolol. The patient’s two brothers were also variant-positive. However, the patient and both brothers had normal chamber dimensions on echocardiogram and no late gadolinium enhancement on cardiac magnetic resonance imaging. The family members with the variant were recommended to have prophylactic implantable cardiac defibrillators and thus sought a second opinion. The patient received an appropriate shock and device interrogation identified PVCs. Electrophysiology study identified PVC-induced VF which was ablated with no recurrent ventricular arrhythmias/implantable cardioverter defibrillator therapies over 8 months of follow-up. Although the variant in LMNA could lead to cardiac arrest, the clinical phenotype was consistent with a non-genetic aetiology. The family members were told to have periodic cardiac evaluation. Discussion This case demonstrates the identification of a coincidental pathogenic variant in a cardiomyopathy gene in a patient with cardiac arrest. Although this variant could lead to cardiomyopathy, it appears the cardiac arrest was not due to the pathogenic variant. This highlights the need to consider the clinical phenotype when interpreting genetic test results for cardiomyopathies even in the presence of a positive genetic test result.

Background: Sudden cardiac arrest (SCA) and sudden unexplained death (SUD) are feared sequelae of many genetic heart diseases. In rare circumstances, pathogenic variants in cardiomyopathy-susceptibility genes may result in electrical instability leading to SCA/SUD before any structural manifestations of underlying cardiomyopathy are evident. Methods: Collectively, 38 unexplained SCA survivors (21 males; mean age at SCA 26.4±13.1 years), 68 autopsy-inconclusive SUD cases (46 males; mean age at death 20.4±9.0 years) without disease-causative variants in the channelopathy genes, and 973 ostensibly healthy controls were included. Following exome sequencing, ultrarare (minor allele frequency ≤0.00005 in any ethnic group within Genome Aggregation Database [gnomAD, N=141 456 individuals]) nonsynonymous variants identified in 24 Clinical Genome Resource adjudicated definitive/strong evidence cardiomyopathy-susceptibility genes were analyzed. Eligible variants were adjudicated as pathogenic, likely pathogenic, or variant of uncertain significance in accordance with current American College of Medical Genetics and Genomics guidelines. Results: Overall, 7 out of 38 (18.4%) SCA survivors and 14 out of 68 (20.5%) autopsy-inconclusive, channelopathic-negative SUD cases had at least one pathogenic/likely pathogenic or a variant of uncertain significance nonsynonymous variant within a strong evidence, cardiomyopathy-susceptibility gene. Following American College of Medical Genetics and Genomics criterion variant adjudication, a pathogenic or likely pathogenic variant was identified in 3 out of 38 (7.9%; P =0.05) SCA survivors and 8 out of 68 (11.8%; P =0.0002) autopsy-inconclusive SUD cases compared to 20 out of 973 (2.1%) European controls. Interestingly, the yield of pathogenic/likely pathogenic variants was significantly greater in autopsy-inconclusive SUD cases with documented interstitial fibrosis (4/11, 36%) compared with only 4 out of 57 (7%, P <0.02) SUD cases without ventricular fibrosis. Conclusions: Our data further supports the inclusion of strong evidence cardiomyopathy-susceptibility genes on the genetic testing panels used to evaluate unexplained SCA survivors and autopsy-inconclusive/negative SUD decedents. However, to avoid diagnostic miscues, the careful interpretation of genetic test results in patients without overt phenotypes is vital.

Background: Symptomatic children with catecholaminergic polymorphic ventricular tachycardia (CPVT) are at risk for recurrent arrhythmic events. β-Blockers decrease this risk, but studies comparing individual β-blockers in sizeable cohorts are lacking. We aimed to assess the association between risk for arrhythmic events and type of β-blocker in a large cohort of symptomatic children with CPVT. Methods: From 2 international registries of patients with CPVT, RYR2 variant–carrying symptomatic children (defined as syncope or sudden cardiac arrest before β-blocker initiation and age at start of β-blocker therapy <18 years), treated with a β-blocker were included. Cox regression analyses with time-dependent covariates for β-blockers and potential confounders were used to assess the hazard ratio (HR). The primary outcome was the first occurrence of sudden cardiac death, sudden cardiac arrest, appropriate implantable cardioverter-defibrillator shock, or syncope. The secondary outcome was the first occurrence of any of the primary outcomes except syncope. Results: We included 329 patients (median age at diagnosis, 12 [interquartile range, 7–15] years, 35% females). Ninety-nine (30.1%) patients experienced the primary outcome and 74 (22.5%) experienced the secondary outcome during a median follow-up of 6.7 (interquartile range, 2.8–12.5) years. Two-hundred sixteen patients (66.0%) used a nonselective β-blocker (predominantly nadolol [n=140] or propranolol [n=70]) and 111 (33.7%) used a β1-selective β-blocker (predominantly atenolol [n=51], metoprolol [n=33], or bisoprolol [n=19]) as initial β-blocker. Baseline characteristics did not differ. The HRs for both the primary and secondary outcomes were higher for β1-selective compared with nonselective β-blockers (HR, 2.04 [95% CI, 1.31–3.17]; and HR, 1.99 [95% CI, 1.20–3.30], respectively). When assessed separately, the HR for the primary outcome was higher for atenolol (HR, 2.68 [95% CI, 1.44–4.99]), bisoprolol (HR, 3.24 [95% CI, 1.47–7.18]), and metoprolol (HR, 2.18 [95% CI, 1.08–4.40]) compared with nadolol, but did not differ from propranolol. The HR of the secondary outcome was only higher in atenolol compared with nadolol (HR, 2.68 [95% CI, 1.30–5.55]). Conclusions: β1-selective β-blockers were associated with a significantly higher risk for arrhythmic events in symptomatic children with CPVT compared with nonselective β-blockers, specifically nadolol. Nadolol, or propranolol if nadolol is unavailable, should be the preferred β-blocker for treating symptomatic children with CPVT.

Background Sudden cardiac arrest is the leading mode of death in the United States. Epilepsy affects 1% of Americans; yet epidemiological data show a prevalence of 4% in cases of sudden cardiac arrest. Sudden unexpected death in epilepsy (SUDEP) may share features with sudden cardiac arrest. The objective of this study was to report autopsy and genomic findings in a large cohort of SUDEP cases. Methods and Results Mayo Clinic Sudden Death Registry containing cases (ages 0–90 years) of sudden unexpected and unexplained deaths 1960 to present was queried. Exome sequencing performed on decedent cases. From 13 687 cases of sudden death, 656 (4.8%) had a history of seizures, including 368 confirmed by electroencephalography, 96 classified as SUDEP, 58 as non‐SUDEP, and 214 as unknown (insufficient records). Mean age of death in SUDEP was 37 (±19.7) years; 56 (58.3%) were male; 65% of deaths occurred at night; 54% were found in bed; and 80.6% were prone. Autopsies were obtained in 83 cases; bystander coronary artery disease was frequently reported as cause of death; nonspecific fibrosis was seen in 32.6% of cases, in structurally normal hearts. There were 4 cases of Dravet syndrome with pathogenic variants in SCN1A gene. Using whole exome sequencing in 11 cases, 18 ultrarare nonsynonymous variants were identified in 6 cases including CACNB2, RYR2, CLNB, CACNA1H, and CLCN2 . Conclusions This study examined one of the largest single‐center US series of SUDEP cases. Several cases were reclassified as SUDEP, 15% had an ECG when alive, and 11 (11.4%) had blood for whole exome sequencing analysis. The most frequent antemortem genetic finding was pathogenic variants in SCN1A ; postmortem whole exome sequencing identified 18 ultrarare variants.