Andrew Aitken

Prospective, population-based long QT molecular autopsy study of postmortem negative sudden death in 1 to 40 year olds

BACKGROUND Retrospective investigation of sudden unexplained death in the young (SUDY) reveals that a high proportion is due to inherited heart disease. OBJECTIVE The purpose of this study was to ascertain the diagnostic value of postmortem long QT (LQT) genetic analysis in a prospective study of SUDY victims 1-40 years old. METHODS Denaturing high-performance liquid chromatography or direct sequencing of LQT genes 1, 2, 3, 5, and 6 was performed, in a National New Zealand protocol, in SUDY victims aged 1-40 years. RESULTS Over 26 months (2006-2008), DNA was stored at autopsy from 52 victims of sudden unexpected death. Further testing revealed a diagnosis in 19 cases (poisoning 4, dilated cardiomyopathy 3, myocarditis 3, other 9). The remaining 33 cases underwent genetic testing (age at death 18 months-40 years, median 25 years). Eighteen (55%) died during sleep or at rest, and 7 (21%) died during light activity. Rare missense variants in LQT genes were found in 5 (15%) cases (confidence interval 3%-27%): T96R in KCNQ1 (11-year-old male), P968L in KCNH2 (32-year-old female), P2006A in SCN5A (34-year-old female), and R67H and R98W in KCNE1 (17- and 38-year-old females, respectively). Evidence of pathogenicity was provided by in vitro evidence (T96R), family phenotype-genotype co-segregation (R98W, P2006A), and/or previous reports (R67H, P968L, P2006A, R98W). Family cardiac investigation was possible in 23 (70%) families and revealed probable cause of death for 5 (15%) other victims (confidence interval 3%-27%). CONCLUSION Most community SUDY occurs at rest or during light activity. A diagnostic rate of 15% supports the transition of LQT genetic autopsy, combined with family investigation, into routine medical practice.

Family acceptability of school-based echocardiographic screening for rheumatic heart disease in a high-risk population in New Zealand

Echocardiographic screening for rheumatic heart disease has been piloted in high‐risk areas in New Zealand and internationally, and fulfils most of the criteria for a targeted screening programme. The question of acceptability of rheumatic heart disease screening has not been assessed, and the aim of our study was to assess parental acceptability of a school‐based echocardiographic screening programme in a high‐risk population in New Zealand.

Inpatient detection of cardiac-inherited disease: the impact of improving family history taking

Objectives ‘Idiopathic’ cardiac conditions such as dilated cardiomyopathy (DCM) and resuscitated sudden cardiac death (RSCD) may be familial. We suspected that inpatient cardiology services fail to recognise this. Our objective was to compare diagnostic value of family histories recorded by inpatient cardiology teams with a multigenerational family tree obtained by specially trained allied professionals. Methods 2 experienced cardiology nurses working in 2 tertiary adult cardiac units were trained in cardiac-inherited diseases and family history (FHx) taking, and established as regional coordinators for a National Cardiac Inherited Disease Registry. Over 6 months they sought ‘idiopathic’ cardiology inpatients with conditions with a possible familial basis, reviewed the FHx in the clinical records and pursued a minimum 3-generation family tree for syncope, young sudden death and cardiac disease (full FHx). Results 37 patients (22 males) were selected: mean age 51 years (range 15–79). Admission presentations included (idiopathic) RSCD (14), dyspnoea or heart failure (11), ventricular tachycardia (2), other (10). 3 patients had already volunteered their familial diagnosis to the admitting team. FHx was incompletely elicited in 17 (46%) and absent in 20 (54%). 29 patients (78%) provided a full FHx to the coordinator; 12 of which (41%) were strongly consistent with a diagnosis of a cardiac-inherited disease (DCM 7, hypertrophic cardiomyopathy 3, long QT 1, left ventricular non-compaction 1). Overall, a familial diagnostic rate rose from 3/37(8%) to 12/37 (32%). Conclusions Adult cardiology inpatient teams are poor at recording FHx and need to be reminded of its powerful diagnostic value.