Severe hypokalaemia can aggravate arrhythmia tendency and prognosis, but less is known about risk of mild hypokalaemia, which is a frequent finding. We examined the associations between mild hypokalaemia and ambulatory cardiac arrhythmias and their prognosis.
Subjects from the cohort of the 'Copenhagen Holter Study' (n = 671), with no history of manifest cardiovascular (CV) disease or stroke, were studied. All had laboratory tests and 48-h ambulatory electrocardiogram (ECG) recording. The median follow-up was 6.3 years. p-Potassium was inversely associated with frequency of premature ventricular complexes (PVCs) especially in combination with diuretic treatment (r = -0.22, P = 0.015). Hypokalaemia was not associated with supraventricular arrhythmias. Subjects at lowest quintile of p-potassium (mean 3.42, range 2.7-3.6 mmol/L) were defined as hypokalaemic. Cardiovascular mortality was higher in the hypokalaemic group (hazard ratio and 95% confidence intervals: 2.62 (1.11-6.18) after relevant adjustments). Hypokalaemia in combination with excessive PVC worsened the prognosis synergistically; event rates: 83 per 1000 patient-year in subjects with both abnormalities, 10 and 15 per 1000 patient-year in those with one abnormality, and 3 per 1000 patient-year in subjects with no abnormality. One variable combining hypokalaemia with excessive supraventricular arrhythmias gave similar results in univariate analysis, but not after multivariate adjustments.
In middle-aged and elderly subjects with no manifest heart disease, mild hypokalaemia is associated with increased rate of ventricular but not supraventricular arrhythmias. Hypokalaemia interacts synergistically with increased ventricular ectopy to increase the risk of adverse events.
The Danish National Research Foundation Centre for Cardiac Arrhythmia (DARC), Copenhagen, Denmark; Laboratory of Molecular Cardiology, Department of Cardiology, The Heart Centre, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark. Electronic address: email@example.com.
In this study, we investigated medical history and symptoms before death in all subjects aged 1 to 35 years who died a sudden cardiac death (SCD) from arrhythmogenic right ventricular cardiomyopathy (ARVC) in Denmark in the years 2000 to 2006. All deaths (n=6,629) in subjects aged 1 to 35 years in Denmark in the period 2000 to 2006 were included. A total of 16 cases of SCD due to ARVC were identified based on histopathologic examination. Information on medical history was retrieved from The National Patient Registry, general practitioners, and hospitals. Symptoms before death were compared with 2 control groups in the same age group and time interval: one consisting of subjects who died in traffic accidents (n=74) and the other consisting of patients who died a SCD due to coronary artery disease (CAD; n=34). In the case group, 8 of the 16 patients with ARVC experienced antecedent cardiac symptoms and 7 of them sought medical attention. None were diagnosed with ARVC before death. Only 1 patient in the healthy control group and 31 of the 39 patients with CAD experienced cardiac symptoms before death. A total of 6 patients of the 16 with ARVC died during strenuous physical activity and 4 of the deaths were sports-related SCDs. In conclusion, antecedent cardiac symptoms before SCD in the young were seen in 1/2 of the patients who died because of ARVC, and this is significantly higher than in the healthy control group. When considering the ARVC and CAD groups collectively, antecedent cardiac symptoms are seen in the majority.
Sudden infant death syndrome (SIDS) is the most common cause of death in infants between the age of 1 month and 1 year. Rare variants in Nav1.5 encoded by SCN5A are known to play a role in SIDS; however, the combined role of the sodium current complex is unknown.
The purpose of this study was to investigate the role of the sodium current complex in a nonreferred nationwide cohort of SIDS cases.
DNA was extracted from dried blood spot samples from the Danish Neonatal Screening Biobank. In total, 66 non-referred SIDS cases born in Denmark in the period of 2000-2006 were screened for genetic variants in the 8 major genes involved in the regulation of the Nav1.5 channel complex: SCN5A, SCN1B, SCN2B, SCN3B, SCN4B, GPD1L, SNTA1, and CAV3. Patch-clamp analyses were performed on variants not previously characterized.
In total, 8 patients (12%) had nonsynonymous rare variants in the sodium current genes. SCN5A harbored 6 rare variants (R458C, R535*, S1103Y, R1193Q, S1609L, and Q1909R); CAV3, 1 rare variant (T78M); GPD1L, 1 rare variant (R220H); and SCN3B, 1 rare variant (L10P). Four variants were considered likely pathogenic and 5 variants of unknown significance. SCN5A R1193Q and GPD1L R220H (both considered variants of unknown significance) were present in the same infant. Functional analysis of variants not previously characterized (R458C, S1609L, and Q1909R in SCN5A) predominantly revealed increased transient and sustained sodium current.
In a nonreferred nationwide Danish cohort of SIDS cases, up to 5/66 (7.5%) of SIDS cases can be explained by genetic variants in the sodium channel complex genes.
Hitherto, sudden cardiac death in children (SCDc)-defined as sudden cardiac death (SCD) in the 1-18 years old-has been incompletely described in the general population. Knowledge on incidence rates, causes of death and symptoms prior to death is sparse and has been affected by reporting and referral bias.
In a nationwide setting all deaths in children aged 1-18 years in Denmark in 2000-06 were included. To chart causes of death and incidence rates, death certificates and autopsy reports were collected and read. By additional use of the extensive healthcare registries in Denmark, we were also able to investigate prior disease and symptoms. During the 7-year study period there was an average of 1.11 million persons aged 1-18 years. There were a total of 1504 deaths (214 deaths per year) from 7.78 million person-years. A total of 114 (7.5%) were sudden and unexpected. A cardiac disease was known prior to death in 18% of all sudden unexpected death cases. In two-thirds of all sudden unexpected death cases no previous medical history was registered. Causes of death in autopsied cases were cardiac or unknown in 70%. Unexplained deaths, presumed to be a primary cardiac arrhythmia, accounted for 28% of autopsied sudden unexpected death cases. Autopsy rate was 77%. There were a total of 87 cases of SCDc (5.8% of all deaths). Prodromal symptoms were noted in 26% and antecedent symptoms in 45% of SCDc cases. The most frequent antecedent symptoms were seizures, dyspnoea, and syncope. In total, 61% of SCDc were not known with any prior disease; 23% were known with congenital or other heart disease prior to death. In total, 43 (49%) of all sudden unexpected deaths died of a potential inherited cardiac disease. The incidence rate of sudden unexpected death was 1.5 per 100 000 person-years. The highest possible incidence rate of SCDc was 1.1 per 100 000 person-years.
From a nationwide study of all deaths in a 7-year period more than half of all victims of SCDc experienced antecedent and/or prodromal symptoms prior to death. The incidence rate of sudden death and SCDc was 1.5 and 1.1 per 100 000 person-years, respectively. Cardiac symptoms in young persons should warrant clinical work-up and an autopsy should be performed in all cases of sudden unexpected death in which the deceased was not known with congenital heart disease prior to death. This is pivotal, in the subsequent familial cascade screening, to diagnose and treat potential inherited cardiac diseases in family members.