Severe hypokalemia secondary to abuse of ß-adrenergic agonists in a pediatric patient: Case report / Hipocalemia grave secundária a abuso de agonistas ß-adrenérgicos em paciente pediátrico: relato de caso

ABSTRACT This study reports a case of a 13-year-old male with a 3-year history of severe and intermittent hypokalemia episodes of unknown origin, requiring admission to the intensive care unit (ICU) for long QT syndrome (LQTS), finally diagnosed of redistributive hypokalemia secondary to the abuse of β-adrenergic agonists in the context of a probable factitious disorder.

RESUMO O presente estudo relata o caso de um jovem de 13 anos de idade com histórico, há três anos, de episódios de hipocalemia grave intermitente de origem desconhecida, internado em unidade de terapia intensiva (UTI) por síndrome do QT longo (SQTL). O paciente foi diagnosticado com hipocalemia por redistribuição secundária ao abuso de agonistas β-adrenérgicos, em contexto de provável transtorno factício.

Understanding the personal and community impact of long QT syndrome: A perspective from Gitxsan women.

There is a disproportionately high rate of hereditary long QT syndrome (LQTS) in Northern British Columbia First Nations people, largely due to a novel missense variant in KCNQ1 (p.V205M). The variant has been previously described predisposing those affected to syncope, arrhythmia, and sudden death. Although the biological aspects of LQTS have been explored extensively, less research has been done into the impact of living with a genetic variant that predisposes one to sudden death, and no previous studies have provided cultural insights from a First Nations community. The goal of this study was to explore what facilitates and hinders resiliency and coping for those living with LQTS. Participants were invited to partake in their choice of one-to-one interviews, Photovoice, and Talking Circles. This paper presents the findings from the interview portion of the study. Interviews were recorded, transcribed, and analyzed qualitatively using the systematic text condensation method. Ten women shared their personal experiences of living with LQTS through individual interviews. Half of the women had tested positive for the p.V205M variant, and the other half were awaiting results. In general, learning about a LQTS diagnosis was perceived as traumatic, with gradual acceptance that led to coping. The main factors found to facilitate resiliency and coping were positive family relationships, spirituality, and knowledge about LQTS. The main factors found to hinder resiliency and coping were a poor understanding of the biological or clinical aspects of LQTS, conflicting medical advice (especially regarding physical activity) and LQTS not being taken seriously by social contacts and healthcare providers. It appears that learning to live with LQTS is an ongoing process, requiring balance and interconnectedness between all aspects of well-being.

Type 1 long QT syndrome and psychological stress in a laboratory setting.

Trait-like sensitivity to stress in long QT syndrome patients has been documented previously. In addition, mental stress has been associated with symptomatic status of long QT syndrome. We examined whether the symptomatic type 1 long QT syndrome patients would be more sensitive to mental stress compared to asymptomatic patients and whether there would be differences in task-related physiological stress reactions between type 1 long QT syndrome patients and healthy individuals. The study population consisted of 21 symptomatic and 23 asymptomatic molecularly defined KCNQ1 mutation carriers, their 32 non-carrier relatives and 46 non-related healthy controls, with mean ages of 37, 39, 35 and 23 years, respectively. Electrocardiography was utilised to calculate inter-beat interval and high frequency and low frequency heart rate variability. Blood pressure was measured and mean arterial pressure and pulse pressure were calculated. Stress was induced using three different tasks: mental arithmetic, reaction time and public speech. Stress responses of symptomatic and asymptomatic type 1 long QT syndrome patients were not statistically different in any of the stress tasks. Short-term physiological stress reactivity of symptomatic type 1 long QT syndrome patients appears to be normal and does not enhance the risk assessment of asymptomatic mutation carriers.

QTc Prolongation in Patients with Dementia and Mild Cognitive Impairment: Neuropsychological and Brain Imaging Correlations.

The QTc interval is the electrocardiographic manifestation of ventricular depolarization and repolarization. This marker is often prolonged in acute and chronic neurological conditions. The cause of the cerebrogenic QT prolongation remains unclear. The aim of the study was to analyze the relation between QTc interval and the degree of cognitive impairment and structural brain imaging changes in patients with dementia and mild cognitive impairment (MCI). To this aim, 269 patients were screened, of whom 61 met one or more exclusion criteria. The remaining 208 patients (56 control subjects, 44 patients with MCI, and 108 with dementia) were recruited. Eighty-five patients using drugs causing prolongation of QT interval were further excluded. The QT interval was measured manually in all 12 leads by a single blinded observer, assuming the longest QT value adjusted for heart rate by using the Bazett's formula. All patients underwent a structural brain imaging and the following measures were obtained: the bicaudate ratio and the periventricular hyperintensity and deep white matter hyperintensity using the modified Fazekas scale. Prolonged QTc interval was prevalent in 1) patients with dementia, especially in those with moderate-severe degree; 2) subjects with impairment of praxis and attention, low functional status, and behavioral symptoms; 3) patients with global and temporal atrophy and with higher scores on the Fazekas or leukoaraiosis scales. Degenerative and vascular processes might play a main role in QTc interval prolongation because of the damage to brain areas involved in the control of the autonomic cardiac nervous system.

Reference frame and emotions may contribute to discrepancies in patient and clinician risk estimates in Long QT syndrome.

OBJECTIVE: Patients and clinicians need to have similar understandings of cardiac risk, so patients can make informed decisions. The aim of this study was to assess the concordance of risk estimates between Long-QT-Syndrome (LQTS) patients and an experienced clinician. METHODS: This cross-sectional study included 86 LQTS patients recruited from a clinical registry. Participants completed two questions on their risk of cardiac arrest; likelihood (1=very-unlikely to 5=very-likely), and chance (%), and an experienced clinician computed the same based on risk factors. RESULTS: 30% and 55% of patients had concordant perceptions with the clinician estimate on the chance and likelihood questions respectively. The patients who overestimated their risk (%) had significantly greater emotional responses and concerns about their LQTS. 22 (29%) patients reported a risk of 50% or greater, in contrast to the clinician's risk estimates not exceeding 30%. CONCLUSION: Many LQTS patients had discordant risk perceptions to the clinician's. Patients and clinicians may have different frames of reference, and patients' estimates are linked with emotions. PRACTICAL IMPLICATIONS: Clinicians need to take into account LQTS patients' different frame of reference when discussing risk information. This will support shared decision making.

Allowing Adolescents to Weigh Benefits and Burdens of High-stakes Therapies.

We present the case of a girl aged 17 years and 10 months who has a strong family history of long QT syndrome and genetic testing confirming the diagnosis of long QT syndrome in the patient also. She was initially medically treated with ß-blocker therapy; however, after suffering 1 episode of syncope during exertion, she underwent placement of an implantable cardioverter defibrillator. Since then, she has never had syncope. However, during the few months before this presentation, she experienced shocks on multiple occasions without any underlying arrhythmias. These shocks are disconcerting for her, and she is having significant anxiety about them. She requests the defibrillator to be inactivated. However, her mother, who also shares the diagnosis of long QT syndrome, disagrees and wants the defibrillator to remain active. The ethics team is consulted in this setting of disagreement between an adolescent, who is 2 months shy of the age of maturity and medical decision-making, and her mother, who is currently responsible for her medical decisions. The question for the consultation is whether it would be ethically permissible for the doctors to comply with the patient's request to turn off the defibrillator or whether the doctors should follow the mother's wishes until the patient is 18 years of age.

Severe hypokalemia secondary to abuse of ß-adrenergic agonists in a pediatric patient: Case report.

This study reports a case of a 13-year-old male with a 3-year history of severe and intermittent hypokalemia episodes of unknown origin, requiring admission to the intensive care unit (ICU) for long QT syndrome (LQTS), finally diagnosed of redistributive hypokalemia secondary to the abuse of ß-adrenergic agonists in the context of a probable factitious disorder.

The Genetic Counselor in the Pediatric Arrhythmia Clinic: Review and Assessment of Services.

There are minimal data on the impact of genetic counselors in subspecialty clinics, including the pediatric arrhythmia clinic. This study aimed to describe the clinical encounters of a genetic counselor integrated into a pediatric arrhythmia clinic. In the 20 months between July 2015 and February 2017, a total of 1914 scheduled patients were screened for indications relevant for assessment by a genetic counselor. Of these, the genetic counselor completed 276 patient encounters, seeing 14.4% of all patients in clinic. The most expected and common indications for genetic counselor involvement were related to suspicion for primary heritable arrhythmia conditions, though patients seen in this clinic display a wide range of cardiac problems and many additional indications for genetic evaluation were identified. Roughly 75% (211/276) of encounters were for personal history of confirmed/suspected heritable disease, including cardiac channelopathies, cardiomyopathies, ventricular arrhythmias, and congenital heart defects, and 25% (65/276) were for family history of disease, including long QT syndrome and sudden unexplained death. Overall, this study shows that about 1 in 7 patients seen in a pediatric arrhythmia clinic have indications that likely benefit from genetic counselor involvement and care. Similar service delivery models embedding genetic counselors in pediatric arrhythmia clinics should be encouraged, and this model could be emulated to increase patient access to genetic counseling services.

Evaluation of the Effects of Quetiapine on QTc Prolongation in Critically Ill Patients.

Quetiapine, an atypical antipsychotic used in the intensive care unit (ICU) to manage delirium, has a possible adverse effect of corrected QT (QTc) interval prolongation. The objective of this analysis was to describe the impact of quetiapine on QTc interval prolongation in critically ill patients. This was a single-center, prospective cohort analysis of ICU patients who received quetiapine between October 2015 and February 2016. The major end point was the incidence of QTc prolongation greater than 60 milliseconds above baseline during therapy. Minor end points included median change in QTc interval and incidence of Torsades de Pointes (TdP). Univariate and multivariable analyses were performed to determine variables associated with higher risk of QTc prolongation. During the study period, 103 patients were enrolled in the analysis. QTc interval prolongation greater than 60 milliseconds occurred in 14 (13.6%) patients. The median change in QTc interval was 20 milliseconds. There were no cases of TdP. On multivariable analysis, the only variable associated with higher incidence of QTc prolongation was administration of a concomitant medication known to prolong the QTc interval ( P = .046). QTc prolongation was relatively uncommon among critically ill patients utilizing quetiapine. Patients receiving concomitant medications known to prolong the QTc interval may be at an increased risk.

Quality of Life of Pediatric Patients With Long QT Syndrome.

Children with long QT syndrome (LQTS) live with the risk of sudden death, activity restrictions, and the need for daily medications. We sought to evaluate the quality of life (QOL), self-perception, and behavior of patients with LQTS as perceived by both patients and their parents and identify predictors of lower QOL. QOL (Pediatric QOL Inventory [PedsQL] and Pediatric Cardiac Quality of Life Inventory [PCQLI]), self-perception, and behavioral inventories were completed by patients with LQTS and their parents. Comparison of PedsQL scores was made to published data for healthy children using t tests, and PCQLI scores were compared with those of patients with differing complexity of congenital heart disease. Mixed modeling was used for multivariable analysis. Sixty-one patients with LQTS were evaluated (age 13.6 ± 3.0 years; male 49%). Compared with healthy children, the PedsQL Total, Psychosocial, and Physical Health Summary scores were significantly lower for patients with LQTS and parent proxy reports (p ≤0.001). In general, PCQLI scores of patients with LQTS and parents were similar to those of patients with tetralogy of Fallot (p ≥0.2), lower than those of patients with bicuspid aortic valve (p ≤0.02), and higher than those of patients with single ventricle (p ≤0.03). Lower patient and parent PCQLI scores were associated with internalizing problems. For parents, the presence of a cardiac device and medication side effects were additionally associated with lower PCQLI scores. In conclusion, patients with LQTS and their parents report lower QOL than normal children secondary to physical and psychosocial factors. Increasing focus on the psychological well-being of these patients is needed in an effort to improve their QOL.

Factors influencing uptake of familial long QT syndrome genetic testing.

Ongoing challenges of clinical assessment of long QT syndrome (LQTS) highlight the importance of genetic testing in the diagnosis of asymptomatic at-risk family members. Effective access, uptake, and communication of genetic testing are critical for comprehensive cascade family screening and prevention of disease complications such as sudden cardiac death. The aim of this study was to describe factors influencing uptake of LQTS genetic testing, including those relating to access and family communication. We show those who access genetic testing are overrepresented by the socioeconomically advantaged, and that although overall family communication is good, there are some important barriers to be addressed. There were 75 participants (aged 18 years or more, with a clinical and/or genetic diagnosis of LQTS; response rate 71%) who completed a survey including a number of validated scales; demographics; and questions about access, uptake, and communication. Mean age of participants was 46 ± 16 years, 20 (27%) were males and 60 (80%) had genetic testing with a causative gene mutation in 42 (70%). Overall uptake of cascade testing within families was 60% after 4 years from proband genetic diagnosis. All participants reported at least one first-degree relative had been informed of their risk, whereas six (10%) reported at least one first-degree relative had not been informed. Those who were anxious or depressed were more likely to perceive barriers to communicating. Genetic testing is a key aspect of care in LQTS families and intervention strategies that aim to improve equity in access and facilitate effective family communication are needed.

Depression requiring anti-depressant drug therapy in adult congenital heart disease: prevalence, risk factors, and prognostic value.

BACKGROUND: Depression is prevalent in adults with congenital heart disease (ACHD), but limited data on the frequency of anti-depressant drug (ADD) therapy and its impact on outcome are available. METHODS AND RESULTS: We identified all ACHD patients treated with ADDs between 2000 and 2011 at our centre. Of 6162 patients under follow-up, 204 (3.3%) patients were on ADD therapy. The majority of patients were treated with selective serotonin-reuptake inhibitors (67.4%), while only 17.0% of patients received tricyclic anti-depressants. Twice as many female patients used ADDs compared with males (4.4 vs. 2.2%, P < 0.0001). The percentage of patients on ADDs increased with disease complexity (P < 0.0001) and patient age (P < 0.0001). Over a median follow-up of 11.1 years, 507 (8.2%) patients died. After propensity score matching, ADD use was found to be significantly associated with worse outcome in male ACHD patients [hazard ratio 1.44 (95% confidence interval 1.17-1.84)]. There was no evidence that this excess mortality was directly related to ADD therapy, QT-prolongation, or malignant arrhythmias. However, males taking ADDs were also more likely to miss scheduled follow-up appointments compared with untreated counterparts, while no such difference in clinic attendance was seen in females. CONCLUSIONS: The use of ADD therapy in ACHD relates to gender, age, and disease complexity. Although, twice as many female patients were on ADDs, it were their male counterparts, who were at increased mortality risk on therapy. Furthermore, males on ADDs had worse adherence to scheduled appointments suggesting the need for special medical attention and possibly psychosocial intervention for this group of patients.

Stressful life events and depressive symptoms among symptomatic long QT syndrome patients.

We examined whether long QT syndrome status moderates the association between stressful life events and depressive symptoms. Participants were 562 (n= 246 symptomatic) long QT syndrome mutation carriers. Depressive symptoms were measured with a modified version of the Beck's Depression Inventory. There was an interaction between long QT syndrome status and stressful life events on depressive symptoms. In the symptomatic long QT syndrome patients, stressful life events were associated with depressive symptoms (B= 0.24, p< 0.001). In the asymptomatic long QT syndrome mutation carriers, this association was 62.5 percent weaker (B= 0.09, p= 0.057). Compared to asymptomatic long QT syndrome mutation carriers, symptomatic long QT syndrome patients are more sensitive to the depressive effects of stressful life events.

A novel life-threatening mutation in long QT2 syndrome.

BACKGROUND AND AIM: The aim of the report was to present a novel mutation in KCNH2 in a family with life-threatening long QT syndrome. METHODS: A genetic study using the method of next generation sequencing was performed in a 47-year-old woman after several episodes of syncope and torsade de pointes after sudden stress, with familial history of sudden death in first-degree female relatives. The study was performed also in her three asymptomatic children. Prolongation of QTc and typical ECG pattern of long QT2 were seen in the index case and in her youngest son. RESULTS: Novel mutations (p.F617V) in exon 7 of KCNH2 were found in the index case and in her youngest son. CONCLUSIONS: A novel heterozygous missense mutation in exon 7 of KCNH2 gene, causing a protein change p.F617V, was found in a family with life-threatening arrhythmias in women and clinical outcome typical for long QT2 syndrome.

Brief report: Emotional distress and recent stressful life events in long QT syndrome mutation carriers.

To study emotional distress in symptomatic and asymptomatic long QT syndrome mutation carriers who had experienced a recent stressful life event. The participants were 209 symptomatic and 279 asymptomatic long QT syndrome mutation carriers. Emotional distress was assessed with the Cope questionnaire and stressful life events with the Social Readjustment Rating Scale. Symptomatic long QT syndrome mutation carriers with burdening recent stressful life events reported a higher emotional distress (ß = 0.35, p < 0.001), while the asymptomatic did not show such difference (ß = 0.13, p = 0.393). Symptomatic long QT syndrome mutation carriers who have experienced stressful life events recently report an increased emotional distress.

Reduced Uptake of Family Screening in Genotype-Negative Versus Genotype-Positive Long QT Syndrome.

The acceptance and yield of family screening in genotype-negative long QT syndrome (LQTS) remains incompletely characterized. In this study of family screening for phenotype-definite Long QT Syndrome (LQTS, Schwartz score ≥3.5), probands at a regional Inherited Cardiac Arrhythmia clinic were reviewed. All LQTS patients were offered education by a qualified genetic counselor, along with materials for family screening including electronic and paper correspondence to provide to family members. Thirty-eight qualifying probands were identified and 20 of these had family members who participated in cascade screening. The acceptance of screening was found to be lower among families without a known pathogenic mutation (33 vs. 77 %, p = 0.02). A total of 52 relatives were screened; fewer relatives were screened per index case when the proband was genotype-negative (1.7 vs. 3.1, p = 0.02). The clinical yield of screening appeared to be similar irrespective of gene testing results (38 vs. 33 %, p = 0.69). Additional efforts to promote family screening among gene-negative long QT families may be warranted.

Cardiac anxiety after sudden cardiac arrest: Severity, predictors and clinical implications.

BACKGROUND: Survival from cardiac arrest is a medical success but simultaneously produces psychological challenges related to perception of safety and threat. The current study evaluated symptoms of cardiac-specific anxiety in sudden cardiac arrest (SCA) survivors and examined predictors of cardiac anxiety secondary to cardiac arrest. METHODS: A retrospective, cross-sectional study of 188 SCA survivors from the Sudden Cardiac Arrest Association patient registry completed an online questionnaire that included a measure of cardiac anxiety (CAQ) and sociodemographic, cardiac history, and psychosocial adjustment data. CAQ scores were compared to published means from implantable cardioverter defibrillator (ICD), inherited long QT syndrome (LQTS), and hypertrophic cardiomyopathy (HCM) samples and a hierarchical regression was performed. RESULTS: Clinically relevant cardiac anxiety and cardioprotective behaviors were frequently endorsed and 18% of survivors reported persistent worry about their heart even when presented with normal test results. Compared to all other samples, SCA survivors reported significantly higher levels of heart-focused attention (d=0.3-1.1) and greater cardiac fear and avoidance behaviors than LQTS patients. SCA patients endorsed less severe fear and avoidance symptoms than the HCM sample. Hierarchical regression analyses revealed that younger age (p=0.02), heart murmur (p=0.02), history of ICD shock≥1 (p=0.01), and generalized anxiety (p=0.008) significantly predicted cardiac anxiety. The overall model explained 29.2% of the total variance. CONCLUSIONS: SCA survivors endorse high levels of cardiac-specific fear, avoidance and preoccupation with cardiac symptoms. Successful management of SCA patients requires attention to anxiety about cardiac functioning and security.

Disclosing Genetic Information to Family Members About Inherited Cardiac Arrhythmias: An Obligation or a Choice?

Inherited cardiac arrhythmias such as long QT syndrome and Brugada syndrome, present clinical as well as ethical, legal, and social challenges. Many individuals who carry a deleterious mutation are largely asymptomatic and therefore may not be diagnosed until after the occurrence of a personal or family member's cardiac event. The familial nature of inherited genetic information raises numerous ethical, legal, and social issues regarding the sharing of genetic information, particularly when an individual found to carry a deleterious mutation refuses to disclose his or her results to at-risk family members who could benefit from life-saving treatments. This qualitative study sought to understand the experiences with genetic testing for individuals (n = 50) with a personal or family history of cardiac events or sudden death. Unstructured in-person focus groups or interviews were conducted for each participant in the study. The recordings of these interviews were transcribed verbatim and subsequently analyzed and coded. Participants' comments regarding sharing of genetic information centered around four main themes: (1) motivation to disclose; (2) extent of disclosure; (3) effect of disclosure on family dynamics; and (4) reasons for not sharing genetic information. The majority of individuals believed that affected individuals are obligated to disclose genetic information to family members. In the era of personalized medicine, the disclosure of genetic information provides individuals the opportunities to learn about the genetics, disease characteristics, and treatment options in order to reduce morbidity and mortality in themselves and their family members. Further research is necessary to identify and explore the barriers to sharing genetic information with at-risk family members.