Cardiac Mechanical Alterations and Genotype Specific Differences in Subjects With Long QT Syndrome

AbstractObjectivesThis study aimed to explore systolic and diastolic function and to investigate genotype-specific differences in subjects with long QT syndrome (LQTS).BackgroundLQTS is an arrhythmogenic cardiac ion channelopathy that traditionally has been considered a purely electrical disease. The most commonly affected ion channels are the slow potassium channel, IKs (KCNQ1 gene/LQT1), and the rapid potassium channel, IKr (KCNH2 gene/LQT2). Recent reports have indicated mechanical abnormalities in patients with LQTS.MethodsWe included 192 subjects with genotyped LQTS (139 LQT1, 53 LQT2). Healthy persons of similar age and sex as patients served as controls (n = 60). Using echocardiography, we assessed systolic function by left ventricular (LV) ejection fraction (EF), global longitudinal strain (GLS), and contraction duration (16 LV segments). Mechanical dispersion was calculated as standard deviation of contraction duration. Time difference between contraction duration and QT interval from electrocardiography (ECG) was defined as electromechanical time difference. We assessed diastolic function by transmitral filling velocities, early diastolic myocardial velocity (e′), and left atrial volume index (LAVI). Heart rate corrected QT interval (QTc) was assessed from 12-lead ECG.ResultsSystolic function by GLS was reduced in subjects with LQTS compared with healthy controls (−22.1 ± 2.1% vs. −23.0 ± 2.0%, p = 0.01), and GLS was worse in subjects with LQT2 compared with subjects with LQT1 (p = 0.01). Subjects with LQTS had longer contraction duration (426 ± 41 ms vs. 391 ± 36 ms, p < 0.001) and more dispersed contractions (33 ± 14 ms vs. 21 ± 7 ms, p < 0.001) compared with healthy controls. Diastolic function was also reduced in subjects with LQTS compared with healthy controls; e′ was lower (10.7 ± 2.7 cm/s vs. 12.5 ± 2.0 cm/s, p < 0.001), and LAVI was increased (30 ± 8 ml/m2 vs. 26 ± 5 ml/m2, p = 0.01), also when adjusted for age and other possible confounders.ConclusionsSubjects with LQTS had a consistent reduction in both systolic and diastolic function compared with healthy controls. Differences in myocardial function between subjects with LQT1 and subjects with LQT2 may indicate that mechanical alterations in LQTS are genotype specific

Treatment and outcomes of crisis resolution teams: a prospective multicentre study

<p>Abstract</p> <p>Background</p> <p>Crisis resolution teams (CRTs) aim to help patients in acute mental health crises without admitting them to hospital. The aims of this study were to investigate content of treatment, service practice, and outcomes of crises of CRTs in Norway.</p> <p>Methods</p> <p>The study had a multicentre prospective design, examining routine data for 680 patients and 62 staff members of eight CRTs. The clinical staff collected data on the demographic, clinical, and content of treatment variables. The service practices of the staff were assessed on the Community Program Practice Scale. Information on each CRT was recorded by the team leaders. The outcomes of crises were measured by the changes in Global Assessment of Functioning scale scores and the total scores on the Health of the Nation Outcome Scales between admission and discharge. Regression analysis was used to predict favourable outcomes.</p> <p>Results</p> <p>The mean length of treatment was 19 days for the total sample (N = 680) and 29 days for the 455 patients with more than one consultation; 7.4% of the patients had had more than twice-weekly consultations with any member of the clinical staff of the CRTs. A doctor or psychologist participated in 55.5% of the treatment episodes. The CRTs collaborated with other mental health services in 71.5% of cases and with families/networks in 51.5% of cases. The overall outcomes of the crises were positive, with a small to medium effect size. Patients with depression received the longest treatments and showed most improvement of crisis. Patients with psychotic symptoms and substance abuse problems received the shortest treatments, showed least improvement, and were most often referred to other parts of the mental health services. Length of treatment, being male and single, and a team focus on out-of-office contact were predictors of favourable outcomes of crises in the adjusted model.</p> <p>Conclusions</p> <p>Our study indicates that, compared with the UK, the Norwegian CRTs provided less intensive and less out-of-office care. The Norwegian CRTs worked more with depression and suicidal crises than with psychoses. To be an alternative to hospital admission, the Norwegian CRTs need to intensify their treatment and meet more patients outside the office.</p

The added value of abnormal regional myocardial function for risk prediction in arrhythmogenic right ventricular cardiomyopathy

Aims A risk calculator for individualized prediction of first-time sustained ventricular arrhythmia (VA) in arrhythmogenic right ventricular cardiomyopathy (ARVC) patients has recently been developed and validated (www.ARVCrisk.com). This study aimed to investigate whether regional functional abnormalities, measured by echocardiographic deformation imaging, can provide additional prognostic value. Methods From two referral centres, 150 consecutive patients with a definite ARVC diagnosis, no prior sustained VA, and an echo- and results cardiogram suitable for deformation analysis were included (aged 41 ± 17 years, 50% female). During a median follow-up of 6.3 (interquartile range 3.1–9.8) years, 37 (25%) experienced a first-time sustained VA. All tested left and right ventricular (LV and RV) deformation parameters were univariate predictors for first-time VA. While LV function did not add predictive value in multivariate analysis, two RV deformation parameters did; RV free wall longitudinal strain and regional RV deformation patterns remained independent predictors after adjusting for the calculator-predicted risk [hazard ratio 1.07 (95% CI 1.02–1.11); P = 0.004 and 4.45 (95% CI 1.07–18.57); P = 0.040, respectively] and improved its discriminative value (from C-statistic 0.78 to 0.82 in both; Akaike information criterion change > 2). Importantly, all patients who experienced VA within 5 years from the echocardiographic assessment had abnormal regional RV deformation patterns at baseline. Conclusions This study showed that regional functional abnormalities measured by echocardiographic deformation imaging can further refine personalized arrhythmic risk prediction when added to the ARVC risk calculator. The excellent negative predictive value of normal RV deformation could support clinicians considering the timing of implantable cardioverter defibrillator implantation in patients with intermediate arrhythmic risk

Implantable cardioverter defibrillator use in arrhythmogenic right ventricular cardiomyopathy in North America and Europe

Background and aims: Implantable cardioverter-defibrillators (ICDs) are critical for preventing sudden cardiac death (SCD) in arrhythmogenic right ventricular cardiomyopathy (ARVC). This study aims to identify cross-continental differences in utilization of primary prevention ICDs and survival free from sustained ventricular arrhythmia (VA) in ARVC. Methods: This was a retrospective analysis of ARVC patients without prior VA enrolled in clinical registries from 11 countries throughout Europe and North America. Patients were classified according to whether they received treatment in North America or Europe and were further stratified by baseline predicted VA risk into low- (25%/5 years) groups. Differences in ICD implantation and survival free from sustained VA events (including appropriate ICD therapy) were assessed. Results: One thousand ninety-eight patients were followed for a median of 5.1 years; 554 (50.5%) received a primary prevention ICD, and 286 (26.0%) experienced a first VA event. After adjusting for baseline risk factors, North Americans were more than three times as likely to receive ICDs {hazard ratio (HR) 3.1 [95% confidence interval (CI) 2.5, 3.8]} but had only mildly increased risk for incident sustained VA [HR 1.4 (95% CI 1.1, 1.8)]. North Americans without ICDs were at higher risk for incident sustained VA [HR 2.1 (95% CI 1.3, 3.4)] than Europeans. Conclusions: North American ARVC patients were substantially more likely than Europeans to receive primary prevention ICDs across all arrhythmic risk strata. A lower rate of ICD implantation in Europe was not associated with a higher rate of VA events in those without ICDs

An implementation study of the crisis resolution team model in Norway: Are the crisis resolution teams fulfilling their role?

Background The establishment of crisis resolution teams (CRTs) is part of the national mental health policy in several Western countries. The purpose of the present study is to describe characteristics of CRTs and their patients, explore the differences between CRTs, and examine whether the CRTs in Norway are organized according to the international CRT model. Methods The study was a naturalistic study of eight CRTs and 680 patients referred to these teams in Norway. Mental health problems were assessed using the Health of the Nation Outcome Scales (HoNOS), Global Assessment of Functioning Scales (GAF) and the International Statistical Classification of Diseases and Related Health Problems, 10th Revision (ICD-10). Results None of the CRTs operated 24 hours a day, seven days a week (24/7 availability) or had gate-keeping functions for acute wards. The CRTs also treated patients who were not considered for hospital admission. Forty per cent of patients waited more than 24 hours for treatment. Fourteen per cent had psychotic symptoms, and 69% had affective symptoms. There were significant variations between teams in patients' total severity of symptoms and social problems, but no variations between teams with respect to patients' aggressive behaviour, non-accidental self-injury, substance abuse or psychotic symptoms. There was a tendency for teams operating extended hours to treat patients with more severe mental illnesses. Conclusions The CRT model has been implemented in Norway without a rapid response, gate-keeping function and 24/7 availability. These findings indicate that the CRTs do not completely fulfil their intended role in the mental health system

Implantable cardioverter defibrillator use in arrhythmogenic right ventricular cardiomyopathy in North America and Europe

BACKGROUND AND AIMS: Implantable cardioverter-defibrillators (ICDs) are critical for preventing sudden cardiac death (SCD) in arrhythmogenic right ventricular cardiomyopathy (ARVC). This study aims to identify cross-continental differences in utilization of primary prevention ICDs and survival free from sustained ventricular arrhythmia (VA) in ARVC. METHODS: This was a retrospective analysis of ARVC patients without prior VA enrolled in clinical registries from 11 countries throughout Europe and North America. Patients were classified according to whether they received treatment in North America or Europe and were further stratified by baseline predicted VA risk into low- (25%/5 years) groups. Differences in ICD implantation and survival free from sustained VA events (including appropriate ICD therapy) were assessed. RESULTS: One thousand ninety-eight patients were followed for a median of 5.1 years; 554 (50.5%) received a primary prevention ICD, and 286 (26.0%) experienced a first VA event. After adjusting for baseline risk factors, North Americans were more than three times as likely to receive ICDs {hazard ratio (HR) 3.1 [95% confidence interval (CI) 2.5, 3.8]} but had only mildly increased risk for incident sustained VA [HR 1.4 (95% CI 1.1, 1.8)]. North Americans without ICDs were at higher risk for incident sustained VA [HR 2.1 (95% CI 1.3, 3.4)] than Europeans. CONCLUSIONS: North American ARVC patients were substantially more likely than Europeans to receive primary prevention ICDs across all arrhythmic risk strata. A lower rate of ICD implantation in Europe was not associated with a higher rate of VA events in those without ICDs

Mother-to-child transmission of HIV : When a child inherits HIV from its mother

The thesis comprises a literature review, a histopathology study of placentas from Kenya in addition to observations and reflections from a field study in primary health care clinics in Moshi, Tanzania. Transmission of HIV from a HIV-positive woman to her unborn child or infant is defined as Mother-To-Child-Transmission, MTCT. The virus can be transmitted during pregnancy, delivery or after birth through breast milk. Ante partum transmission can take place blood borne through placenta or ascending from cervico-vaginal secretions. Morphologically the placentas of HIV-positives show higher incidence of chorioamnionitis. There are no placental changes known as specific HIV-features. Three interventions are proven efficient in reducing the MTCT. They are antiretroviral therapy to the woman before and during delivery and to the newborn, caesarean section and avoiding breastfeeding, alternatively exclusive breastfeeding. In industrialized countries these interventions have reduced the MTCT-rate from up to 45% to less than 2%. WHO estimate that more than 40 million people currently live with HIV/AIDS. 25-28 million of these live in Sub-Saharan Africa, including over 2 million infected in Tanzania. Several years with HIV focus by the Tanzanian government and increasing international and private support have resulted in programs for fighting the HIV epidemic, including national pilot programs against MTCT. In June/July 2003 I worked in an ongoing local MTCT pilot program in health clinics in Moshi, a small town close to Kilimanjaro. I observed HIV s role and influence in an African community and how health personnel handled the problem with limited resources. Despite international engagement, improved financing and focus on HIV, the HIV-fighting programs in developing countries have not showed the expected results. HIV is still spreading and the situation is far from being under control. Efficient use of financial resources is threatened by capacity shortfalls in health service systems at district level, lack of health- and administrative personnel as well as dysfunctional infrastructure. An even larger problem is low compliance in populations to use services being offered in HIV-programs. Lack of knowledge and delusions influenced by local culture, religion and witchcraft have been identified. Stigma however, is the most important obstacle to compliance. HIV is still associated with personal guilt and shame. HIV-positives are maltreated and discriminated in their local community. People thus often choose not to tell they are infected. They don t use preventive methods as condoms and they breastfeed their children to avoid rumours in the community. People additionally consider HIV-infection as a death sentence no point knowing. Primary prevention to avoid HIV-infection must be the global number one goal, also in the work against MTCT. In order to succeed in HIV-combat programs it is also important to eradicate stigma, demystify HIV/AIDS, focus on human rights and support the HIV-infected to give them hope for a decent future