Nina E. Hasselberg

Vigorous physical activity impairs myocardial function in patients with arrhythmogenic right ventricular cardiomyopathy and in mutation positive family members

Exercise increases risk of ventricular arrhythmia in subjects with arrhythmogenic right ventricular cardiomyopathy (ARVC). We aimed to investigate the impact of exercise on myocardial function in ARVC subjects.

Left ventricular global longitudinal strain is associated with exercise capacity in failing hearts with preserved and reduced ejection fraction

Aims Heart failure patients with reduced and preserved left ventricular (LV) ejection fraction (EF) show reduced exercise capacity. We explored the relationship between exercise capacity and systolic and diastolic myocardial function in heart failure patients. Methods and results Exercise capacity, by peak oxygen uptake (VO2), was assessed in 100 patients (56 ± 12 years, NYHA functional class: 2.5 ± 0.9, EF: 42 ± 19%). LV systolic function, as EF and global longitudinal strain (GLS), and right ventricular function were assessed by echocardiography. Left atrial volume index and the ratio of peak early diastolic filling velocity (E) to early diastolic mitral annular velocity (e′) were measures of diastolic function. Thirty-seven patients had heart failure with preserved EF (HFpEF), defined as EF ≥50% and echocardiographic diastolic dysfunction. LV GLS and peak pulmonary arterial systolic pressure were independently correlated to peak VO2 in the total study population and in HFpEF separately. LV GLS was superior to EF in identifying patients with impaired peak VO2 <20 mL/kg/min as shown by receiver operating characteristic analyses [areas under curves 0.93 (0.89–0.98) vs. 0.85 (0.77–0.93), P < 0.05]. In patients with HFpEF, GLS was reduced below normal (−17.5 ± 3.2%) and correlated to E/e′ (R = 0.45, P = 0.005) and left atrial volume index (R = 0.48, P = 0.003), while EF did not. Conclusion GLS correlated independently to peak VO2 in patients with reduced and preserved EF and was superior in identifying patients with reduced exercise capacity. In HFpEF, systolic function by GLS was impaired. There was a significant relationship between diastolic function and GLS, confirming a coupling between diastolic and longitudinal systolic function in HFpEF.

Strain echocardiography is related to fibrosis and ventricular arrhythmias in hypertrophic cardiomyopathy

Aims Hypertrophic cardiomyopathy (HCM) patients are at risk of ventricular arrhythmias (VAs). We aimed to explore whether systolic function by strain echocardiography is related to VAs and to the extent of fibrosis by cardiac magnetic resonance imaging (CMR). Methods and results We included 150 HCM patients and 50 healthy individuals. VAs were defined as non-sustained and sustained ventricular tachycardia and aborted cardiac arrest. Left ventricular function was assessed by ejection fraction (EF) and by global longitudinal strain (GLS) assessed by speckle tracking echocardiography. Mechanical dispersion was calculated as standard deviation (SD) of time from Q/R on ECG to peak longitudinal strain in 16 left ventricular segments. Late gadolinium enhancement (LGE) was assessed by CMR. HCM patients had similar EF (61 ± 5% vs. 61 ± 8%, P = 0.77), but worse GLS (−15.7 ± 3.6% vs. −21.1 ± 1.9%, P < 0.001) and more pronounced mechanical dispersion (64 ± 22 vs. 36 ± 13 ms, P < 0.001) compared with healthy individuals. VAs were documented in 37 (25%) HCM patients. Patients with VAs had worse GLS (−14.1 ± 3.6% vs. −16.3 ± 3.4%, P < 0.01), more pronounced mechanical dispersion (79 ± 27 vs. 59 ± 16 ms, P < 0.001), and higher %LGE (6.1 ± 7.8% vs. 0.5 ± 1.4%, P < 0.001) than patients without VAs. Mechanical dispersion correlated with %LGE (R = 0.52, P < 0.001) and was independently associated with VAs (OR 1.6, 95% CI 1.1–2.3, P = 0.02) and improved risk stratification for VAs. Conclusion GLS, mechanical dispersion, and LGE were markers of VAs in HCM patients. Mechanical dispersion was a strong independent predictor of VAs and related to the extent of fibrosis. Strain echocardiography may improve risk stratification of VAs in HCM.

Risk prediction of ventricular arrhythmias and myocardial function in Lamin A/C mutation positive subjects

AIMS Mutations in the Lamin A/C gene may cause atrioventricular block, supraventricular arrhythmias, ventricular arrhythmias (VA), and dilated cardiomyopathy. We aimed to explore the predictors and the mechanisms of VA in Lamin A/C mutation-positive subjects. METHODS AND RESULTS We included 41 Lamin A/C mutation-positive subjects. PR-interval and occurrence of VA were recorded. Left ventricular (LV) myocardial function was assessed as ejection fraction and speckle tracking longitudinal strain by echocardiography. Magnetic resonance imaging was performed to assess fibrosis in a selection of subjects. Ventricular arrhythmias were documented in 21 patients (51%). Prolonged PR-interval was the best predictor of VA (P < 0.001). Myocardial function by strain was reduced in the interventricular septum compared with the rest of the LV segments (-16.7% vs. -18.7%, P = 0.001) and correlated to PR-interval (R = 0.41, P = 0.03). Myocardial fibrosis was found exclusively in the interventricular septum and only in patients with VA (P = 0.007). PR-interval was longer in patients with septal fibrosis compared with those without (320 ± 66 vs. 177 ± 40 ms, P < 0.001). CONCLUSION Prolonged PR-interval was the best predictor of VA in Lamin A/C mutation-positive subjects. Electrical, mechanical, and structural cardiac properties were related in these subjects. Myocardial function was most reduced in the interventricular septum and correlated to prolonged PR-interval. Myocardial septal fibrosis was associated with prolonged PR-interval and VA. Localized fibrosis in the interventricular septum may be the mechanism behind reduced septal function, atrioventricular block and VA in Lamin A/C mutation-positive subjects.

Left ventricular markers of mortality and ventricular arrhythmias in heart failure patients with cardiac resynchronization therapy

Aims Cardiac resynchronization therapy (CRT) reduces morbidity and mortality in heart failure. However, prediction of the outcome remains difficult. We aimed to investigate for echocardiographic predictors of ventricular arrhythmias and fatal outcome and to explore how myocardial function is changed by biventricular pacing in heart failure. Methods and results We prospectively included 170 heart failure patients (66 ± 10 years, New York Heart Association class 2.8 ± 0.5, 48% ischaemic cardiomyopathy) and recorded ventricular arrhythmias and fatal end point defined as death, heart transplantation, or left ventricular assist device implantation during 2 years. Two-dimensional echocardiography was performed before and 6 months after CRT implantation. CRT response was defined as ≥15% reduction in end-systolic volume at 6 months. Speckle-tracking technique was performed to assess longitudinal and circumferential left ventricular function, defined as global longitudinal (GLS) and circumferential strain (GCS), and to assess mechanical dyssynchrony, defined as mechanical dispersion. GLS before CRT was a predictor of fatal end point independently of CRT response [hazard ratio, HR 1.14 (1.02–1.27), P = 0.02]. Patients with GLS better than −8.3% showed event-free survival benefit (log rank, P < 0.001). Mechanical dispersion at 6 months was an independent predictor of ventricular arrhythmias [HR 1.20 (1.06–1.35), P = 0.005]. CRT responders (59%) had improvement of both GLS and GCS. Conclusion In heart failure patients with CRT, worse longitudinal function before CRT was an important predictor of fatal outcome during 2 years, independently of CRT response. Mechanical dispersion at 6 months was a strong predictor of ventricular arrhythmias. CRT response by reverse remodelling was dependent on improvement of both longitudinal and circumferential function.

Lamin A/C cardiomyopathy: young onset, high penetrance, and frequent need for heart transplantation

Abstract Aims Lamin A/C (LMNA) mutations cause familial dilated cardiomyopathy (DCM) with frequent conduction blocks and arrhythmias. We explored the prevalence, cardiac penetrance, and expressivity of LMNA mutations among familial DCM in Norway. Furthermore, we explored the risk factors and the outcomes in LMNA patients. Methods and results During 2003–15, genetic testing was performed in patients referred for familial DCM. LMNA genotype-positive subjects were examined by electrocardiography, Holter monitoring, cardiac magnetic resonance imaging, and echocardiography. A positive cardiac phenotype was defined as the presence of atrioventricular (AV) block, atrial fibrillation/flutter (AF), ventricular tachycardia (VT), and/or echocardiographic DCM. Heart transplantation was recorded and compared with non-ischaemic DCM of other origin. Of 561 unrelated familial DCM probands, 35 (6.2%) had an LMNA mutation. Family screening diagnosed an additional 93 LMNA genotype-positive family members. We clinically followed up 79 LMNA genotype-positive [age 42 ± 16 years, ejection fraction (EF) 45 ± 13%], including 44 (56%) with VT. Asymptomatic LMNA genotype-positive family members (age 31 ± 15 years) had a 9% annual incidence of a newly documented cardiac phenotype and 61% (19/31) of cardiac penetrance during 4.4 ± 2.9 years of follow-up. Ten (32%) had AV block, 7 (23%) AF, and 12 (39%) non-sustained VT. Heart transplantation was performed in 15 of 79 (19%) LMNA patients during 7.8 ± 6.3 years of follow-up. Conclusion LMNA mutation prevalence was 6.2% of familial DCM in Norway. Cardiac penetrance was high in young asymptomatic LMNA genotype-positive family members with frequent AV block and VT, highlighting the importance of early family screening and cardiological follow-up. Nearly 20% of the LMNA patients required heart transplantation.

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

BackgroundCrisis 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.MethodsThe 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.ResultsThe 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.ConclusionsOur 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.

Psychiatric admissions from crisis resolution teams in Norway: a prospective multicentre study

BackgroundCrisis resolution teams (CRTs) provide intensive alternative care to hospital admission for patients with mental health crises. The aims of this study were to describe the proportions and characteristics of patients admitted to in-patient wards from CRTs, to identify any differences in admission practices between CRTs, and to identify predictors of admissions from CRTs.MethodsA naturalistic prospective multicentre design was used to study 680 consecutive patients under the care of eight CRTs in Norway over a 3-month period in 2005/2006. Socio-demographic and clinical data were collected on the patients, and on the organization and operation of the CRTs. Logistic regression analysis for hierarchical data was used to test potential predictors of admission at team and patient level.ResultsOne hundred and forty-six patients (21.5%) were admitted to in-patient wards. There were significant differences in admission rates between the CRTs. The likelihood of being admitted to an in-patient ward was significantly lower for patients treated by CRTs that operated during extended opening hours than CRTs that operated during office hours only. Those most likely to be admitted were patients with psychotic symptoms, suicidal risk, and a prior history of admissions.ConclusionsExtended opening hours may help CRTs to prevent more admissions for patients with moderately severe and relapsing mental illnesses. Patients with severe psychosis seem to be difficult to treat in the community by Norwegian CRTs even with extended opening hours.

Kardiomyopati ved arvelig skjelettmuskeldystrofi

En rekke genetiske skjelettmuskeldystrofier er assosiert med kardiomyopati med hjertesviktutvikling og risiko for plutselig død. Grad av kardial affeksjon er ikke nødvendigvis relatert til grad av skjelettmuskelaffeksjon, og plutselig hjertedød kan være første tegn på kardiomyopati. For å iverksette behandling og forebyggende tiltak mot livstruende kardiale hendelser er det nødvendig med økt oppmerksomhet blant allmennleger og spesialister.

The systolic paradox in hypertrophic cardiomyopathy

Objective We explored cardiac volumes and the effects on systolic function in hypertrophic cardiomyopathy (HCM) patients with left ventricular hypertrophy (HCM LVH+) and genotype-positive patients without left ventricular hypertrophy (HCM LVH−). Methods We included 180 HCM LVH+, 100 HCM LVH− patients and 80 healthy individuals. End-Diastolic Volume Index (EDVI), End-Systolic Volume Index (ESVI) and ejection fraction (EF) were assessed by echocardiography. Left ventricular (LV) global longitudinal strain (GLS) was measured by speckle tracking echocardiography. Results EDVI and ESVI were significantly smaller in HCM LVH+ compared with HCM LVH− patients (41±14 mL/m2 vs 49±13 mL/m2 and 16±7 mL/m2 vs 19±6 mL/m2, respectively, both p<0.001) and in healthy individuals (41±14 mL/m2 vs 57±14 mL/m2 and 16±7 mL/m2 vs 23±9 mL/m2, respectively, both p<0.001). HCM LVH− patients had significantly lower EDVI and ESVI compared with healthy individuals (49±13 mL/m2 vs 57±14 mL/m2 and 19±6 mL/m2 vs 23±9 mL/m2, both p<0.001). EF was similar (61%±7% vs 60%±8% vs 61%±6%, p=0.43) in the HCM LVH+, HCM LVH– and healthy individuals, despite significantly worse GLS in the HCM LVH+ (−16.4%±3.7% vs −21.3%±2.4% vs −22.3%±3.7%, p<0.001). GLS was worse in the HCM LVH− compared with healthy individuals in pairwise comparison (p=0.001). Decrease in ESVI was closely related to EF in HCM LVH+ and HCM LVH− (R=0.45, p<0.001 and R=0.43, p<0.001) as expected, but there was no relationship with GLS (R=0.02, p=0.77 and R=0.11, p=0.31). Increased maximal wall thickness (MWT) correlated significantly with worse GLS (R=0.58, p<0.001), but not with EF (R=0.018, p=0.30) in the HCM LVH+ patients. Conclusion HCM LVH+ had smaller cardiac volumes that could explain the preserved EF, despite worse GLS that was closely related to MWT. HCM LVH− had reduced cardiac volumes and subtle changes in GLS compared with healthy individuals, indicating a continuum of both volumetric and systolic changes present before increased MWT.