A woman in her fifties with cirrhosis of the liver and postural dyspnoea. / En kvinne i 50-årene med levercirrhose og stillingsavhengig dyspné.

A woman in her fifties with advanced cirrhosis of the liver was admitted multiple times with recurrent pleural effusion and ascites. She was accepted for liver transplantation, at which time she developed postural dyspnoea and a drop in oxygen saturation.

Left atrial appendage strain predicts subclinical atrial fibrillation in embolic strokes of undetermined source.

Aims: Left atrial (LA) strain is promising in prediction of clinical atrial fibrillation (AF) in stroke patients. However, prediction of subclinical AF is critical in patients with embolic strokes of undetermined source (ESUS). The aim of this prospective study was to investigate novel LA and left atrial appendage (LAA) strain markers in prediction of subclinical AF in ESUS patients. Methods and results: A total of 185 patients with ESUS, mean age 68 ± 13years, 33% female, without diagnosed AF, were included. LAA and LA function by conventional echocardiographic parameters and reservoir strain (Sr), conduit strain (Scd), contraction strain (Sct), and mechanical dispersion (MD) of Sr were assessed with transoesophageal and transthoracic echocardiography. Subclinical AF was detected by insertable cardiac monitors during follow-up. LAA strain was impaired in 60 (32%) patients with subclinical AF compared to those with sinus rhythm: LAA-Sr, 19.2 ± 4.5% vs. 25.6 ± 6.5% (P < 0.001); LAA-Scd, -11.0 ± 3.1% vs. -14.4 ± 4.5% (P < 0.001); and LAA-Sct, -7.9 ± 4.0% vs. -11.2 ± 4% (P < 0.001), respectively, while LAA-MD was increased, 34 ± 24 ms vs. 26 ± 20 ms (P = 0.02). However, there was no significant difference in phasic LA strain or LA-MD. By ROC analyses, LAA-Sr was highly significant in prediction of subclinical AF and showed the best AUC of 0.80 (95% CI 0.73-0.87) with a sensitivity of 80% and a specificity of 73% (P < 0.001). LAA-Sr and LAA-MD were both independent and incremental markers of subclinical AF in ESUS patients. Conclusion: LAA function by strain and mechanical dispersion predicted subclinical AF in ESUS patients. These novel echocardiographic markers may improve risk stratification in ESUS patients.

Scar imaging in the dyssynchronous left ventricle: Accuracy of myocardial metabolism by positron emission tomography and function by echocardiographic strain.

PURPOSE: Response to cardiac resynchronization therapy (CRT) is reduced in patients with high left ventricular (LV) scar burden, in particular when scar is located in the LV lateral wall or septum. Late gadolinium enhancement (LGE) cardiac magnetic resonance (CMR) can identity scar, but is not feasible in all patients. This study investigates if myocardial metabolism by 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) and contractile function by echocardiographic strain are alternatives to LGE-CMR. METHODS: In a prospective multicenter study, 132 CRT candidates (91% with left bundle branch block) were studied by speckle tracking strain echocardiography, and 53 of these by FDG-PET. Regional myocardial FDG metabolism and peak systolic strain were compared to LGE-CMR as reference method. RESULTS: Reduced FDG metabolism (<70% relative) precisely identified transmural scars (≥50% of myocardial volume) in the LV lateral wall, with area under the curve (AUC) 0.96 (95% confidence interval (CI) 0.90-1.00). Reduced contractile function by strain identified transmural scars in the LV lateral wall with only moderate accuracy (AUC = 0.77, CI 0.71-0.84). However, absolute peak systolic strain >10% could rule out transmural scar with high sensitivity (80%) and high negative predictive value (96%). Neither FDG-PET nor strain identified septal scars (for both, AUC < 0.80). CONCLUSIONS: In CRT candidates, FDG-PET is an excellent alternative to LGE-CMR to identify scar in the LV lateral wall. Furthermore, preserved strain in the LV lateral wall has good accuracy to rule out transmural scar. None of the modalities can identify septal scar. CLINICAL TRIAL REGISTRATION: The present study is part of the clinical study "Contractile Reserve in Dyssynchrony: A Novel Principle to Identify Candidates for Cardiac Resynchronization Therapy (CRID-CRT)", which was registered at clinicaltrials.gov (identifier NCT02525185).

Harmful Effects of Exercise Intensity and Exercise Duration in Patients With Arrhythmogenic Cardiomyopathy.

OBJECTIVES: The goal of this study was to explore the association between exercise duration versus exercise intensity and adverse outcome in patients with arrhythmogenic cardiomyopathy (AC). BACKGROUND: Vigorous exercise aggravates and accelerates AC, but there are no data assessing the harmful effects of exercise intensity and duration in these patients. METHODS: Exercise habits at time of diagnosis were recorded by standardized interviews in consecutive AC patients. Exercise >6 metabolic equivalents was defined as high intensity, and exercise duration was categorized as long if above median. Life-threatening ventricular arrhythmia (VA) was defined as aborted cardiac arrest, documented sustained ventricular tachycardia, ventricular fibrillation, or appropriate implantable cardioverter-defibrillator therapy. RESULTS: We included 173 AC patients (53% probands; 44% female; 41 ± 16 years of age). Median weekly exercise duration was 2.5 h (interquartile range: 2.0 to 5.5 h), and 91 patients (52%) reported high-intensity exercise. VA had occurred in 83 patients (48%) and was more prevalent in patients with high-intensity exercise than low-intensity exercise (74% vs. 20%, p < 0.001), and more prevalent in long-duration than short-duration exercise (65% vs. 31%, p < 0.001). High-intensity exercise was a strong and independent marker of VA, even when adjusted for the interaction with long-duration exercise (odds ratio: 3.8; 95% confidence interval: 1.3 to 11.0, p < 0.001), whereas long-duration exercise was not. CONCLUSIONS: High-intensity exercise was a strong and independent marker of life-threatening VA in AC patients, independent of exercise duration. AC patients could be advised to restrict their exercise intensity.

Morphological changes and myocardial function assessed by traditional and novel echocardiographic methods in preadolescent athlete's heart.

Background Athlete's heart is a term used to describe the morphological and functional changes in the hearts of athletes. Recent studies suggest that these changes may occur even in preadolescent athletes. This study aims to improve our understanding of the changes occurring in the preadolescent athlete's heart. Design and methods Cardiac morphology and function in 76 preadolescent cross-country skiers (aged 12.1 ± 0.2 years) were compared with 25 age-matched non-competing preadolescents. Echocardiography was performed in all subjects, including 2D speckle-tracking strain echocardiography and 3D echocardiography. All participants underwent cardiopulmonary exercise testing to assess oxygen uptake and exercise capacity. Results Athletes had greater indexed VO2 max (62 ± 7 vs. 44 ± 5 mL/kg per min, p < 0.001), indexed left ventricular end-diastolic volume (79 ± 7 vs. 68 ± 7 mL/m2, p < 0.001), left ventricular mass (69 ± 12 vs. 57 ± 13 g/m2, p < 0.001), indexed right ventricular basal diameter (28.3 ± 3.0 vs. 25.4 ± 3.5 mm/m2, p < 0.001) and right atrial area (10.6 ± 1.4 vs. 9.7 ± 1.2 cm2/m2, p < 0.01). There was no difference in left ventricular ejection fraction, global longitudinal strain, and global circumferential strain and right ventricular fractional area change between the groups. Controls had higher right ventricular global longitudinal strain (-28.1 ± 3.5 vs. -31.1 ± 3.3%, p < 0.01). VO2 max was highly correlated to left ventricular end-diastolic volume ( r = 0.76, p < 0.001). Conclusion Athletes had greater left ventricular mass and greater left and right ventricular chamber dimensions compared with controls, while left ventricular function did not differ. Interestingly, right ventricular deformation was significantly lower compared with controls. This supports the notion that there is physiological, adaptive remodelling in preadolescent athlete's heart.

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

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.

Lower than expected burden of premature ventricular contractions impairs myocardial function.

AIMS: We aimed to explore the burden of frequent premature ventricular contractions (PVCs) associated with myocardial dysfunction in patients with outflow tract arrhythmia (OTA). We hypothesized that this threshold is lower than the previously suggested threshold of 24 000 PVCs/24 h (24%PVC) when systolic function is assessed by strain echocardiography. Furthermore, we aimed to characterize OTA patients with malignant arrhythmic events. METHODS AND RESULTS: We included 52 patients referred for OTA ablation (46 ± 12 years, 58% female). Left ventricular global longitudinal strain (GLS) and mechanical dispersion were assessed by speckle tracking echocardiography. A subset underwent cardiac magnetic resonance imaging. PVC burden (%PVC) was assessed by Holter recording. Sinus rhythm QRS duration and PVC QRS duration were recorded from electrocardiogram, and the ratio was calculated (PVC QRS duration / sinus rhythm QRS duration). Median %PVC was 7.2 (0.2-60.0%). %PVC correlated with GLS (R = 0.44, P = 0.002) and with mechanical dispersion (R = 0.48, P < 0.001), but not with ejection fraction (R = 0.22, P = 0.12). %PVC was higher in patients with impaired systolic function by GLS (worse than -18%) compared with patients with normal function (22% vs. 5%, P = 0.001). Greater than 8%PVC optimally identified patients with abnormal GLS (area under the curve 0.79). Serious arrhythmic events occurred in 11/52 (21%) patients characterized by high QRS ratios (1.56 vs. 1.91, P < 0.001). CONCLUSIONS: More than 8%PVC was associated with impaired systolic function by GLS, which is a lower threshold than previously reported. Patients with serious arrhythmic events had higher QRS ratios, which may represent a more malignant phenotype of OTA.

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.

Soluble ST2 is associated with disease severity in arrhythmogenic right ventricular cardiomyopathy.

PURPOSE: Diagnostic and prognostic evaluation remains challenging in arrhythmogenic right ventricular cardiomyopathy (ARVC). We measured plasma concentration of soluble ST2 (sST2) and assessed its association with right ventricular (RV) function and ventricular arrhythmias in patients with ARVC. METHODS: We included patients with ARVC and genotype positive relatives. Soluble ST2 was determined by ELISA. We assessed myocardial function by echocardiography including strain by speckle tracking technique. RESULTS: We included 44 subjects (age 41 ± 15 years, 21 (48%) female). Soluble ST2 was associated with RV global strain (r = 0.44; p = 0.008), as well as with left ventricular (LV) function. Plasma levels of sST2 were higher in patients with ventricular arrhythmias than in patients without ventricular arrhythmias (35 ± 13 ng/mL vs. 26 ± 7 ng/mL, p = 0.009). The association between sST2 and ventricular arrhythmias remained significant even after adjusting for RV function (Wald = 5.2; p = 0.02). CONCLUSIONS: Soluble ST2 is associated with RV and LV function in patients with ARVC. Soluble ST2 may aid in the determination of disease severity in ARVC.

Comparison of patients with early-phase arrhythmogenic right ventricular cardiomyopathy and right ventricular outflow tract ventricular tachycardia.

AIMS: Differentiation between early-phase arrhythmogenic right ventricular cardiomyopathy (ARVC) and right ventricular outflow tract (RVOT)-ventricular tachycardia (VT) can be challenging, and correct diagnosis is important. We compared electrocardiogram (ECG) parameters and morphological right ventricular (RV) abnormalities and investigated if ECG and cardiac imaging can help to discriminate early-phase ARVC from RVOT-VT patients. METHODS AND RESULTS: We included 44 consecutive RVOT-VT (47 ± 14 years) and 121 ARVC patients (42 ± 17 years). Of the ARVC patients, 77 had definite ARVC and 44 had early-phase ARVC disease. All underwent clinical examination, ECG, and Holter monitoring. Frequency of premature ventricular complexes (PVC) was expressed as percent per total beats/24 h (%PVC), and PVC configuration was recorded. By echocardiography, we assessed indexed RV basal diameter (RVD), indexed RVOT diameter, and RV and left ventricular (LV) function. RV mechanical dispersion (RVMD), reflecting RV contraction heterogeneity, was assessed by speckle-tracking strain echocardiography. RV ejection fraction (RVEF) was assessed by cardiac magnetic resonance imaging (CMR). Patients with early-phase ARVC had lower %PVC by Holter and PVC more frequently originated from the RV lateral free wall (both P < 0.001). RVD was larger (21 ± 3 vs. 19 ± 2 mm, P < 0.01), RVMD was more pronounced (22 ± 15 vs. 15 ± 13 ms, P = 0.03), and RVEF by CMR was decreased (41 ± 8 vs. 49 ± 4%, P < 0.001) in early-phase ARVC vs. RVOT-VT patients. CONCLUSION: Patients with early-phase ARVC had structural abnormalities with lower RVEF, increased RVD, and pronounced RVMD in addition to lower %PVC by Holter compared with RVOT-VT patients. These parameters can help correct diagnosis in patients with unclear phenotypes.

Combination of ECG and Echocardiography for Identification of Arrhythmic Events in Early ARVC.

OBJECTIVES: The aim of this study was to investigate early markers of arrhythmic events (AEs) and improve risk stratification in early arrhythmogenic right ventricular cardiomyopathy (ARVC). BACKGROUND: AEs are frequent in patients with ARVC, but risk stratification in subjects with early ARVC is challenging. METHODS: Early ARVC disease was defined as possible or borderline ARVC diagnosis according to the ARVC Task Force Criteria 2010. We performed resting and signal averaged electrocardiogram (ECG). Using echocardiography, we assessed right ventricular (RV) outflow tract diameter and right ventricular basal diameter (RV diameter). Global longitudinal strain and mechanical dispersion (MD) from strain echocardiography were assessed in both the right and left ventricle. AEs were defined as documented ventricular tachycardia, cardiac syncope, or aborted cardiac arrest. RESULTS: Of 162 included subjects with ARVC (41 ± 16 years of age, 47% female), 73 had early ARVC, including mutation positive family members not fulfilling definite ARVC diagnosis. AEs occurred in 15 (21%) subjects with early ARVC. Those with AEs in early disease had larger RV diameter (40 ± 4 mm vs. 37 ± 5 mm), more pronounced RVMD (39 ± 15 ms vs. 26 ± 11 ms), and more pathological signal averaged ECGs compared with those without AEs (all p ≤ 0.05). Adding measurements of RV diameter and RVMD to electrical parameters improved identification of subjects with AEs compared with electrical parameters alone (p = 0.05). CONCLUSIONS: ECG parameters, RV diameter, and RVMD were markers of previous arrhythmic events in patients with early ARVC. A combination of electrical and echocardiographic parameters improved identification of subjects with AEs in early ARVC disease.

Echocardiographic comparison between left ventricular non-compaction and hypertrophic cardiomyopathy.

BACKGROUND: Modern imaging technology has improved detection of left ventricular non-compaction cardiomyopathy (LVNC). Hypertrophic cardiomyopathy (HCM) shares morphological features with LVNC, but prognosis and treatment strategies differ between LVNC and HCM. METHODS AND RESULTS: We aimed to compare global and regional LV myocardial function in LVNC and HCM. We hypothesized that apical function is reduced in LVNC due to the embryonic reduced compaction of the apex. We studied 25 patients with LVNC (47±14years) according to current criteria, 50 with HCM (47±14years) and 50 healthy individuals (49±19years). By echocardiography, we assessed maximal wall thickness (MWT) and LV ejection fraction (EF). Numbers of trabeculations were counted from 3 apical views. Global longitudinal strain by speckle tracking echocardiography was calculated from a 16 LV segments model. LV basal (6 segments) and apical (4 segments) longitudinal strains were averaged. MWT was thinner, EF lower and trabeculations were more pronounced in LVNC compared to HCM (all p<0.001) but with no significantly differences in LV global longitudinal strain (-15.1±6.1 vs. -16.8±3.7, p=0.14). Function by longitudinal strain increased significantly from base to apex in HCM (-14.9±4.3% vs. -19.5±4.7%, p<0.001) and in healthy controls (-20.0±1.9% vs. -21.8±2.9%, p<0.001), but not in LVNC (-14.7±6.4% vs. -15.7±7.2%, p=0.35). CONCLUSIONS: Increased number of trabeculations, thinner MWT and lower EF were characteristics of LVNC. Myocardial function was homogeneously reduced in LVNC, while an apical to basal gradient with relatively preserved apical function was present in HCM. These characteristics may help to discriminate between LVNC and HCM.

Ventricular structure in ARVC: going beyond volumes as a measure of risk.

BACKGROUND: Altered right ventricular structure is an important feature of Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC), but is challenging to quantify objectively. The aim of this study was to go beyond ventricular volumes and diameters and to explore if the shape of the right and left ventricles could be assessed and related to clinical measures. We used quantifiable computational methods to automatically identify and analyse malformations in ARVC patients from Cardiovascular Magnetic Resonance (CMR) images. Furthermore, we investigated how automatically extracted structural features were related to arrhythmic events. METHODS: A retrospective cross-sectional feasibility study was performed on CMR short axis cine images of 27 ARVC patients and 21 ageing asymptomatic control subjects. All images were segmented at the end-diastolic (ED) and end-systolic (ES) phases of the cardiac cycle to create three-dimensional (3D) bi-ventricle shape models for each subject. The most common components to single- and bi-ventricular shape in the ARVC population were identified and compared to those obtained from the control group. The correlations were calculated between identified ARVC shapes and parameters from the 2010 Task Force Criteria, in addition to clinical outcomes such as ventricular arrhythmias. RESULTS: Bi-ventricle shape for the ARVC population showed, as ordered by prevalence with the percent of total variance in the population explained by each shape: global dilation/shrinking of both ventricles (44 %), elongation/shortening at the right ventricle (RV) outflow tract (15 %), tilting at the septum (10 %), shortening/lengthening of both ventricles (7 %), and bulging/shortening at both the RV inflow and outflow (5 %). Bi-ventricle shapes were significantly correlated to several clinical diagnostic parameters and outcomes, including (but not limited to) correlations between global dilation and electrocardiography (ECG) major criteria (p = 0.002), and base-to-apex lengthening and history of arrhythmias (p = 0.003). Classification of ARVC vs. control using shape modes yielded high sensitivity (96 %) and moderate specificity (81 %). CONCLUSION: We presented for the first time an automatic method for quantifying and analysing ventricular shapes in ARVC patients from CMR images. Specific ventricular shape features were highly correlated with diagnostic indices in ARVC patients and yielded high classification sensitivity. Ventricular shape analysis may be a novel approach to classify ARVC disease, and may be used in diagnosis and in risk stratification for ventricular arrhythmias.

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.

Nadolol decreases the incidence and severity of ventricular arrhythmias during exercise stress testing compared with ß1-selective ß-blockers in patients with catecholaminergic polymorphic ventricular tachycardia.

BACKGROUND: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inheritable cardiac disease predisposing to malignant ventricular arrhythmias. OBJECTIVE: We aimed to explore the incidence and severity of ventricular arrhythmias in patients with CPVT before the initiation of ß-blocker treatment, when treated with ß1-selective ß-blockers, and when treated with nadolol. METHODS: In this study, 34 patients with CPVT were included (mean age 34 ± 19 years; 15 (44%) women; 30 (88%) ryanodine receptor 2 variant positive). We performed 3 bicycle exercise stress tests in each patient: (1) before the initiation of ß-blocker treatment, (2) after >6 weeks of treatment with ß1-selective ß-blockers and (3) after >6 weeks of treatment with nadolol. We recorded resting and maximum heart rates and the most severe ventricular arrhythmia occurring. Severity of arrhythmias was scored as 1 point for no arrhythmias or only single ventricular extrasystoles, 2 points for >10 ventricular extrasystoles per minute or bigeminy, 3 points for couplets, and 4 points for nonsustained ventricular tachycardia or sustained ventricular tachycardia. RESULTS: Resting heart rate was similar during treatment with nadolol and ß1-selective ß-blockers (54 ± 10 beats/min vs 56 ± 14 beats/min; P = .50), while maximum heart rate was lower during treatment with nadolol compared with ß1-selective ß-blockers (122 ± 21 beats/min vs 139 ± 24 beats/min; P = .001). Arrhythmias during exercise stress testing were less severe during treatment with nadolol compared with during treatment with ß1-selective ß-blockers (arrhythmic score 1.6 ± 0.9 vs 2.5 ± 0.8; P < .001) and before the initiation of ß-blocker treatment (arrhythmic score 1.6 ± 0.9 vs 2.7 ± 0.9; P = .001); however, no differences were observed during treatment with ß1-selective ß-blockers compared with before the initiation of ß-blocker treatment (arrhythmic score 2.5 ± 0.8 vs 2.7 ± 0.9; P = .46). CONCLUSION: The incidence and severity of ventricular arrhythmias decreased during treatment with nadolol compared with during treatment with ß1-selective ß-blockers. ß1-Selective ß-blockers did not change the occurrence or severity of arrhythmias compared with no medication.

Arrhythmogenic right ventricular cardiomyopathy, clinical manifestations, and diagnosis.

This review aims to give an update on the pathogenesis, clinical manifestations, and diagnosis of arrhythmogenic right ventricular cardiomyopathy (ARVC). Arrhythmogenic right ventricular cardiomyopathy is mainly an autosomal dominant inherited disease linked to mutations in genes encoding desmosomes or desmosome-related proteins. Classic symptoms include palpitations, cardiac syncope, and aborted cardiac arrest due to ventricular arrhythmias. Heart failure may develop in later stages. Diagnosis is based on the presence of major and minor criteria from the Task Force Criteria revised in 2010 (TFC 2010), which includes evaluation of findings from six different diagnostic categories. Based on this, patients are classified as having possible, borderline, or definite ARVC. Imaging is important in ARVC diagnosis, including both echocardiography and cardiac magnetic resonance imaging for detecting structural and functional abnormalities, but importantly these findings may occur after electrical alterations and ventricular arrhythmias. Electrocardiograms (ECGs) and signal-averaged ECGs are analysed for depolarization and repolarization abnormalities, including T-wave inversions as the most common ECG alteration. Ventricular arrhythmias are common in ARVC and are considered a major diagnostic criterion if originating from the RV inferior wall or apex. Family history of ARVC and detection of an ARVC-related mutation are included in the TFC 2010 and emphasize the importance of family screening. Electrophysiological studies are not included in the diagnostic criteria, but may be important for differential diagnosis including RV outflow tract tachycardia. Further differential diagnoses include sarcoidosis, congenital abnormalities, myocarditis, pulmonary hypertension, dilated cardiomyopathy, and athletic cardiac adaptation, which may mimic ARVC.

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

OBJECTIVES: This study aimed to explore systolic and diastolic function and to investigate genotype-specific differences in subjects with long QT syndrome (LQTS). BACKGROUND: LQTS 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. METHODS: We 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. RESULTS: Systolic 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/m(2) vs. 26 ± 5 ml/m(2), p = 0.01), also when adjusted for age and other possible confounders. CONCLUSIONS: Subjects 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.

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

AIMS: 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. METHODS AND RESULTS: We included 110 subjects (age 42 ± 17 years), 65 ARVC patients and 45 mutation-positive family members. Athletes were defined as subjects with ≥4 h vigorous exercise/week [≥1440 metabolic equivalents (METs × minutes/week)] during a minimum of 6 years. Athlete definition was fulfilled in 37/110 (34%) subjects. We assessed right ventricular (RV) and left ventricular (LV) myocardial function by echocardiography, and by magnetic resonance imaging (MRI). The RV function by RV fractional area change (FAC), RV global longitudinal strain (GLS) by echocardiography, and RV ejection fraction (EF) by MRI was reduced in athletes compared with non-athletes (FAC 34 ± 9% vs. 40 ± 11%, RVGLS -18.3 ± 6.1% vs. -22.0 ± 4.8%, RVEF 32 ± 8% vs. 43 ± 10%, all P < 0.01). LV function by LVEF and LVGLS was reduced in athletes compared with non-athletes (LVEF by echocardiography 50 ± 10% vs. 57 ± 5%, LVEF by MRI 46 ± 6% vs. 53 ± 8%, and LVGLS -16.7 ± 4.2% vs. -19.4 ± 2.9%, all P < 0.01). The METs × minutes/week correlated with reduced RV and LV function by echocardiography and MRI (all P < 0.01). The LVEF by MRI was also reduced in subgroups of athlete index patients (46 ± 7% vs. 54 ± 10%, P = 0.02) and in athlete family members (47 ± 3% vs. 52 ± 6%, P < 0.05). CONCLUSION: Athletes showed reduced biventricular function compared with non-athletes in ARVC patients and in mutation-positive family members. The amount and intensity of exercise activity was associated with impaired LV and RV function. Exercise may aggravate and accelerate myocardial dysfunction in ARVC.