Strain echocardiography improves prediction of arrhythmic events in ischemic and non-ischemic dilated cardiomyopathy.

BACKGROUND: Recent evidence suggests that an implantable cardioverter defibrillator (ICD) in non-ischemic cardiomyopathy (NICM) may not offer mortality benefit. We aimed to investigate if etiology of heart failure and strain echocardiography can improve risk stratification of life threatening ventricular arrhythmia (VA) in heart failure patients. METHODS: This prospective multi-center follow-up study consecutively included NICM and ischemic cardiomyopathy (ICM) patients with left ventricular ejection fraction (LVEF) <40%. We assessed LVEF, global longitudinal strain (GLS) and mechanical dispersion (MD) by echocardiography. Ventricular arrhythmia was defined as sustained ventricular tachycardia, sudden cardiac death or appropriate shock from an ICD. RESULTS: We included 290 patients (67 ± 13 years old, 74% males, 207(71%) ICM). During 22 ± 12 months follow up, VA occurred in 32(11%) patients. MD and GLS were both markers of VA in patients with ICM and NICM, whereas LVEF was not (p = 0.14). MD independently predicted VA (HR: 1.19; 95% CI 1.08-1.32, p = 0.001), with excellent arrhythmia free survival in patients with MD <70 ms (Log rank p < 0.001). Patients with NICM and MD <70 ms had the lowest VA incidence with an event rate of 3%/year, while patients with ICM and MD >70 ms had highest VA incidence with an event rate of 16%/year. CONCLUSION: Patients with NICM and normal MD had low arrhythmic event rate, comparable to the general population. Patients with ICM and MD >70 ms had the highest risk of VA. Combining heart failure etiology and strain echocardiography may classify heart failure patients in low, intermediate and high risk of VA and thereby aid ICD decision strategies.

Implantable cardioverter-defibrillators in previously undiagnosed patients with catecholaminergic polymorphic ventricular tachycardia resuscitated from sudden cardiac arrest.

AIMS: In patients with catecholaminergic polymorphic ventricular tachycardia (CPVT), implantable cardioverter-defibrillator (ICD) shocks are sometimes ineffective and may even trigger fatal electrical storms. We assessed the efficacy and complications of ICDs placed in patients with CPVT who presented with a sentinel event of sudden cardiac arrest (SCA) while undiagnosed and therefore untreated. METHODS AND RESULTS: We analysed 136 patients who presented with SCA and in whom CPVT was diagnosed subsequently, leading to the initiation of guideline-directed therapy, including ß-blockers, flecainide, and/or left cardiac sympathetic denervation. An ICD was implanted in 79 patients (58.1%). The primary outcome of the study was sudden cardiac death (SCD). The secondary outcomes were composite outcomes of SCD, SCA, appropriate ICD shocks, and syncope. After a median follow-up of 4.8 years, SCD had occurred in three patients (3.8%) with an ICD and none of the patients without an ICD (P = 0.1). SCD, SCA, or appropriate ICD shocks occurred in 37 patients (46.8%) with an ICD and 9 patients (15.8%) without an ICD (P < 0.0001). Inappropriate ICD shocks occurred in 19 patients (24.7%) and other device-related complications in 22 patients (28.9%). CONCLUSION: In previously undiagnosed patients with CPVT who presented with SCA, an ICD was not associated with improved survival. Instead, the ICD was associated with both a high rate of appropriate ICD shocks and inappropriate ICD shocks along with other device-related complications. Strict adherence to guideline-directed therapy without an ICD may provide adequate protection in these patients without all the potential disadvantages of an ICD.

Life-threatening arrhythmic presentation in patients with arrhythmogenic cardiomyopathy before and after entering the genomic era; a two-decade experience from a large volume center.

BACKGROUND: Arrhythmogenic cardiomyopathy (AC) is an inheritable progressive heart disease with high risk of life-threatening ventricular arrhythmia (VA). We aimed to explore the prevalence of VA as presenting event in patients with AC over two decades, symptoms preceding VA and compare the clinical presentations and rate of AC-diagnosis over time. METHODS: We included consecutive AC-patients from our tertiary referral center. We recorded clinical history, VA (aborted cardiac arrest, sustained ventricular tachycardia or appropriate implantable cardioverter-defibrillator therapy), cardiac symptoms preceding VA in AC, and compared the history of patients diagnosed before and after implementation of genetic testing. RESULTS: We included 179 consecutive AC-patients and mutation-positive family members (95 [53%] probands, 84 [45%] female, 49 ±â€¯17 years), 33 (18%) diagnosed before and 146 (82%) after genetic testing became available. VA led to the AC-diagnosis in 46 (26%), and was less prevalent after implementation of genetic testing (17[52%] vs. 29[20%], p < 0.001), also when adjusted for proband status (Adjusted OR 2.7, 95% CI 1.1-6.7, p = 0.03). Yearly rate of AC-diagnosis increased after implementation of genetic testing in probands (2.7 ±â€¯1.3 vs. 6.8 ±â€¯4.3, p = 0.01) and family members (0.7 ±â€¯1.1 vs. 7.7 ±â€¯5.9, p = 0.002). Most patients with VA (92%) reported cardiac symptoms prior to event, and exercise-induced syncope was the strongest marker of subsequent VA (Adjusted OR 5.3, 95% CI 1.7-16.4, p = 0.004). CONCLUSION: VA led to AC-diagnosis in 46% of probands and was preceded by cardiac symptoms in the majority of cases. Yearly rate of AC-diagnoses increased after the implementation of genetic testing and life-threatening presentation of AC-disease seemed to decrease.

Number of pregnancies and subsequent phenotype in a cross-sectional cohort of women with arrhythmogenic cardiomyopathy.

Aims: We aimed to assess the relation between number of pregnancies and cardiac structure, function, and arrhythmic events in women with arrhythmogenic cardiomyopathy (AC). Methods and results: We included female AC patients in a cross-sectional study. Number of pregnancies and pregnancy related symptoms were recorded. Ventricular arrhythmias were defined as aborted cardiac arrest, sustained ventricular tachycardia, or appropriate implantable cardioverter-defibrillator therapy. Right and left ventricular dimensions and function, including strain analyses, were assessed by echocardiography and magnetic resonance imaging. We created a new AC severity score to grade the severity of AC disease. We included 77 women (age 47 ± 16, 43 probands and 34 AC mutation positive female relatives), 19 ± 14 years after last pregnancy. Median number of pregnancies was 2 (0-4); 19 had no previous pregnancies, 16 had 1 pregnancy, 30 had 2, and 12 had ≥3 pregnancies. Presence of a definite AC diagnosis (P = 0.36), severity of AC disease (P = 0.53), and arrhythmic events (P = 0.25) did not differ between groups of pregnancies. Number of pregnancies was related to increased right ventricular outflow tract diameter in single variable analyses [odds ratio (OR) 1.76, 95% confidence interval (CI) 1.08-2.87; P = 0.02], but not when adjusted for body surface area and age (OR 1.56, 95% CI 0.91-2.66; P = 0.11). The number of pregnancies was not associated with any other measures of cardiac structure and function. Conclusion: Higher number of pregnancies did not seem to relate to a worse phenotype in women with AC.

Arrhythmia initiation in catecholaminergic polymorphic ventricular tachycardia type 1 depends on both heart rate and sympathetic stimulation.

AIMS: Catecholaminergic polymorphic ventricular tachycardia type 1 (CPVT1) predisposes to ventricular tachyarrhythmias (VTs) during high heart rates due to physical or psychological stress. The essential role of catecholaminergic effects on ventricular cardiomyocytes in this situation is well documented, but the importance of heart rate per se for arrhythmia initiation in CPVT1 is largely unexplored. METHODS AND RESULTS: Sixteen CPVT1 patients performed a bicycle stress-test. Occurrence of VT triggers, i.e. premature ventricular complexes (PVC), depended on high heart rate, with individual thresholds. Atrial pacing above the individual PVC threshold in three patients did not induce PVCs. The underlying mechanism for the clinical observation was explored using cardiomyocytes from mice with the RyR2-R2474S (RyR2-RS) mutation, which exhibit exercise-induced VTs. While rapid pacing increased the number of Ca2+ waves in both RyR2-RS and wild-type (p<0.05), ß-adrenoceptor (ßAR) stimulation induced more Ca2+ waves in RyR2-RS (p<0.05). Notably, Ca2+ waves occurred despite decreased sarcoplasmic reticulum (SR) Ca2+ content in RyR2-RS (p<0.05), suggesting increased cytosolic RyR2 Ca2+ sensitivity. A computational model of mouse ventricular cardiomyocyte electrophysiology reproduced the cellular CPVT1 phenotype when RyR2 Ca2+ sensitivity was increased. Importantly, diastolic fluctuations in phosphorylation of RyR2 and SR Ca2+ content determined Ca2+ wave initiation. These factors were modulated towards increased propensity for arrhythmia initiation by increased pacing rates, but even more by ßAR stimulation. CONCLUSION: In CPVT1, VT propensity depends on individual heart rate thresholds for PVCs. Through converging data from clinical exercise stress-testing, cellular studies and computational modelling, we confirm the heart rate-independent pro-arrhythmic effects of ßAR stimulation in CPVT1, but also identify an independent and synergistic contribution from effects of high heart rate.

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.

Prognostic Value of Left Ventricular Deformation Parameters in Patients with Severe Aortic Stenosis: A Pilot Study of the Usefulness of Strain Echocardiography.

BACKGROUND: In patients with aortic stenosis, subtle alterations in myocardial mechanics can be detected by speckle-tracking echocardiography before reduction of left ventricular ejection fraction (LVEF). METHODS: In this prospective study, 162 patients with aortic stenosis with an average aortic valve area of 0.7 ± 0.2 cm2 and a mean LVEF of 60 ± 11% were included. Global longitudinal strain (GLS) and mechanical dispersion (SD of time from Q/R on the electrocardiogram to peak strain in 16 left ventricular segments) were assessed using echocardiography, and all-cause mortality (n = 37) was recorded during 37 ± 13 months of follow-up. RESULTS: Overall, nonsurvivors had more pronounced mechanical dispersion and worse GLS compared with survivors (74 ± 24 vs 61 ± 18 msec [P < .01] and -14.5 ± 4.4% vs -16.7 ± 3.6% [P < .01], respectively). In the 42 conservatively treated patients without surgical aortic valve replacement, a similar pattern was observed in nonsurvivors versus survivors (mechanical dispersion, 80 ± 24 vs 57 ± 14 msec [P < .01]; GLS, -14.0 ± 4.9% vs -17.1 ± 3.8% [P = .04], respectively). Mechanical dispersion was significantly associated with mortality (hazard ratio per 10-msec increase, 1.23; 95% CI, 1.07-1.42; P < .01) in a Cox model adjusted for LVEF and with aortic valve replacement treatment as a time-dependent covariate. Continuous net reclassification improvement showed that mechanical dispersion was incremental to LVEF, GLS, and valvulo-arterial impedance when adjusting for aortic valve replacement treatment in the total population. CONCLUSION: Increased mechanical dispersion may be a risk marker providing novel prognostic information in patients with aortic stenosis.

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.

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.

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.

Mechanical Dispersion Assessed by Strain Echocardiography Is Associated with Malignant Arrhythmias in Chagas Cardiomyopathy.

BACKGROUND: Sudden death is one of the characteristics of Chagas disease (ChD). With the development of strategies for the prevention of malignant arrhythmias, especially with implantable cardioverter-defibrillators (ICDs), there is interest in developing strategies to predict sudden cardiac death. The aim of this study was to test the hypothesis that global longitudinal strain (GLS) and mechanical dispersion (MD) may be associated with malignant ventricular arrhythmias in patients with ChD. METHODS: A cross-sectional study was conducted including 62 patients with ChD who were separated into two groups according to ICD implantation status. Group 0 consisted of 34 patients with ChD without ICDs, and group 1 comprised 28 patients with ICDs. Complete echocardiographic studies, including GLS and MD measurements, were performed in all patients. RESULTS: Chamber dimensions, ejection fraction, and diastolic function showed no significant differences between patients with and those without ICDs. GLS was reduced in patients with ChD with ICDs compared with those without (P = .02). By receiver operating characteristic curve analyses, GLS identified patients with ChD with ICDs with sensitivity of 67% and specificity of 69%. MD was more pronounced in patients with ChD with ICDs compared with those without (P < .001), with a C statistic of 0.83 (95% CI, 0.71-0.91). MD > 57 msec detected ICD presence with sensitivity of 79% and specificity of 71% and was superior to GLS and ejection fraction (P < .05). In multivariate analysis, New York Heart Association functional class (odds ratio, 3.02; 95% CI, 1.09-8.39; P = .03), MD (odds ratio, 1.11; 95% CI, 1.04-1.19; P = .001), and GLS (odds ratio, 0.72; 95% CI, 0.54-0.96; P = .026) were significant and independently associated with malignant arrhythmic events. CONCLUSIONS: GLS and MD may add important information in the risk stratification of patients with ChD. The use of MD by strain echocardiography could be an attractive tool in the decision making for ICD placement as primary prevention for sudden cardiac death in patients with ChD.

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.

Strain echocardiographic assessment of left atrial function predicts recurrence of atrial fibrillation.

AIMS: We evaluated if a dispersed left atrial (LA) contraction pattern was related to atrial fibrillation (AF) in patients with normal left ventricular (LV) function, and normal or mildly enlarged left atrium. METHODS AND RESULTS: We included 61 patients with paroxysmal AF (PAF). Of these, 30 had not while 31 had recurrence of AF after radiofrequency ablation (RFA). Twenty healthy individuals were included for comparison. Echocardiography was performed in patients in sinus rhythm the day before RFA. LA volume was calculated. Peak negative longitudinal strain was assessed in 18 LA segments during atrial systole. Contraction duration in 18 LA segments was measured as the time from peak of the P wave on electrocardiogram to maximum myocardial shortening in each segment. The standard deviation of contraction durations was defined as LA mechanical dispersion (LA MD). LA size was rather preserved in patients with PAF (LA volume 25 ± 10 mL/m(2)). LA MD was more pronounced in patients with recurrence of AF after RFA compared with those without recurrence and controls (38 ± 14 ms vs. 30 ± 12 ms vs. 16 ± 8 ms, both P < 0.001). LA MD was a predictor of PAF [OR 7.84 (95%CI 2.15-28.7), P < 0.01, per 10 ms increase] adjusted for age, LA volume, e', and LA function. LA function by strain was reduced in both patients with and without recurrent AF after RFA compared with controls (-14 ± 4% vs. -16 ± 3% vs. -19 ± 2%, both P < 0.05). CONCLUSION: LA MD was pronounced, and LA deformation was reduced in patients with PAF with apparently normal LV structure and function, and normal or mildly enlarged LA. LA MD may be useful as a predictor of AF recurrence after RFA.

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.