Disease progression rate is a strong predictor of ventricular arrhythmias in patients with cardiac laminopathies: a primary prevention cohort study.

AIMS: Cardiac disease progression prior to first ventricular arrhythmia (VA) in LMNA genotype-positive patients is not described. METHODS AND RESULTS: We performed a primary prevention cohort study, including consecutive LMNA genotype-positive patients from our centre. Patients underwent repeated clinical, electrocardiographic, and echocardiographic examinations. Electrocardiographic and echocardiographic disease progression as a predictor of first-time VA was evaluated by generalized estimation equation analyses. Threshold values at transition to an arrhythmic phenotype were assessed by threshold regression analyses. We included 94 LMNA genotype-positive patients without previous VA (age 38 ± 15 years, 32% probands, 53% females). Nineteen (20%) patients experienced VA during 4.6 (interquartile range 2.1-7.3) years follow up, at mean age 50 ± 11 years. We analysed 536 echocardiographic and 261 electrocardiogram examinations. Individual patient disease progression was associated with VA [left ventricular ejection fraction (LVEF) odds ratio (OR) 1.4, 95% confidence interval (CI) 1.2-1.6 per 5% reduction, left ventricular end-diastolic volume index (LVEDVi) OR 1.2 (95% CI 1.1-1.3) per 5 mL/m2 increase, PR interval OR 1.2 (95% CI 1.1-1.4) per 10 ms increase]. Threshold values for transition to an arrhythmic phenotype were LVEF 44%, LVEDVi 77 mL/m2, and PR interval 280 ms. CONCLUSIONS: Incidence of first-time VA was 20% during 4.6 years follow up in LMNA genotype-positive patients. Individual patient disease progression by ECG and echocardiography were strong predictors of VA, indicating that disease progression rate may have additional value to absolute measurements when considering primary preventive ICD. Threshold values of LVEF <44%, LVEDVi >77 mL/m2, and PR interval >280 ms indicated transition to a more arrhythmogenic phenotype.

Septal contraction predicts acute haemodynamic improvement and paced QRS width reduction in cardiac resynchronization therapy.

AIMS: Three distinct septal contraction patterns typical for left bundle branch block may be assessed using echocardiography in heart failure patients scheduled for cardiac resynchronization therapy (CRT). The aim of this study was to explore the association between these septal contraction patterns and the acute haemodynamic and electrical response to biventricular pacing (BIVP) in patients undergoing CRT implantation. METHODS AND RESULTS: Thirty-eight CRT candidates underwent speckle tracking echocardiography prior to device implantation. The patients were divided into two groups based on whether their septal contraction pattern was indicative of dyssynchrony (premature septal contraction followed by various amount of stretch) or not (normally timed septal contraction with minimal stretch). CRT implantation was performed under invasive left ventricular (LV) pressure monitoring and we defined acute CRT response as ≥10% increase in LV dP/dtmax. End-diastolic pressure (EDP) and QRS width served as a diastolic and electrical parameter, respectively. LV dP/dtmax improved under BIVP (737 ± 177 mmHg/s vs. 838 ± 199 mmHg/s, P < 0.001) and 26 patients (68%) were defined as acute CRT responders. Patients with premature septal contraction (n = 27) experienced acute improvement in systolic (ΔdP/dtmax: 18.3 ± 8.9%, P < 0.001), diastolic (ΔEDP: -30.6 ± 29.9%, P < 0.001) and electrical (ΔQRS width: -23.3 ± 13.2%, P < 0.001) parameters. No improvement under BIVP was observed in patients (n = 11) with normally timed septal contraction (ΔdP/dtmax: 4.0 ± 7.8%, P = 0.12; ΔEDP: -8.8 ± 38.4%, P = 0.47 and ΔQRS width: -0.9 ± 11.4%, P = 0.79). CONCLUSION: Septal contraction patterns are an excellent predictor of acute CRT response. Only patients with premature septal contraction experienced acute systolic, diastolic, and electrical improvement under BIVP.

The role of echocardiography in management of hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is the most common non-ischemic cardiomyopathy, characterized by increased left ventricular wall thickness. Echocardiographic studies are essential for establishing the diagnosis, evaluating the extent of disease, and risk stratification. Echocardiography is also recommended in regular screening of the genotype-positive relatives. Two-dimensional, M-mode, and Doppler echocardiography are standard modalities in HCM diagnosis. Newer echocardiographic techniques as tissue Doppler, strain, and three-dimensional echocardiography are now widely used and can reveal subtle changes in the HCM patients. Echocardiography has given us a better understanding of the disease. In this review, we briefly profile the echocardiographic management of HCM in a clinical perspective.

In vivo estimation of elastic heterogeneity in an infarcted human heart.

In myocardial infarction, muscle tissue of the heart is damaged as a result of ceased or severely impaired blood flow. Survivors have an increased risk of further complications, possibly leading to heart failure. Material properties play an important role in determining post-infarction outcome. Due to spatial variation in scarring, material properties can be expected to vary throughout the tissue of a heart after an infarction. In this study we propose a data assimilation technique that can efficiently estimate heterogeneous elastic material properties in a personalized model of cardiac mechanics. The proposed data assimilation is tested on a clinical dataset consisting of regional left ventricular strains and in vivo pressures during atrial systole from a human with a myocardial infarction. Good matches to regional strains are obtained, and simulated equi-biaxial tests are carried out to demonstrate regional heterogeneities in stress-strain relationships. A synthetic data test shows a good match of estimated versus ground truth material parameter fields in the presence of no to low levels of noise. This study is the first to apply adjoint-based data assimilation to the important problem of estimating cardiac elastic heterogeneities in 3-D from medical images.

Vigorous exercise in patients with hypertrophic cardiomyopathy.

BACKGROUND: We aimed to investigate if history of vigorous exercise was associated with changes in left ventricular morphology, left ventricular function and ventricular arrhythmias (VAs) in hypertrophic cardiomyopathy genotype positive, phenotype negative (Genotype+ LVH-) and in phenotype positive (HCM LVH+). METHODS: In this cross sectional study we included 187 subjects (age 49±16years, 89(48%) female, 121(65%) HCM LVH+ and 66 (35%) Genotype+ LVH-) who answered a questionnaire on physical activity history. Exercise ≥6 metabolic equivalents was defined as vigorous. Subjects with a history of vigorous exercise ≥4h/week during ≥6years were defined as athletes. All underwent echocardiography and Holter monitoring. VAs were defined as aborted cardiac arrest, sustained or non-sustained ventricular tachycardia. RESULTS: In both Genotype+ LVH- and HCM LVH+, lifetime vigorous exercise correlated with larger left ventricular end-diastolic volume (rho 0.44 and 0.38 respectively, both p<0.001). Lifetime vigorous exercise correlated with increased left ventricular mass in Genotype+ LVH- (rho 0.28, p=0.03), but not in HCM LVH+ (p=0.53). Left ventricular systolic function was similar between athletes and non-athletes in Genotype+ LVH- and HCM LVH+. HCM LVH+ athletes had lower E/e' (p=0.03) and higher e' (p=0.02) compared to non-athletes, while this difference was not observed in Genotype+ LVH-. Lifetime vigorous exercise was similar among HCM LVH+ with and without VAs (p=0.89). CONCLUSIONS: Increased lifetime vigorous exercise was associated with larger left ventricular volumes in hypertrophic cardiomyopathy, but correlated to left ventricular mass only in Genotype+ LVH-. Vigorous exercise was associated with favorable diastolic function in HCM LVH+, and was not associated with VAs.

Data on exercise and cardiac imaging in a patient cohort with hypertrophic cardiomyopathy.

Data presented in this paper are supplementary material to our study "Vigorous exercise in patients with hypertrophic cardiomyopathy" [1]. The current article presents supplementary data on collection and analyses of exercise parameters and genetic data in the original research article.

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.

Echo-Doppler estimation of left ventricular filling pressure: results of the multicentre EACVI Euro-Filling study.

AIMS: The present Euro-Filling report aimed at comparing the diagnostic accuracy of the 2009 and 2016 echocardiographic grading algorithms for predicting invasively measured left ventricular filling pressure (LVFP). METHOD AND RESULTS: A total of 159 patients who underwent simultaneous evaluation of echo estimates of LVFP and invasive measurements of LV end-diastolic pressure (LVEDP) were enrolled at nine EACVI centres. Thirty-nine (25%) patients had a reduced LV ejection fraction (<50%), 77 (64%) were in NYHA ≥ II, and 85 (53%) had coronary artery disease. Sixty-four (40%) patients had elevated LVEDP (≥15 mmHg). Taken individually, all echocardiographic Doppler estimates of LVFP (E/A, E/e', left atrial volume, tricuspid regurgitation jet velocity) were marginally correlated with LVEDP. By using the 2016 recommendations, 65% of patients with normal non-invasive estimate of LVFP had normal LVEDP, while 79% of those with elevated non-invasive LVFP had elevated invasive LVEDP. By using 2009 recommendations, 68% of the patients with normal non-invasive LVFP had normal LVEDP, while 55% of those with elevated non-invasive LVFP had elevated LVEDP. The 2016 recommendations (sensitivity 75%, specificity 74%, positive predictive value 39%, negative predictive value 93%, AUC 0.78) identified slightly better patients with elevated invasive LVEDP (≥ 15 mmHg) as compared with the 2009 recommendations (sensitivity 43%, specificity 75%, positive predictive value 49%, negative predictive value 71%, AUC 0.68). CONCLUSION: The present Euro-Filling study demonstrates that the new 2016 recommendations for assessing LVFP non-invasively are fairly reliable and clinically useful, as well as superior to the 2009 recommendations in estimating invasive LVEDP.

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.

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.

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.