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

BACKGROUND AND AIMS: Implantable cardioverter-defibrillators (ICDs) are critical for preventing sudden cardiac death (SCD) in arrhythmogenic right ventricular cardiomyopathy (ARVC). This study aims to identify cross-continental differences in utilization of primary prevention ICDs and survival free from sustained ventricular arrhythmia (VA) in ARVC. METHODS: This was a retrospective analysis of ARVC patients without prior VA enrolled in clinical registries from 11 countries throughout Europe and North America. Patients were classified according to whether they received treatment in North America or Europe and were further stratified by baseline predicted VA risk into low- (<10%/5 years), intermediate- (10%-25%/5 years), and high-risk (>25%/5 years) groups. Differences in ICD implantation and survival free from sustained VA events (including appropriate ICD therapy) were assessed. RESULTS: One thousand ninety-eight patients were followed for a median of 5.1 years; 554 (50.5%) received a primary prevention ICD, and 286 (26.0%) experienced a first VA event. After adjusting for baseline risk factors, North Americans were more than three times as likely to receive ICDs {hazard ratio (HR) 3.1 [95% confidence interval (CI) 2.5, 3.8]} but had only mildly increased risk for incident sustained VA [HR 1.4 (95% CI 1.1, 1.8)]. North Americans without ICDs were at higher risk for incident sustained VA [HR 2.1 (95% CI 1.3, 3.4)] than Europeans. CONCLUSIONS: North American ARVC patients were substantially more likely than Europeans to receive primary prevention ICDs across all arrhythmic risk strata. A lower rate of ICD implantation in Europe was not associated with a higher rate of VA events in those without ICDs.

Lifetime exercise dose and ventricular arrhythmias in patients with mitral valve prolapse.

AIMS: Patients with mitral valve prolapse (MVP) have high risk of life-threatening ventricular arrhythmias (VAs). Data on the impact of exercise on arrhythmic risk in these patients are lacking. We explored whether lifetime exercise dose was associated with severe VA and with established risk factors in patients with MVP. Furthermore, we explored the circumstances at the VA event. METHODS AND RESULTS: In this retrospective cohort study, we included patients with MVP and assessed lifetime exercise dose as metabolic equivalents of task (MET) hours/week. Severe VA was defined as sustained ventricular tachycardia or fibrillation, aborted cardiac arrest, and appropriate shock by a primary preventive implantable cardioverter defibrillator. We included 136 MVP patients (48 years [interquartile range (IQR) 35-59], 61% female), and 17 (13%) had previous severe VA. The lifetime exercise dose did not differ in patients with and without severe VA (17 MET h/week [IQR 9-27] vs. 14 MET h/week [IQR 6-31], P = 0.34). Lifetime exercise dose > 9.6 MET h/week was a borderline significant marker for severe VA (OR 3.38, 95% CI 0.92-12.40, P = 0.07), while not when adjusted for age (OR 2.63, 95% CI 0.66-10.56, P = 0.17). Ventricular arrhythmia events occurred most frequently during wakeful rest (53%), followed by exercise (29%) and sleep (12%). CONCLUSION: We found no clear association between moderate lifetime exercise dose and severe VA in patients with MVP. We cannot exclude an upper threshold for safe levels of exercise. Further studies are needed to explore exercise and risk of severe VA.

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

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

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.

Timing of cardioverter-defibrillator implantation in patients with cardiac laminopathies-External validation of the LMNA-risk ventricular tachyarrhythmia calculator.

BACKGROUND: LMNA genotype-positive patients have high risk of experiencing life-threatening ventricular tachyarrhythmias (VTAs). The LMNA-risk VTA calculator published in 2019 has not been externally validated. OBJECTIVE: The purpose of this study was to validate the LMNA-risk VTA calculator. METHODS: We included LMNA genotype-positive patients without previous VTAs from 2 large Scandinavian centers. Patients underwent electrocardiography, 24-hour Holter monitoring, and echocardiographic examinations at baseline and repeatedly during follow-up. Validation of the LMNA-risk VTA calculator was performed using Harrell's C-statistic derived from multivariable Cox regression analysis. RESULTS: We included 118 patients (age 37 years [IQR 27-49 years]; 39 [33%] probands; 65 [55%] women; 100 [85%] with non-missense LMNA variants). Twenty-three patients (19%) experienced VTA during 6.1 years (interquartile range 3.0-9.1 years) follow-up, resulting in 3.0% (95% confidence interval 2.0%-4.5%) yearly incidence rate. Atrioventricular block and reduced left ventricular ejection fraction were independent predictors of VTAs, while nonsustained ventricular tachycardia, male sex, and non-missense LMNA variants were not. The LMNA-risk VTA calculator showed 83% sensitivity and 26% specificity for identifying patients with VTAs during the coming 5 years, and a Harrell's C-statistic of 0.85, when applying ≥7% predicted 5-year VTA risk as threshold. The sensitivity increased to 100% when reevaluating risk at the time of last consultation before VTA. The calculator overestimated arrhythmic risk in patients with mild and moderate phenotype, particularly in men. CONCLUSION: Validation of the LMNA-risk VTA calculator showed high sensitivity for subsequent VTAs, but overestimated arrhythmic risk when using ≥7% predicted 5-year risk as threshold. Frequent reevaluation of risk was necessary to maintain the sensitivity of the model.

Level 1 of Entrustable Professional Activities in adult echocardiography: a position statement from the EACVI regarding the training and competence requirements for selecting and interpreting echocardiographic examinations.

The goal of Level 1 training in echocardiography is to enable the trainee to select echocardiography appropriately for the evaluation of a specific clinical question, and then to interpret the report. It is not the goal of Level 1 training to teach how to perform the examination itself-that is the goal of higher levels of training. However, understanding the principles, indications, and findings of this crucial technique is valuable to many medical professionals including outside cardiology. This should be seen as part of a general understanding of cardiac imaging modalities. The purpose of this position statement is to define the scope and outline the general requirements for Level 1 training and competence in echocardiography. Moreover, the document aims to make a clear distinction between Level 1 competence in echocardiography and focus cardiac ultrasound (FoCUS).

The Prognostic Value of Right Atrial Strain Imaging in Patients with Precapillary Pulmonary Hypertension.

BACKGROUND: Right ventricular (RV) failure in patients with pulmonary hypertension (PH) is associated with unfavorable clinical events and a poor prognosis. Elevation of right atrial (RA) pressure is established as a marker for RV failure. However, the additive prognostic value of RA mechanical function is unclear. METHODS: The authors tested the hypothesis that RA function by strain echocardiography has prognostic usefulness by studying 165 consecutive patients with precapillary PH defined invasively: mean pulmonary artery pressure ≥ 25 mm Hg and pulmonary capillary wedge pressure < 15 mm Hg. Speckle-tracking strain analyses of the right atrium and right ventricle were performed, along with routine measures. Peak RA strain values from six segments using generic speckle-tracking software were averaged to RA peak longitudinal strain, representing RA global reservoir function. The primary end point was all-cause mortality during 5 years of follow-up. RA strain was similarly analyzed in a control group of 16 normal subjects for comparison. RESULTS: There were 151 patients with PH (mean age, 55 ± 16 years; 73% women; mean World Health Organization functional class, 2.6 ± 0.6), after 14 exclusions (three with atrial septal defects and 11 with left ventricular ejection fractions < 50%). RA strain measurement was feasible in 93% of patients and RV strain measurement in 88%. RA peak longitudinal strain was significantly reduced in patients with PH compared with control subjects, as expected (P < .001). During 5-year follow-up, 73 patients (48%) died. Patients with RA peak strain in the lowest quartile (<25%) had a significant risk for death (P = .006), even after correcting for confounding variables. RA strain was independently associated with survival in multivariate analysis (P = .039) and had additive prognostic value to RV strain (log-rank P = .01) in subgroup analysis. CONCLUSIONS: RA peak longitudinal strain had additive prognostic usefulness to other clinical measures, including RV strain, RA area, and RA pressure, in patients with PH. RA mechanical function by strain imaging has potential for clinical applications in patients with PH.

Exercise is Associated With Impaired Left Ventricular Systolic Function in Patients With Lamin A/C Genotype.

Background Lamin A/C cardiomyopathy is a malignant and highly penetrant inheritable cardiomyopathy. Competitive sports have been associated with adverse events in these patients, but data on recreational exercise are lacking. We aimed to explore associations between exercise exposure and disease severity in patients with lamin A/C genotype. Methods and Results Lamin A/C genotype positive patients answered a questionnaire on exercise habits from age 7 years until genetic diagnosis. We recorded exercise hours >3 metabolic equivalents and calculated cumulative lifetime exercise. Patients were grouped in active or sedate based on lifetime exercise hours above or below median. We performed echocardiography, 12-lead ECG, Holter monitoring, and biomarkers including NT-proBNP (N-terminal pro-B-type natriuretic peptide). We defined left ventricular ejection fraction <45% as a clinically significant impairment of left ventricular function. We included 69 patients (age 42±14 years, 41% probands, 46% women) with median lifetime exercise 4160 (interquartile range 1041-6924) hours. Active patients were more frequently probands (53% versus 29%, P=0.04), had lower left ventricular ejection fraction (43±13% versus 51±11%, P=0.006), and higher NT-proBNP (78 [interquartile range 32-219] pmol/L versus 30 [interquartile range 13-64] pmol/L, P=0.03) compared with sedate, while age did not differ (45±13 years versus 40±16 years, P=0.16). The decrease in left ventricular ejection fraction per tertile increment in lifetime exercise was 4% (95% CI -7% to -0.4%, P=0.03), adjusted for age and sex and accounting for dependence within families. Left ventricular ejection fraction <45% was observed at a younger age in active patients (log rank P=0.007). Conclusions Active lamin A/C patients had worse systolic function compared with sedate which occurred at younger age. Our findings may improve exercise recommendations in patients with lamin A/C.

Global Left Ventricular Strain at Presentation Is Associated with Subsequent Recovery in Patients with Peripartum Cardiomyopathy.

BACKGROUND: Peripartum cardiomyopathy (PPCM) is a serious complication of pregnancy associated with variable degrees of left ventricular (LV) recovery. The aim of this study was to test the hypothesis that global LV strain at presentation has prognostic value in patients with PPCM. METHODS: One hundred patients with PPCM aged 30 ± 6 years were enrolled in the multicenter Investigation in Pregnancy Associated Cardiomyopathy study along with 21 normal female control subjects. Speckle-tracking global longitudinal strain (GLS) and global circumferential strain (GCS) analysis was performed. The predefined primary combined outcome variable was death, transplantation, LV assist device implantation, or evidence of persistent LV dysfunction (LV ejection fraction [LVEF] < 50%) at 1 year. RESULTS: GLS measurement was feasible in 110 subjects: 89 of 90 patients with PPCM (99%) with echocardiographic data and all 21 control subjects. Of 84 patients (94%) with 1-year follow-up, 21 (25%) had unfavorable primary outcomes: four LV assist device placements, two deaths, and 15 patients with persistent LV dysfunction. GLS at presentation with a cutoff of 10.6% (absolute value) was specifically associated with the subsequent primary outcome with 75% sensitivity and 95% specificity. GCS at presentation with a cutoff of 10.1% was associated with the primary outcome with 78% sensitivity and 84% specificity. GLS and GCS remained significantly associated with outcomes after adjusting for LVEF (GLS odds ratio, 2.07; P < .001; GCS odds ratio, 1.37; P = .005). GLS was significantly additive to LVEF (C statistic = 0.76-0.91, net reclassification improvement = 1.32, P < .001). CONCLUSIONS: GLS and GCS in patients with PPCM at presentation were associated with subsequent clinical outcomes, including death, LV assist device implantation, and evidence of persistent LV dysfunction. Strain measures may add prognostic information over LVEF for risk stratification.

Geometry as a Confounder When Assessing Ventricular Systolic Function: Comparison Between Ejection Fraction and Strain.

BACKGROUND: Preserved left ventricular (LV) ejection fraction (EF) and reduced myocardial strain are reported in patients with hypertrophic cardiomyopathy, ischemic heart disease, diabetes mellitus, and more. OBJECTIVES: The authors performed a combined mathematical and echocardiographic study to understand the inconsistencies between EF and strains. METHODS: An analytical equation showing the relationship between EF and the 4 parameters, global longitudinal strain (GLS), global circumferential strain (GCS), wall thickness, and short-axis diameter, was derived from an elliptical LV model. The equation was validated by measuring the 4 parameters by echocardiography in 100 subjects with EF ranging from 16% to 72% and comparing model-predicted EF with measured EF. The effect of the different parameters on EF was explored in the model and compared with findings in the patients. RESULTS: Calculated EF had very good agreement with measured EF (r = 0.95). The model showed that GCS contributes more than twice as much to EF than GLS. A significant reduction of GLS could be compensated by a small increase of GCS or wall thickness or reduced diameter. The model further demonstrated how EF can be maintained in ventricles with increased wall thickness or reduced diameter, despite reductions in both longitudinal and circumferential shortening. This was consistent with similar EF in 20 control subjects and 20 hypertrophic cardiomyopathy patients with increased wall thickness and reductions in both circumferential and longitudinal shortening (all p < 0.01). CONCLUSIONS: Reduced deformation despite preserved EF can be explained through geometric factors. Due to geometric confounders, strain better reflects systolic function in patients with preserved EF.

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.

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.

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

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

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.

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

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

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.