Sex differences in disease progression and arrhythmic risk in patients with arrhythmogenic cardiomyopathy.

AIMS: We aimed to assess sex-specific phenotypes and disease progression, and their relation to exercise, in arrhythmogenic cardiomyopathy (AC) patients. METHODS AND RESULTS: In this longitudinal cohort study, we included consecutive patients with AC from a referral centre. We performed echocardiography at baseline and repeatedly during follow-up. Patients' exercise dose at inclusion was expressed as metabolic equivalents of task (MET)-h/week. Ventricular arrhythmia (VA) was defined as aborted cardiac arrest, sustained ventricular tachycardia, or appropriate therapy by implantable cardioverter-defibrillator. We included 190 AC patients (45% female, 51% probands, age 41 ± 17 years). Ventricular arrhythmia had occurred at inclusion or occurred during follow-up in 85 patients (33% of females vs. 55% of males, P = 0.002). Exercise doses were higher in males compared with females [25 (interquartile range, IQR 14-51) vs. 12 (IQR 7-22) MET-h/week, P < 0.001]. Male sex was a marker of proband status [odds ratio (OR) 2.6, 95% confidence interval (CI) 1.4-5.0, P = 0.003] and a marker of VA (OR 2.6, 95% CI 1.4-5.0, P = 0.003), but not when adjusted for exercise dose and age (adjusted OR 1.8, 95% CI 0.9-3.6, P = 0.12 and 1.5, 95% CI 0.7-3.1, P = 0.30, by 5 MET-h/week increments). In all, 167 (88%) patients had ≥2 echocardiographic examinations during 6.9 (IQR 4.7-9.8) years of follow-up. We observed no sex differences in deterioration of right or left ventricular dimensions and functions. CONCLUSION: Male AC patients were more often probands and had higher prevalence of VA than female patients, but not when adjusting for exercise dose. Importantly, disease progression was similar between male and female patients.

Clinical validation of three cardiovascular magnetic resonance techniques to measure strain and torsion in patients with suspected coronary artery disease.

BACKGROUND: Several cardiovascular magnetic resonance (CMR) techniques can measure myocardial strain and torsion with high accuracy. The purpose of this study was to compare displacement encoding with stimulated echoes (DENSE), tagging and feature tracking (FT) for measuring circumferential and radial myocardial strain and myocardial torsion in order to assess myocardial function and infarct scar burden both at a global and at a segmental level. METHOD: 116 patients with a high likelihood of coronary artery disease (European SCORE > 15%) underwent CMR examination including cine images, tagging, DENSE and late gadolinium enhancement (LGE) in the short axis direction. In total, 97 patients had signs of myocardial disease and 19 had no abnormalities in terms of left ventricular (LV) wall mass index, LV ejection fraction, wall motion, LGE or a history of myocardial infarction. Thirty-four patients had myocardial infarct scar with a transmural LGE extent (transmurality) that exceeded 50% of the wall thickness in at least one segment. Global circumferential strain (GCS) and global radial strain (GRS) was analyzed using FT of cine loops, deformation of tag lines or DENSE displacement. RESULTS: DENSE and tagging both showed high sensitivity (82% and 71%) at a specificity of 80% for the detection of segments with > 50% LGE transmurality, and receiver operating characteristics (ROC) analysis showed significantly higher area under the curve-values (AUC) for DENSE (0.87) than for tagging (0.83, p < 0.001) and FT (0.66, p = 0.003). GCS correlated with global LGE when determined with DENSE (r = 0.41), tagging (r = 0.37) and FT (r = 0.15). GRS had a low but significant negative correlation with LGE; DENSE r = - 0.10, FT r = - 0.07 and tagging r = - 0.16. Torsion from DENSE and tagging had a weak correlation (- 0.20 and - 0.22 respectively) with global LGE. CONCLUSION: Circumferential strain from DENSE detected segments with > 50% scar with a higher AUC than strain determined from tagging and FT at a segmental level. GCS and torsion computed from DENSE and tagging showed similar correlation with global scar size, while when computed from FT, the correlation was lower.

Cardiac Troponin T Concentrations, Reversible Myocardial Ischemia, and Indices of Left Ventricular Remodeling in Patients with Suspected Stable Angina Pectoris: a DOPPLER-CIP Substudy.

BACKGROUND: Cardiac troponin T concentrations measured with high-sensitivity assays (hs-cTnT) provide important prognostic information for patients with stable coronary artery disease (CAD). However, whether hs-cTnT concentrations mainly reflect left ventricular (LV) remodeling or recurrent myocardial ischemia in this population is not known. METHODS: We measured hs-cTnT concentrations in 619 subjects with suspected stable CAD in a prospectively designed multicenter study. We identified associations with indices of LV remodeling, as assessed by cardiac MRI and echocardiography, and evidence of myocardial ischemia diagnosed by single positron emission computed tomography. RESULTS: Median hs-cTnT concentration was 7.8 ng/L (interquartile range, 4.8-11.6 ng/L), and 111 patients (18%) had hs-cTnT concentrations above the upper reference limit (>14 ng/L). Patients with hs-cTnT >14 ng/L had increased LV mass (144 ± 40 g vs 116 ± 34 g; P < 0.001) and volume (179 ± 80 mL vs 158 ± 44 mL; P = 0.006), lower LV ejection fraction (LVEF) (59 ± 14 vs 62 ± 11; P = 0.006) and global longitudinal strain (14.1 ± 3.4% vs 16.9 ± 3.2%; P < 0.001), and more reversible perfusion defects (P = 0.001) and reversible wall motion abnormalities (P = 0.008). Age (P = 0.009), estimated glomerular filtration rate (P = 0.01), LV mass (P = 0.003), LVEF (P = 0.03), and evidence of reversible myocardial ischemia (P = 0.004 for perfusion defects and P = 0.02 for LV wall motion) were all associated with increasing hs-cTnT concentrations in multivariate analysis. We found analogous results when using the revised US upper reference limit of 19 ng/L. CONCLUSIONS: hs-cTnT concentrations reflect both LV mass and reversible myocardial ischemia in patients with suspected stable CAD.

Strain imaging - from Scandinavian research to global deployment.

Knowledge about myocardial function is important for diagnosis, treatment and prediction of the majority of all cardiac diseases. Ejection fraction (EF) by echocardiography has been the preferred diagnostic tool for these purposes, but do have some important limitations. Strain imaging has emerged as a relatively new and important echocardiographic method that will give cardiologists incremental and additional information to EF in several important diseases affecting the myocardium. This paper will give the readers a brief overview on how and when the clinicians can use strain imaging by echocardiography in their daily practice.

A novel ECG-index for prediction of ventricular arrhythmias in patients after myocardial infarction.

BACKGROUND: Risk prediction of ventricular arrhythmias after myocardial infarction (MI) is still insufficient. Prolonged QTc is a known risk marker of mortality and ventricular arrhythmias. QTc has not achieved clinical importance in predicting arrhythmic events in patients after MI. Recent studies have displayed that the terminal part of the QT-interval, Tpeak to Tend (TpTe), may be a more promising predictor of adverse outcome. Herein, we assessed whether TpTe may serve as a predictor of ventricular arrhythmias in patients with previous MI fulfilling current implantable cardioverter-defibrillator (ICD) indications. METHODS: Seventy-six patients with previous MI eligible for ICD therapy were prospectively enrolled. ECG measurements at baseline were recorded using a 12-lead ECG with 50 mm/s paper speed. TpTe was measured from peak of the T wave to end of T wave. Events during follow up were defined as ventricular arrhythmias requiring appropriate ICD therapy, including antitachycardia pacing and shock. RESULTS: During 23 ± 19 months, arrhythmic events occurred in 36 (47%) patients. TpTe was longer in ICD patients with recorded ventricular arrhythmias compared with those without (116 ± 26 ms vs. 102 ± 20 ms; P = 0.01), whereas ejection fraction (EF) at baseline did not differ (35 ± 9% vs. 35 ± 11%; P = 0.87). TpTe was an independent predictor of ventricular arrhythmias when adjusted for age, EF and QRS duration (HR 1.16; 95% CI 1.03-1.31; P = 0.02). CONCLUSIONS: TpTe predicted malignant arrhythmias in patients after MI independently of EF. TpTe may contribute in the risk stratification of patients to identify post-MI patients disposed to malignant arrhythmias and their need of ICD therapy.

Distinguishing left ventricular hypertrophy from hypertrophic cardiomyopathy in adolescents: a longitudinal observation study.

AIMS: Echocardiographic characteristics to distinguish physiological left ventricular (LV) hypertrophy from pathology are warranted in early adolescent athletes. This study aimed to explore the phenotype, progression, and potential grey zone of LV hypertrophy during adolescence in athletes and hypertrophic cardiomyopathy (HCM) genotype-positive patients. METHODS AND RESULTS: In this longitudinal observation study, we compared seventy-six 12-year-old athletes with 55 age-matched and sex-matched HCM genotype-positive patients. Echocardiographic parameters were evaluated by using paediatric reference values (Z-scores). Hypertrophic cardiomyopathy genotype-positive patients were included if they had no or mild LV hypertrophy [maximum wall thickness <13 mm, Z-score <6 for interventricular septum diameter (ZIVSd), or posterior wall thickness]. We collected clinical data, including data on cardiac events. The mean follow-up-time was 3.2 ± 0.8 years. At baseline, LV hypertrophy was found in 28% of athletes and 21% of HCM genotype-positive patients (P = 0.42). Septum thickness values were similar (ZIVSd 1.4 ± 0.9 vs. 1.0 ± 1.3, P = 0.08) and increased only in HCM genotype-positive patients {ZIVSd progression rate -0.17 [standard error (SE) 0.05], P = 0.002 vs. 0.30 [SE 0.10], P = 0.001}. Left ventricular volume Z-scores (ZLVEDV) were greater in athletes [ZLVEDV 1.0 ± 0.6 vs. -0.1 ± 0.8, P < 0.001; ZLVEDV progression rate -0.05 (SE 0.04), P = 0.21 vs. -0.06 (SE 0.04), P = 0.12]. Cardiac arrest occurred in two HCM genotype-positive patients (ages 13 and 14), with ZIVSd 8.2-11.5. CONCLUSION: Left ventricular hypertrophy was found in a similar proportion in early adolescence but progressed only in HCM genotype-positive patients. A potential grey zone of LV hypertrophy ranged from a septum thickness Z-score of 2.0 to 3.3. Left ventricular volumes remained larger in athletes. Evaluating the progression of wall thickness and volume may help clinicians distinguish physiological LV hypertrophy from early HCM.

It is important to distinguish exercise-induced cardiac left ventricular (LV) hypertrophy from hypertrophic cardiomyopathy (HCM), because athletes with HCM may have an increased risk of sudden cardiac death. Limited data are available on this distinction in adolescent athletes. Therefore, we performed a longitudinal observation study comparing the development of LV hypertrophy during adolescence in athletes and HCM genotype­positive patients. In early adolescence, LV hypertrophy was found in a similar proportion of athletes and HCM genotype­positive patients, with a potential grey zone ranging from a septum thickness Z-score of 2.0 to 3.3. After 3 years of follow-up, LV hypertrophy had progressed only in HCM genotype­positive patients, while athletes had larger LV volumes throughout the study period.Evaluation of LV volume and septum thickness progression may assist clinicians in distinguishing exercise-induced LV hypertrophy from early HCM disease in adolescents.

Young athlete's growing heart: sex differences in cardiac adaptation to exercise training during adolescence.

BACKGROUND: Athlete's heart is a condition of exercise-induced cardiac remodelling. Adult male endurance athletes more often remodel beyond reference values. The impact of sex on remodelling through adolescence remains unclear. Paediatric reference values do not account for patient sex or exercise history. We aimed to study the effect of sex on cardiac remodelling throughout adolescence. METHODS: We recruited 76 male (M) and female (F) 12-year-old cross-country skiers in a longitudinal cohort study. Echocardiography was performed and analysed according to guidelines at age 12 (48 M, 28 F), 15 (34 M, 14 F) and 18 (23 M, 11 F). Repeated echocardiographic measurements were analysed by linear mixed model regression. RESULTS: Males displayed greater indexed left ventricular end-diastolic volumes (LV EDVi) from age 12 (M 81±7 vs F 76±7, mL/m², p≤0.01), and progressed further until follow-up at age 18 (M 2.3±9.7 vs F -3.9±4.5 ΔmL/m², p≤0.01). LV EDVi remained above adult upper reference values in both groups. Males increased LV Mass Index from age 12 to 18 (M 33±27 vs F 4±19, Δg/m², p≤0.01). Males displayed LV mass above paediatric reference values at ages 15 and 18. A subset of males (35%) and females (25%) displayed wall thickness above paediatric reference values at age 12. Cardiac function was normal. There was no sex difference in exercise hours. CONCLUSION: Sex-related differences in athlete's heart were evident from age 12, and progressed throughout adolescence. Remodelling beyond reference values was more frequent than previously reported, particularly affecting males. Age, sex and exercise history may assist clinicians in distinguishing exercise-induced remodelling from pathology in adolescents.

Right ventricular mechanical dispersion is related to malignant arrhythmias: a study of patients with arrhythmogenic right ventricular cardiomyopathy and subclinical right ventricular dysfunction.

AIMS: We evaluated if right ventricular (RV) mechanical dispersion by strain was related to ventricular arrhythmias (VT/VF) in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) and if mechanical dispersion was increased in so far asymptomatic mutation carriers. METHODS AND RESULTS: We included 69 patients, 42 had symptomatic ARVC and 27 were mutation positive asymptomatic family members. Forty healthy individuals served as controls. Myocardial strain was assessed in 6 RV and 16 left ventricular (LV) segments. Contraction duration (CD) in 6 RV and 16 LV segments were measured as the time from onset R on electrocardiogram to maximum myocardial shortening in each segment. The standard deviation of CD was defined as mechanical dispersion. Mechanical dispersion was more pronounced in ARVC patients with arrhythmias compared with asymptomatic mutation carriers and healthy individuals in RV [52(41,63) vs. 35(23,47) vs. 13(9,19)ms, P < 0.001]. Mechanical dispersion was more pronounced in asymptomatic mutation carriers compared with healthy individuals (P < 0.001). Right ventricular mechanical dispersion predicted VT/VF in a multivariate logistic regression analysis [odds ratio (OR), 1.66 (95% confidence interval (CI) 1.06-2.58), P < 0.03]. Right ventricular and LV function by strain were reduced in symptomatic ARVC patients and correlated significantly (R = 0.81, P < 0.001). Right ventricular and LV strain were reduced in asymptomatic mutation carriers compared with healthy individuals (P < 0.001). CONCLUSION: Right ventricular mechanical dispersion was pronounced in patients with ARVC with VT/VF. Right ventricular mechanical dispersion was present in asymptomatic mutation carriers and may be helpful in risk stratification. Right ventricular and LV function correlated in ARVC patients implying that ARVC is a biventricular disease.

Cardiac troponin T and NT-proBNP for detecting myocardial ischemia in suspected chronic coronary syndrome.

BACKGROUND: Elevated N-terminal pro-B-type natriuretic peptides (NT-proBNP) and cardiac troponin T (cTnT) are associated with poor outcome in patients with chronic coronary syndrome (CCS). The performance of these biomarkers in diagnosing ischemia, and their association with myocardial hypoperfusion and hypokinesis is unclear. METHODS: Patients with suspected CCS (history of angina, estimated cardiovascular risk >15% or a positive stress test) were included in the prospective, multi-center DOPPLER-CIP study. Patients underwent Single Positron Emission Computed Tomography for assessment of ischemia and NT-proBNP and cTnT were measured in venous blood samples. RESULTS: We included 430 patients (25% female) aged 64 ± 8 years. Reversible hypoperfusion and hypokinesis were present in 139 (32%) and 89 (21%), respectively. Concentrations of NT-proBNP and cTnT correlated moderately (rho = 0.50, p < 0.001). NT-proBNP and cTnT concentrations (median [IQR]) were higher in patients with versus without reversible ischemia: 150 (73-294) versus 87 (44-192) ng/L and 10 (6-13) versus 7 (4-11) ng/L, respectively (p < 0.001 for both), and the associations persisted after adjusting for possible confounders. The C-statistics to discriminate ischemia ranged from 63%-73%, were comparable for cTnT and NT-proBNP, and higher for hypokinesis than hypoperfusion, and both were superior to exercise electrocardiography and stress echocardiography. Very low concentrations (≤5 ng/L cTnT and ≤ 60 ng/L NT-proBNP) ruled out reversible hypokinesis with negative predictive value >90%. CONCLUSION: cTnT and NT-proBNP are associated with irreversible and reversible ischemia in patients with suspected CCS, particularly hypokinesis. The diagnostic performance was comparable between the biomarkers, and very low concentrations may reliably rule out ischemia.

From talented child to elite athlete: The development of cardiac morphology and function in a cohort of endurance athletes from age 12 to 18.

BACKGROUND: Adult athletes undergo cardiac adaptions in what is known as the "athlete's heart". Cardiac adaptations in young athletes have not been described in longitudinal studies but have previously been believed to be uniform in nature. METHODS: Seventy-six cross-country skiers were assessed at age 12. Forty-eight (63%) completed the first follow-up at age 15 and 36 (47%) the second follow-up at age 18. Comprehensive exercise data were collected. Echocardiography with three-dimensional measurements and cardiopulmonary exercise testing were performed at all time points. The cohort was divided into active and former endurance athletes, with an eight hours of weekly endurance exercise cut-off at age 18. RESULTS: The athletes underwent eccentric remodelling between ages 12 and 15, and concentric remodelling between ages 15 and 18. At age 18, the active endurance athletes had greater increases in inter-ventricular wall thickness (1.8 ± 1.4 Δmm vs 0.6 ± 1.0 Δmm, p < 0.05), left ventricular (LV) posterior wall thickness (1.6 ± 1.2 Δmm vs 0.8 ± 0.8 Δmm, p < 0.05), LV mass (63 ± 30 Δg vs 27 ± 21 Δg, p < 0.01), right ventricular (RV) end-diastolic area (3.4 ± 4.0 Δcm2 vs 0.6 ± 3.5Δ cm2, p < 0.05), RV end-systolic area (1.0 ± 2.3 Δcm2 vs -0.9 ± 2.0 Δcm2, p < 0.05) and left atrial volume (24 ± 21 ΔmL vs 6±10 ΔmL, p < 0.05) and had greater indexed maximal oxygen uptake (66.3 ± 7.4 mL/min/kg vs 57.1 ± 8.2 mL/min/kg, p < 0.01). There was no significant difference for LV volumes. CONCLUSION: This study finds a shift in the development of the young athlete's heart. Between ages 12 and 15, the active endurance athletes underwent eccentric remodelling. This dynamic switched to concentric remodelling between ages 15 and 18.

The cardiac impact of cisplatin-based chemotherapy in survivors of testicular cancer: a 30-year follow-up.

AIMS: Cisplatin-based chemotherapy (CBCT) is essential in the treatment of metastatic testicular cancer (TC) but has been associated with long-term risk of cardiovascular morbidity and mortality. Furthermore, cisplatin can be detected in the body decades after treatment. We aimed to evaluate the long-term impact of CBCT on cardiac function and morphology in TC survivors 30 years after treatment. METHODS AND RESULTS: TC survivors treated with CBCT (1980-94) were recruited from the longitudinal Norwegian Cancer Study in Testicular Cancer Survivors and compared with a control group matched for sex, age, smoking status, and heredity for coronary artery disease. All participants underwent laboratory tests, blood pressure measurement, and 2D and 3D echocardiography including 2D speckle-tracking strain analyses. Ninety-four TC survivors, on average 60 ± 9 years old, received a median cumulative cisplatin dose of 780 mg (IQR 600-800). Compared with controls, TC survivors more frequently used anti-hypertensive (55% vs. 24%, P < 0.001) and lipid-lowering medication (44% vs. 18%, P < 0.001). TC survivors had worse diastolic function parameters with higher E/e'-ratio (9.8 ± 3.2 vs. 7.7 ± 2.5, P < 0.001), longer mitral deceleration time (221 ± 69 vs. 196 ± 57ms, P < 0.01), and higher maximal tricuspid regurgitation velocity (25 ± 7 vs. 21 ± 4 m/s, P = 0.001). The groups did not differ in left or right ventricular systolic function, prevalence of arrhythmias, or valvular heart disease. Cumulative cisplatin dose did not correlate with cardiac parameters. CONCLUSION: No signs of overt or subclinical reduction in systolic function were identified. Long-term cardiovascular adverse effects three decades after CBCT may be limited to metabolic dysfunction and worse diastolic function in TC survivors.

The developing athlete's heart: a cohort study in young athletes transitioning through adolescence.

BACKGROUND: Athlete's heart is a term used to describe physiological changes in the hearts of athletes, but its early development has not been described in longitudinal studies. This study aims to improve our understanding of the effects of endurance training on the developing heart. METHODS: Cardiac morphology and function in 48 cross-country skiers were assessed at age 12 years (12.1 ± 0.2 years) and then again at age 15 years (15.3 ± 0.3 years). Echocardiography was performed in all subjects including two-dimensional speckle-tracking strain echocardiography and three-dimensional echocardiography. All participants underwent cardiopulmonary exercise testing at both ages 12 and 15 years to assess maximal oxygen uptake and exercise capacity. RESULTS: Thirty-one (65%) were still active endurance athletes at age 15 years and 17 (35%) were not. The active endurance athletes had greater indexed maximal oxygen uptake (62 ± 8 vs. 57 ± 6 mL/kg/min, P < 0.05) at follow-up. There were no differences in cardiac morphology at baseline. At follow-up the active endurance athletes had greater three-dimensional indexed left ventricular end-diastolic (84 ± 11 mL/m2 vs. 79 ± 10 mL/m2, P < 0.05) and end-systolic volumes (36 ± 6 mL/m2 vs. 32 ± 3 mL/m2, P < 0.05). Relative wall thickness fell in the active endurance athletes, but not in those who had quit (-0.05 ΔmL/m2 vs. 0.00 mL/m2, P = 0.01). Four active endurance athletes had relative wall thickness above the upper reference values at baseline; all had normalised at follow-up. CONCLUSION: After an initial concentric remodelling in the pre-adolescent athletes, those who continued their endurance training developed eccentric changes with chamber dilatation and little change in wall thickness. Those who ceased endurance training maintained a comparable wall thickness, but did not develop chamber dilatation.

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

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

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.

Multi-centre validation of an automatic algorithm for fast 4D myocardial segmentation in cine CMR datasets.

AIMS: Quantitative analysis of cine cardiac magnetic resonance (CMR) images for the assessment of global left ventricular morphology and function remains a routine task in clinical cardiology practice. To date, this process requires user interaction and therefore prolongs the examination (i.e. cost) and introduces observer variability. In this study, we sought to validate the feasibility, accuracy, and time efficiency of a novel framework for automatic quantification of left ventricular global function in a clinical setting. METHODS AND RESULTS: Analyses of 318 CMR studies, acquired at the enrolment of patients in a multi-centre imaging trial (DOPPLER-CIP), were performed automatically, as well as manually. For comparative purposes, intra- and inter-observer variability was also assessed in a subset of patients. The extracted morphological and functional parameters were compared between both analyses, and time efficiency was evaluated. The automatic analysis was feasible in 95% of the cases (302/318) and showed a good agreement with manually derived reference measurements, with small biases and narrow limits of agreement particularly for end-diastolic volume (-4.08 ± 8.98 mL), end-systolic volume (1.18 ± 9.74 mL), and ejection fraction (-1.53 ± 4.93%). These results were comparable with the agreement between two independent observers. A complete automatic analysis took 5.61 ± 1.22 s, which is nearly 150 times faster than manual contouring (14 ± 2 min, P < 0.05). CONCLUSION: The proposed automatic framework provides a fast, robust, and accurate quantification of relevant left ventricular clinical indices in 'real-world' cine CMR images.

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.

Acute, Exercise Dose-Dependent Impairment in Atrial Performance During an Endurance Race: 2D Ultrasound Speckle-Tracking Strain Analysis.

OBJECTIVES: This study sought to understand and characterize the acute atrial response to endurance exercise and the influence of the amount of exercise performed. BACKGROUND: Endurance exercise seems to be recognized as a risk factor for developing atrial arrhythmia. Atrial geometrical and functional remodeling may be the underlying substrate. METHODS: Echocardiography was performed in 55 healthy adults at baseline and after a 3-stage trail race: a short race (S) (14 km), n = 17; a medium race (M) (35 km), n = 21; and a long race (L) (56 km), n = 17. Analysis consisted of standard, speckle-tracking assessment of both the left ventricle (LV) and right ventricle (RV) and both the left atrium (LA) and the right atrium (RA): a-wave strain (Sa) and strain rate (Ra) as a surrogate for atrial contractile function and s-wave strain (St) and strain rate (SR) as reservoir function. RESULTS: After the race, RA reservoir function decreased in group M (Δ% SRs: -12.5) and further in group L (Δ% SRs: -15.4), with no changes in group S. RA contractile function decreased in group L (Δ% SRa: -9.3), showed no changes in group M (Δ% SRa: +0.7), and increased in group S (Δ% SRa: +14.8). A similar trend was documented in LA reservoir and contractile function but with less pronounced changes. The decrease in RA reservoir after the race correlated with the decrease in RV global longitudinal strain (GLS) (Δ% RVGLS vs. RASt and RASRs: +0.44; p < 0.05 and +0.41, respectively; p < 0.05). CONCLUSIONS: During a trail-running race, an acute exercise-dose dependent impairment in atrial function was observed, mostly in the RA, which was related to RV systolic dysfunction. The impact on atrial function of long-term endurance training might lead to atrial remodeling, favoring arrhythmia development.

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.

Brief group training of medical students in focused cardiac ultrasound may improve diagnostic accuracy of physical examination.

BACKGROUND: Physical examination and auscultation can be challenging for medical students. The aim of this study was to investigate whether a brief session of group training in focused cardiac ultrasound (FCU) with a pocket-sized device would allow medical students to improve their ability to detect clinically relevant cardiac lesions at the bedside. METHODS: Twenty-one medical students in their clinical curriculum completed 4 hours of FCU training in groups. The students examined patients referred for echocardiography with emphasis on auscultation, followed by FCU. Findings from physical examination and FCU were compared with those from standard echocardiography performed and analyzed by cardiologists. RESULTS: In total, 72 patients were included in the study, and 110 examinations were performed. With a stethoscope, sensitivity to detect clinically relevant (moderate or greater) valvular disease was 29% for mitral regurgitation, 33% for aortic regurgitation, and 67% for aortic stenosis. FCU improved sensitivity to detect mitral regurgitation (69%, P < .001). However, sensitivity to detect aortic regurgitation (43%) and aortic stenosis (70%) did not improve significantly. Specificity was ≥89% for all valvular diagnoses by both methods. For nonvalvular diagnoses, FCU's sensitivity to detect moderate or greater left ventricular dysfunction (90%) was excellent, detection of right ventricular dysfunction (79%) was good, while detection of dilated left atrium (53%), dilated right atrium (49%), pericardial effusion (40%), and dilated aortic root (25%) was less accurate. Specificity varied from 57% to 94%. CONCLUSIONS: After brief group training in FCU, medical students could detect mitral regurgitation significantly better compared with physical examination, whereas detection of aortic regurgitation and aortic stenosis did not improve. Left ventricular dysfunction was detected with high sensitivity. More extensive training is advised.

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.