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Global left ventricular (LV) myocardial work (MW) indices (GLVMWI) are derived from speckle tracking echocardiographic strain data in combination with non-invasive blood pressure measurements. Changes in global work index (GWI), global constructive work (GCW), global wasted work (GWW) and global work efficiency (GWE) after ST-segment elevation myocardial infarction (STEMI) have not been explored. The aim of present study was to assess the evolution of GLVMWI in STEMI patients from baseline (index infarct) to 3 months' follow-up. Three-hundred and fifty patients (265 men; mean age 61 ± 10 years) with STEMI treated with primary percutaneous coronary intervention (PCI) and guideline-based medical therapy were retrospectively evaluated. Clinical variables, conventional echocardiographic measures and GLVMWI were recorded at baseline within 48 hours post-primary PCI and 3 months' follow-up. LV ejection fraction (from 54 ± 10% to 57 ± 10%, p < 0.001), GWI (from 1449 ± 451 mm Hg% to 1953 ± 492 mm Hg%, p < 0.001), GCW (from 1624 ± 519 mm Hg% to 2228 ± 563 mm Hg%, p < 0.001) and GWE (from 93% (interquartile range (IQR) 86%-95%) to 95% (IQR 91%-96%), p < 0.001) improved significantly at 3 months' follow-up with no significant difference in GWW (from 101 mm Hg% (IQR 63-155 mm Hg%) to 96 mm Hg% (IQR 64-155 mm Hg%); p = 0.535). On multivariable linear regression analysis, lower values of troponin T at baseline, increase in systolic blood pressure and improvement in LV global longitudinal strain were independently associated with higher GWI and GCW at 3 months' follow-up. In conclusion, the evolution of GWI, GCW and GWE in STEMI patients may reflect myocardial stunning, whereas the stability in GWW may reflect permanent myocardial damage and the development of non-viable scar tissue., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Traditional parameters have limited value to estimate left ventricular filling pressure (LVFP) in orthotropic heart transplant (OHT) recipients. We hypothesized that global longitudinal strain (GLS), diastolic, and systolic strain rate (SR) would be depressed in OHT recipients with elevated LVFP and could overcome the limitations of traditional parameters. We studied consecutively OHT patients at the time of endomyocardial biopsies and retrospectively pretransplantation studies conforming to the same protocol. Comprehensive echocardiography with strain measurements was performed. Results were compared with pulmonary capillary wedge pressure (PCWP) obtained from right heart catheterization that was performed just after the echocardiography study. In all, 74 studies were performed in 50 OHT recipients. Mean PWCP was 11.8 ± 4.3 mm Hg (range: 4 to 25 mm Hg). Several parameters, but not left atrial volume index, mitral inflow velocities, annular velocities, and their ratio (E/e'), were different between studies with normal (n = 47) and elevated PCWP (n = 27). Area Under Curve for GLS (0.932*), E/e' SR (0.849*), and systolic SR (0.848*) (*p <0.0001) were more accurate than traditional parameters for predicting PCWP>12 mm Hg. GLS, systolic SR and E/e' SR remained accurate regardless of LV ejection fraction and allograft vasculopathy. Meanwhile, E/e' was accurate to predict PWCP in native failing hearts before transplantation. Changes in GLS and E/e' SR tracked accurately changes in PCWP. In conclusion, traditional indices of diastolic function perform poorly in OHT recipients, whereas GLS and E/e' SR provide reliable means of LVFP, irrespective of ejection fraction and allograft vasculopathy. These parameters also track reasonably well the changes in LVFP., Competing Interests: Declaration of Interest The authors declare that they have no known competing financial interests or personal relations that could have appeared to influence the work reported in this study., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Early-onset cardiomyopathy is a major concern for people with type 1 diabetes mellitus (DM). Studies examining myocardial deformation indices early in the disease process in people with have provided conflicting results. Accordingly, the objective was to examine left ventricular (LV) function in adolescents with type 1 DM using novel measures of cardiomyopathy, termed ventricular discoordination indices, including systolic stretch fraction (SSF), and our newly developed diastolic relaxation fraction (DRF). Adolescents with DM (n = 16) and healthy controls (n = 20) underwent cardiac MRI (CMR) tissue tracking analysis for standard volumetric and functional analysis. Segment-specific circumferential strain and strain rate indices were evaluated to calculate standard mechanical dyssynchrony and discoordination. SSF and DRF were calculated from strain rate data. There were no global or regional group differences between participants with DM and controls in standard LV strain mechanics. However, youth with DM had lower diastolic strain rate around the inferior septal and free wall region (all p <0.05) as well as higher SSF (p = 0.03) and DRF (p <0.001) compared with controls. None of the CMR indices correlated with HbA1c or diabetes duration. In conclusion, our results suggest that adolescents with DM have LV systolic and diastolic discoordination, providing early evidence of cardiomyopathy despite their young age. The presence of discoordination in the setting of normal LV size and function suggests that the proposed novel discoordination indices could serve as a more sensitive marker of cardiomyopathy than previously employed mechanical deformation indices., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Anthracycline-induced cardiotoxicity can lead to clinical and subclinical heart failure. Decrease of global longitudinal strain is a predictor for heart failure. Early detection of subclinical cardiotoxicity is crucial for timely intervention and prevention of further progression. Cardiac function of 41 survivors of childhood acute lymphoblastic leukemia (ALL) was assessed. Values of cardiac troponin T, N-terminal-pro-brain natriuretic peptide, conventional and myocardial 2D strain echocardiography were measured before (T = 0), during (T = 1, cumulative dose of 120 mg/m 2 ), shortly after (T = 2) and long after anthracycline treatment (T = 3, ≥5 years after anthracycline exposure). Cardiac function of survivors at the latest follow up was compared with 70 healthy age-matched controls. None of the survivors showed clinical signs of cardiac failure at T = 3. Strain values decreased during anthracycline treatment and an ongoing reduction was seen at the latest follow-up (T = 3) with preserved cardiac function (normal ejection fraction and shortening fraction). At T = 1, a relative reduction in longitudinal strain (≥10% compared with baseline) was observed in 38% of the survivors, which increased to 54% at T=3. ALL survivors showed significantly lower conventional and myocardial 2D strain values, especially strain rate, compared with healthy age-matched controls. At T = 3, we did not find any abnormal cardiac troponin T levels. Six percent of the survivors showed abnormal N-terminal-pro-brain natriuretic peptide levels. This prospective study showed an ongoing reduction of 2D myocardial strain and strain rate, with preserved left ventricular ejection fraction (≤10% decrease compared with baseline) in asymptomatic ALL survivors at late follow-up., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Improvement in survival in patients living with human immunodeficiency virus (PLHIV) has led to increased prevalence of cardiovascular disease. Whether HIV-associated immune dysfunction is associated with preclinical left ventricular (LV) dysfunction despite normal LV ejection fraction (LVEF) is unclear. Accordingly, we investigated the relation of immune status and LV function in PLHIV. Global longitudinal strain (GLS) analyses were performed retrospectively on all echocardiograms for PLHIV who had available HIV-1 RNA viral load, nadir, and proximal CD4 cell count data at Duke University Medical Center between 2001 and 2012. The relation between HIV-1 RNA viral load, nadir, and proximal CD4 count and GLS as a continuous dependent variable was assessed with unadjusted and adjusted linear regression. GLS was calculated for 253 PLHIV. Median GLS in our cohort was - 15.1% with interquartile range from (-16.7 to -13.6). All participants had an LVEF ≥50%. In adjusted analyses, proximal CD4 <500 cells/mm 3 and nadir CD4 <250 cells/mm 3 were significantly inversely correlated with GLS (p = 0.01 and p = 0.004, respectively). In PLHIV, patient with plasma HIV RNA <400 copies/ml at baseline had a trend toward significantly more negative values of GLS compared with those patients without viral suppression at baseline (p = 0.08). In conclusion, this study is the first to demonstrate such a high prevalence of abnormal GLS in PLHIV, and the first to identify that proximal and nadir CD4 cell count are independently associated with GLS despite normal LVEF., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Strain and synchrony are associated with clinical outcomes in children with heart diseases. Robust normative data for these values, measured by 2-dimensional speckle tracking echocardiography (2DSTE), are limited. Therefore, we aimed to derive normal ranges and z-scores of 2DSTE strain and synchrony parameters in children. Subjects were <21 years old with structurally and functionally normal hearts. High frame-rate 2-dimensional echocardiographic images were retrospectively analyzed to measure longitudinal (LS) and circumferential (CS) strain and synchrony; views used were apical 4, 2, and 3-chamber (AP 4, 2, 3) and mid-papillary short-axis (SAX-M). Synchrony measures included standard deviation of time to peak strain, maximal wall delay, and cross-correlation mean segmental delay; these were calculated without and with heart rate (HR) correction (divided by √RR). Z-score equations were created for AP4 and SAX-M strain components. n = 312 subjects (40% female) were included (age 3 days to 20.5 years). Mean strain values (%) were: AP4 -24.4 ± 3.2, AP2 -24.2 ± 3.3, AP3 -24.6 ± 3.4, SAX-M -25.8 ± 3.4. Significant differences between ages were present for all strain components (AP4 p < 0.001; AP2 p = 0.003; AP3 p = 0.014; SAX-M p = 0.01). LS components decreased with increasing age and body surface area (p < 0.001 for all); CS did not. Longitudinal, but not circumferential, synchrony parameters decreased with age; however, these were nonsignificant after HR correction. In conclusion, normal pediatric 2DSTE strain and synchrony parameters and z-scores are reported to provide a foundation for incorporation into clinical practice. LS decline with age whereas CS does not. Age-related decreases in LS synchrony were mostly nonsignificant when corrected for HR., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Cardiotoxicity from cancer therapy has become a leading cause of morbidity and mortality in cancer survivors. The most commonly used definition is cancer therapeutic related cardiac dysfunction defined as a left ventricular ejection fraction (LVEF) reduction of >10%, to a value below 50%. However, according to the recent American and European Society of Echocardiography, global longitudinal strain (GLS) is the optimal parameter for early detection of subclinical left ventricular dysfunction. The objective of this study was to evaluate the frequency of GLS reduction in patients with active cancer and its correlation to other echocardiographic parameters. Data were collected as part of the International Cardio-Oncology Registry. All patients performed at least 2 echocardiograms including GLS. We evaluated the frequency of GLS reduction (≥10% relative reduction), its correlation to LVEF reduction and whether there are other predicting echocardiographic parameters. In 64 consecutive patients, 12 (19%) had ≥10% GLS relative reduction, of which 75% had no concomitant ejection fraction reduction. There were no significant differences in the baseline cardiac risk factors (hypertension, diabetes, hyperlipidemia, or smoking). Treatment with Doxorubicin, Pertuzumab, or Ifosfamide was significantly more frequent in patients GLS reduction. No other echocardiographic parameters, including diastolic function or systolic pulmonary artery pressure were significant predictors for GLS reduction. In conclusion, our study demonstrates that GLS reduction is frequent in active cancer patients, precedes LVEF reduction and cannot be anticipated by other echocardiographic parameters. Using GLS routinely during therapy may lead to an early diagnosis of cardiotoxicity., (Copyright © 2018. Published by Elsevier Inc.)

It is unknown whether the presence of a sarcomeric mutation alone is sufficient to result in abnormal myocardial force generation, or whether additional changes in myocardial architecture (hypertrophy, disarray, and fibrosis) are required to impair systolic function. Speckle tracking echocardiography allows quantification of global strain/strain rates, twist, and dyssynchrony. In the present study we sought to further elucidate early abnormalities of myocardial mechanics in sarcomeric mutation carriers without evidence of clinical disease. Sixty genotype-positive left ventricular hypertrophy-negative (G+left ventricular hypertrophy [LVH]-) patients and 60 normal controls were studied. Velocity vector imaging was applied retrospectively to echocardiographic images to quantify global longitudinal and circumferential strain/strain rate, and rotation parameters. The G+LVH- group demonstrated both smaller left ventricular diastolic cavity dimensions (4.5 ± 0.6 cm vs 4.8 ± 0.4 cm) and a higher LVEF (66 ± 6% vs 60 ± 5%) compared with controls. An increase in circumferential subendocardial systolic strain (-30 ± 5 vs -27 ± 3%) and both systolic and diastolic subendocardial strain rate was seen in the G+LVH- group. Peak rotation angles were higher at the base and apex, with an increase in total twist (9.0 ± 3.8 vs 6.9 ± 2.9). In the control group, global and average segmental strain were similar, suggesting no/minimal dyssynchrony (global mechanical synchrony index [GMSi] 0.97-0.98). In the G+LVH- group GMSi was significantly lower (subendocardial GMSi 0.95; subepicardial GMSi 0.60), suggesting increasing subendocardial to subepicardial dyssynchrony. In conclusion, utilizing multilayer strain analysis, we demonstrate that G+LVH- subjects have enhanced subendocardial systolic strain rate and twist, as well as mechanical dyssynchrony within the left ventricular myocardium. These results demonstrate that abnormalities in myocardial mechanics precede the development of clinical hypertrophy., (Copyright © 2018. Published by Elsevier Inc.)

Little information exists on left atrial (LA) function in healthy children and in patients with congenital aortic valve stenosis (AS). We sought to determine whether patients with significant congenital AS have detectable abnormalities in LA size and function compared with matched normal controls. Retrospective chart review and analysis of 2-dimensional echocardiographic images for phasic left atrial volumes (LAVs) and longitudinal LA strain by speckle tracking in children ≥1 years of age with ≥ moderate isolated congenital AS. LAVs and LA strain in AS cases were compared with age, gender, and body surface area-matched controls (healthy children with a normal echocardiogram). Between June 2004 and October 2012, there were 36 eligible AS cases [age 13 (range 3 to 27) years; 30 males] with a median maximal Doppler gradient of 63 (range 43 to 94) mm Hg. No significant interobserver and intraobserver differences were noted in the analyses of normal subjects. Significantly higher phasic body surface area-adjusted LAVs [preatrial contraction: p = 0.01; minimal: p = 0.04] and higher LA contractile function parameters [indexed active LA stroke volume: p = 0.03; peak negative strain p = 0.04] were noted in AS cases compared with matched controls. In conclusion, compared with normal, children with congenital AS have higher preatrial contraction and minimal phasic LA volumes and higher LA contractile function., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Normal pediatric values of three-dimensional (3D) left ventricular (LV) volumes and strain are not well established; moreover, no reports exist of the stress-strain relation and the heart rate-corrected velocity of circumferential fiber shortening (VCFc) based upon 3D imaging in children. Three-dimensional LV datasets were obtained in pediatric patients (≤18 years of age) with structurally normal hearts. Ventricular volumes and strain components (longitudinal, GLS; circumferential, GCS; and 3D strain, 3DS) were analyzed using a commercial 3D speckle-tracking analysis package. LV mid-wall global average end-systolic fiber stress was calculated from 3D LV volumes. A total of 238 patients were included in the analysis with a median age of 13.1 years (range 0.4 to 17.9 years). Regression equations were derived for 3D volume parameters, permitting body surface area-based Z score calculation. Overall, 3DS values were more negative than GLS and GCS (mean ± SD = -33.8 ± 2.8; -27.8 ± 2.9; and -21.7 ± 3.1, respectively); only GLS varied significantly with age (r = 0.22; p <0.001). Both global average end-systolic fiber stress and 3D VCFc increased significantly with age (p <0.001 for both). Stress-adjusted 3DS and VCFc both varied with age (p <0.001 for both), consistent with increased contractility. In conclusion, 3D echocardiography may be used to calculate LV stress, strain, and volumes in pediatric patients with strong reproducibility. Among strain parameters, significant age-related changes were seen only in GLS. Both indexes of contractility investigated (3DS and VCFc indexed to wall stress) improved with age. Future studies of the 3D echocardiography stress-strain relation may yield new insights into maturational changes in myocardial contractility., (Copyright © 2018 Elsevier Inc. All rights reserved.)

In independent studies, abnormal global longitudinal strain (GLS) and myocardial inflammation or scar detected by 18F-fludeoxyglucose positron emission tomography (FDG-PET) are associated with poor prognosis among patients with high likelihood for cardiac sarcoidosis. However, commonly used imaging modalities have not been evaluated in the same population. Our goals were to examine the relation between GLS and FDG-PET, and to evaluate the incremental prognostic value of these imaging techniques for predicting major adverse cardiac events (MACE) in patients suspected to have cardiac sarcoidosis. We identified patients with systemic sarcoidosis who underwent an echocardiogram and FDG-PET within 60 days. Regional strain (average of base, mid, and apical segmental strains from each of 6 wall regions) was calculated and compared with regional FDG-PET findings. The associations among GLS, FDG-PET findings, and MACE (defined as death, ventricular tachycardia, heart failure hospitalization, or transplantation) were evaluated using a Cox model. Of 84 patients, 51 had abnormal FDG-PET. GLS was impaired in patients with abnormal versus normal FDG-PET (-14.2 ± 4.7% vs -17.9 ± 3.5%, p <0.01). After adjusting for clinical risk factors, both GLS and the number of segments with abnormal perfusion and metabolism on FDG-PET were associated with adverse cardiac events (p <0.01 for both). In conclusion, GLS and regional LS are impaired in patients with abnormal perfusion and metabolism detected using FDG-PET. Additionally, both GLS and abnormal FDG-PET have incremental prognostic value for predicting MACE in patients with systemic sarcoidosis., (Copyright © 2017 Elsevier Inc. All rights reserved.)

The aim of this study was to compare myocardial strain by cardiovascular magnetic resonance feature tracking (CMR-FT) to those derived from displacement encoding with stimulated echoes (DENSE) in patients with acute myocardial infarction (AMI). Twenty patients (65 pa13 years) with AMI underwent cine, DENSE, black-blood T2-weighted and late gadolinium enhancement CMR at 1.5 T. Global and segmental strain was determined by CMR-FT analysis and DENSE on matched 3 short-axis planes. Global circumferential strain by CMR-FT showed a good agreement with that by DENSE (r = 0.85, p <0.001; bias 0.02, limits of agreement -0.03 to 0.06). For segmental circumferential strain, r coefficient between CMR-FT and DENSE was 0.61 (p <0.001) with bias of 0.02, limits of agreement of -0.07 to 0.11. Regional circumferential strain determined by CMR-FT in infarct segments (-0.08 ± 0.05) was significantly altered compared with that in remote normal segments (-0.15 ± 0.05, p <0.001). CMR-FT measurement of regional and global circumferential strain showed good agreement with DENSE in patients with AMI., (Copyright © 2017 Elsevier Inc. All rights reserved.)

We evaluated the association between 2-dimensional (2D) echocardiography (echo)-determined myocardial contraction fraction (MCF) and adverse cardiovascular outcomes including incident heart failure (HF), atherosclerotic cardiovascular disease (ASCVD), and mortality. The MCF, the ratio of left ventricular (LV) stroke volume (SV) to myocardial volume (MV), is a volumetric measure of myocardial shortening that can distinguish pathologic from physiological hypertrophy. Using 2D echo-guided M-mode data from the Cardiovascular Health Study, we calculated MCF in subjects with LV ejection fraction (EF) ≥55% and used Cox models to evaluate its association with incident HF, ASCVD, and all-cause mortality after adjusting for clinical and echo parameters. We assessed whether log 2 (SV) and log 2 (MV) were consistent with the expected 1:-1 ratio used in the definition of MCF. Among 2,147 participants (age 72 ± 5 years), average MCF was 59 ± 13%. After controlling for clinical and echo variables, each 10% absolute increment in MCF was associated with lower risk of HF (hazard ratio [HR] 0.88; 95% confidence interval [CI] 0.82, 0.94), ASCVD (HR 0.90; 95% CI 0.85, 0.95), and death (HR 0.93; 95% CI 0.89, 0.97). Moreover, the MCF was still significantly associated with ASCVD and mortality, but not HF, after adjustment for percent-predicted LV mass. Significant departure from the 1:-1 ratio was not observed for ASCVD or death, but did occur for HF, driven by a stronger association for MV than SV. In conclusion, among older adults without CVD or low LV ejection fraction, 2D echo-guided M-mode-derived MCF was independently associated with lower risk of adverse cardiovascular outcomes, but this ratiometric index may not capture the full relation that is apparent when its components are modeled separately in the case of HF., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The aim of the present analysis was to evaluate the prognostic impact of different ballooning patterns in patients with Takotsubo cardiomyopathy (TTC). A total of 285 consecutive patients with TTC were included. Clinical characteristics and short- and long-term outcomes were compared between patients with typical apical ballooning (n = 204) and patients with an atypical ballooning pattern including midventricular and basal ballooning (n = 81). Patients with typical apical ballooning were significantly older (73.3 ± 10.2 vs 68.4 ± 10.3 years; p <0.01) and had a higher prevalence of diabetes mellitus (25.5% vs 12.3%; p = 0.02). The initial left ventricular (LV) ejection fraction was significantly lower in case of apical ballooning (41.5 ± 10.4% vs 46.9 ± 10.9%; p <0.01) but recovered to normal values in both groups (58.4 ± 8.0 vs 59.7 ± 7.0; p = 0.25). Although 28-day mortality did not differ significantly (p = 0.10), typical apical ballooning was associated with an increased 6-month (13.4% vs 1.3%; hazard ratio [HR] 10.81, 95% confidence interval [CI] 1.47 to 79.66; p = 0.02) and long-term mortality rates (28.9% vs 14.5%; HR 2.24, 95% CI 1.17 to 4.71; p = 0.02). A landmark analysis which included only patients who survived the first 6 months after the initial event demonstrated similar mortality rates in patients with typical (17.9%) and atypical (13.3%) ballooning (HR 1.36, 95% CI 0.67 to 2.79; p = 0.40). In conclusion, in patients with TTC, typical apical ballooning is associated with more severe LV dysfunction at acute presentation and higher mortality rates within the first 6 months after the initial event. After complete recovery of LV function, prognosis is similar in patients with typical and atypical ballooning patterns., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Blacks have higher mortality and hospitalization rates because of congestive heart failure compared with white counterparts. Differences in cardiac structure and function may contribute to the racial disparity in cardiovascular outcomes. Our aim was to compare computed tomography (CT)-derived cardiac measurements between black patients with acute chest pain and age- and gender-matched white patients. We performed a retrospective analysis under an institutional review board waiver and in Health Insurance Portability and Accountability Act compliance. We investigated patients who underwent cardiac dual-source CT for acute chest pain. Myocardial mass, left ventricular (LV) ejection fraction, LV end-systolic volume, and LV end-diastolic volume were quantified using an automated analysis algorithm. Septal wall thickness and cardiac chamber diameters were manually measured. Measurements were compared by independent t test and linear regression. The study population consisted of 300 patients (150 black-mean age 54 ± 12 years; 46% men; 150 white-mean age 55 ± 11 years; 46% men). Myocardial mass was larger for blacks compared with white (176.1 ± 58.4 vs 155.9 ± 51.7 g, p = 0.002), which remained significant after adjusting for age, gender, body mass index, and hypertension. Septal wall thickness was slightly greater (11.9 ± 2.7 vs 11.2 ± 3.1 mm, p = 0.036). The LV inner diameter was moderately larger in black patients in systole (32.3 ± 9.0 vs 30.1 ± 5.4 ml, p = 0.010) and in diastole (50.1 ± 7.8 vs 48.9 ± 5.2 ml, p = 0.137), as well as LV end-diastolic volume (134.5 ± 42.7 vs 128.2 ± 30.6 ml, p = 0.143). Ejection fraction was nonsignificantly lower in blacks (67.1 ± 13.5% vs 69.0 ± 9.6%, p = 0.169). In conclusion, CT-derived myocardial mass was larger in blacks compared with whites, whereas LV functional parameters were generally not statistically different, suggesting that LV mass might be a possible contributing factor to the higher rate of cardiac events in blacks., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Previous studies have noted reversible cardiac dysfunction during marathon races, but few data are available concerning ultradistance trail running. The aim of this study was to assess echocardiographic parameters during ultradistance trail running. We performed an observational study in 66 participants to the 80-km Ecotrail of Paris Ile de France. All subjects had echocardiographic examinations before the race and on arrival, and 28 of them underwent serial echocardiographic examinations during the race (21 and 53 km). A single experienced physician performed all echocardiographic examinations, and the same protocol was always used (conventional 2-dimensional and Doppler left ventricular parameters and longitudinal strain). All echocardiographic parameters of left ventricular (LV) systolic function were significantly decreased on arrival (p ≤0.002). A significant reduction of LV systolic function was observed in 48% of study subjects on arrival. No significant modification was observed at 21 or at 53 km, and only global longitudinal strain was significantly decreased (p = 0.0008). At arrival, mitral E/A ratio and average mitral tissue Doppler imaging e' wave were significantly decreased (p = 0.0001 and p = 0.0004, respectively), but these changes were observed from 21 km. In conclusion, ultradistance trail running can lead to abnormalities of LV systolic and diastolic functions in amateur runners. Diastolic dysfunction arises earlier than systolic dysfunction. Left ventricular systolic dysfunction occurred in 48% of the study subjects and was detected early by assessment of longitudinal strain., (Copyright © 2015 Elsevier Inc. All rights reserved.)

After repair of tetralogy of Fallot, right ventricular (RV) mass and mass:volume ratio may reflect RV remodeling and adverse outcomes. This study aimed to evaluate the relation of RV mass to functional health status and subsequent adverse RV remodeling and to determine whether RV mass measurement in systole could improve reproducibility. In 53 patients with tetralogy of Fallot (median 29 years old) who previously underwent cardiovascular magnetic resonance and completed the Short Form 36, version 2 (Optum, Eden Prairie, MN), short-axis images were analyzed for RV end-diastolic volume and diastolic and systolic mass, indexed to body surface area. The most recent subsequent cardiovascular magnetic resonance study (before pulmonary valve or conduit replacement) was evaluated for change in RV end-diastolic volume and ejection fraction. Diastolic indexed mass ≥37.3 g/m(2) (odds ratio 7.6, p = 0.02) predicted decreased general health scores. In patients with normal RV ejection fraction, indexed mass correlated with Physical Component Summary and general health scores. RV diastolic mass:volume ratio >0.2 had a strong association with subsequent increase in RV end-diastolic volume (odds ratio 26.1, p = 0.002). Systolic RV mass measurement had excellent correlation with diastolic measurement (r = 0.97, p <0.0001), but did not improve intraobserver or interobserver variability. In conclusion, RV mass relates to functional health status and adverse RV remodeling and can be measured with good reproducibility. RV mass should be routinely evaluated in this population and is best measured in diastole; further study is necessary to evaluate longitudinal changes in functional health status and RV parameters., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Insulin-like growth factor-binding protein 7 (IGFBP7) is a biomarker that has recently been associated with heart failure and cardiac hypertrophy. The aim of this study was to examine IGFBP7 relative to echocardiographic abnormalities reflecting diastolic dysfunction. One hundred twenty-four patients with ambulatory heart failure with reduced ejection fraction and baseline detailed 2-dimensional echocardiograms were followed for a mean of 10 months. IGFBP7 was measured serially at each office visit; 108 patients underwent follow-up echocardiography. Echocardiographic parameters of diastolic function were compared at baseline and over time. IGFBP7 concentrations were not linked to left ventricular size or systolic function. In contrast, those with elevated baseline IGFBP7 concentrations were more likely to have abnormalities of parameters describing diastolic function, such as higher left atrial volume index, transmitral E/A ratio, E/E' ratio, and right ventricular systolic pressure. IGFBP7 was correlated with left atrial volume index (ρ = 0.237, p = 0.008), transmitral E/A ratio (ρ = 0.304, p = 0.001), E/E' ratio (ρ = 0.257, p = 0.005), and right ventricular systolic pressure (ρ = 0.316, p = 0.001). Furthermore, each was found to be independently predictive of IGFBP7 in adjusted analysis. In subjects with baseline and final echocardiograms, more time spent with elevated IGFBP7 concentrations in serial measurement was associated with worsening diastolic function and increasing left atrial volume index or right ventricular systolic pressure. IGFBP7 concentrations were predictive of an increased risk for cardiovascular events independent of echocardiographic measures of diastolic function (p = 0.006). In conclusion, IGFBP7 is a novel prognostic biomarker for heart failure with reduced ejection fraction and shows significant links to the presence and severity of echocardiographic parameters of abnormal diastolic function., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Increased myocardial trabeculations define noncompaction cardiomyopathy (NCC). Imaging advancements have led to increasingly common identification of prominent trabeculations with unknown implications. We quantified and determined the impact of trabeculations' burden on cardiac function and stretch in a population of healthy young adults. One hundred adults aged 18 to 35 years (28±4 years, 55% women) without known cardiovascular disease were prospectively studied by cardiovascular magnetic resonance. Left ventricular (LV) volumes, segmental function, and ejection fraction (EF) and left atrial volumes were determined. Thickness and area of trabeculated (T) and dense (D) myocardium were measured for each standardized LV segment. N-terminal pro-brain natriuretic peptide (Nt-pro-BNP) was measured. Eighteen percent of the subjects had ≥1 positive traditional criteria for NCC, and 11% meet new proposed NCC cardiovascular magnetic resonance criteria. Trabeculated over dense myocardium ratio (T/D) ratios were uniformly greater at end-diastole versus end-systole (0.90±0.25 vs 0.42±0.13, p<0.0001), in women versus men (0.85±0.24 vs 0.72±0.19, p=0.006), at anterior versus nonanterior segments (1.41±0.59 vs 0.88±0.35, p<0.0001), and at apical versus nonapical segments (1.31±0.56 vs 0.87±0.38, p<0.0001). The largest T/D ratios were associated with lower LVEF (57.0±5.3 vs 62±5.5, p=0.0001) and greater Nt-pro-BNP (203±98 vs 155±103, p=0.04). Multivariable regression identified greater end-systolic T/D ratios as the strongest independent predictor of lower LVEF, beyond age and gender, left atrial or LV volumes, and Nt-pro-BNP (β=-9.9, 95% CI -15 to 4.9, p<0.001). In conclusion, healthy adults possess variable amounts of trabeculations that regularly meet criteria for NCC. Greater trabeculations are associated with decreased LV function. Apparently healthy young adults with increased trabecular burden possess evidence of mildly impaired cardiac function., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Patients with obstructive hypertrophic cardiomyopathy (HC) have various left ventricular (LV) shapes: reverse septal curvature (RSC, commonly familial), sigmoid septum (SS, common in hypertensives), and concentric hypertrophy (CH). Longitudinal (systolic and early diastolic) strain rate (SR) is sensitive in detecting regional myocardial dysfunction. We sought to determine differences in longitudinal SR of patients with obstructive HC, based on LV shapes. We studied 199 consecutive patients with HC (50% men) referred for surgical myectomy. Clinical and echocardiographic parameters were recorded. LV shapes were classified on echocardiography, using basal septal 1/3 to posterior wall ratio: RSC = ratio >1.3 (extending to mid and distal septum), SS = ratio >1.3 (extending only to basal 1/3), and concentric = ratio ≤1.3. Longitudinal systolic and early diastolic SRs were measured from apical 4- and 2-chamber views (VVI 2.0; Siemens, Erlangen). Distribution of RSC, SS, and CH was 50%, 28%, and 22%, respectively. Patients with RSC were significantly younger (47 ± 12 vs 64 ± 10 and 57 ± 11, respectively) with lower hypertension (40% vs 71% and 67%, respectively) than patients with SS or CH (both p <0.001). Patients with RSC had lower global systolic (-0.99 ± 0.3 vs -1.05 ± 0.3 and -1.17 ± 0.3) and early diastolic SR (0.95 ± 0.4 vs 0.98 ± 0.3 and 1.16 ± 0.4) versus patients with SS and CH (in 1/s, both p <0.01), despite being much younger and less hypertensive. RSC was associated with abnormal global LV systolic (beta 0.16) and early diastolic (beta -0.17) SR (both p <0.01). In conclusion, patients with HC with RCS have significantly abnormal LV mechanics, despite being younger and less hypertensive. A combination of LV mechanics and shapes could help differentiate between genetically mediated and other causes of obstructive HC., (Copyright © 2014 Elsevier Inc. All rights reserved.)

In this study, we tested the hypothesis that impaired midwall shortening predicts cardiovascular (CV) mortality in patients with type 2 diabetes mellitus (DM). In patients with DM without overt cardiac disease, systolic left ventricular (LV) function analyzed by midwall shortening may be impaired although LV ejection fraction is preserved. Impaired midwall shortening is an early independent prognosticator of adverse clinical outcome in patients with arterial hypertension. We analyzed the echocardiographic data from 360 outpatients with DM collected during the years 1990 to 2007. Patients had no history or symptoms attributable to cardiac disease. Stress-corrected midwall shortening (sc-MS) was taken as index of systolic LV function and considered impaired if <89%. The study outcome was CV mortality. At baseline, impaired sc-MS was detected in 140 patients (39%). During a mean follow-up period of 11 years, 54 patients (15%) died, 31 (8.6%) of them from CV causes. CV deaths occurred in 21 of 140 patients (15%) with impaired sc-MS and in 10 of 220 patients (4.5%) with normal sc-MS (p=0.006). Multivariate Cox regression analysis revealed that impaired sc-MS (hazard ratio 1.03, 95% confidence interval 1.01 to 1.08, p=0.039), together with lower estimated glomerular filtration rate (hazard ratio 0.96, 95% confidence interval 0.93 to 0.99, p=0.004), was independently associated with CV mortality even after adjustment for age, diabetes duration, hemoglobin A1c, left atrial diameter, and heart valve calcium. In conclusion, subclinical systolic LV dysfunction as measured by sc-MS occurs frequently in patients with DM without overt cardiac disease and independently predicts long-term CV mortality in such patients together with lower estimated glomerular filtration rate., (Copyright © 2014 Elsevier Inc. All rights reserved.)

The prognostic value of ST-segment depression on exercise electrocardiogram (eECG) in the setting of a normal wall motion response in a stress echocardiographic study is not well defined. The aim of the study was to compare outcomes among patients with normal wall motion during stress echocardiography with and without ischemic exercise electrocardiographic changes. A total of 4,233 patients underwent stress echocardiography from 2007 to 2010. The primary outcomes were a composite of all-cause mortality and myocardial infarction. Coronary revascularization was a secondary outcome. A Cox regression model was used for the primary analysis. Ischemic exercise electrocardiographic changes were defined as ST-segment depression of at least 1 mm, on at least 3 consecutive beats, and in at least 2 contiguous leads. A normal stress echocardiogram was present in 2,975 patients; of them, 2,228 (74%) had a normal eECG and 747 (26%) had ischemic changes on eECG. Patients with and without ischemic changes during exercise electrocardiography were similar in age and gender. At 4-years follow-up, 36 patients (2.8%) with a normal eECG experienced a primary end point versus 12 patients (1.9%) in the group with an ischemic exercise electrocardiographic response (p = 0.56). The rate of coronary revascularization was similar between the groups (7.0% and 5.7%, respectively, p = 0.2). There were no differences in the primary outcomes of patients with and without exercise electrocardiographic changes and normal stress echocardiogram (hazard ratio 1.33, 95% confidence interval 0.69 to 2.58). In conclusion, a normal wall motion response even in the setting of an ischemic exercise electrocardiographic response portends a benign prognosis in patients undergoing stress echocardiography., (Copyright © 2014 Elsevier Inc. All rights reserved.)

The distinction between normal right ventricular (RV) trabeculations from abnormal has been difficult. We evaluated whether RV volume and function are related to left ventricular (LV) noncompaction (NC) cardiomyopathy and clinical events. Trabeculations or possible LVNC by cardiac magnetic resonance imaging was retrospectively observed among 105 consecutive cases. We measured LV end-systolic (ES) noncompacted-to-compacted ratio, RV ejection fraction (EF), RV apical trabecular thickness, and RV end-diastolic (ED) noncompacted-to-compacted ratio. A control group of 40 subjects was also reviewed to assess the exploratory measures. Comparing those with LVES noncompacted-to-compacted ratio ≥2, those with LVES noncompacted-to-compacted ratio <2, and the normal control group, adjusted means for RV apical trabecular thickness and RVED noncompacted-to-compacted ratio were generated. Logistic regression was used to evaluate the association of composite events traditionally associated with LVNC with RVEF after adjustment for aforementioned covariates, cardiovascular risk factors, delayed enhancement, LVEF, and LVES noncompacted-to-compacted ratio. Analysis of RV morphology found greater apical trabecular thickness among those with LVES noncompacted-to-compacted ratio ≥2 compared with those with LVES noncompacted-to-compacted ratio <2 or normal control group (31 ± 5 vs 27 ± 2.6 vs 22 ± 4 mm; p = 0.03 and p = 0.003, respectively). There was no difference between the groups in relation to the RVED noncompacted-to-compacted ratio. Low RVEF and LVES noncompacted-to-compacted ratio ≥2 had significant association with clinical events in this population even after adjusting for clinical and imaging parameters (p = 0.04 and p <0.001, respectively). In conclusion, RV dysfunction in a morphologic LVNC population is strongly associated with adverse clinical events. LVNC is associated with increased trabeculations of the RV apex., (Copyright © 2014 Elsevier Inc. All rights reserved.)

We sought to determine whether depressed myocardial contraction fraction (MCF; ratio of left ventricular [LV] stroke volume to myocardial volume) predicts cardiovascular disease (CVD) events in initially healthy adults. A subset (n = 318, 60 ± 9 years old, 158 men) of the Framingham Heart Study Offspring cohort free of clinical CVD underwent volumetric cardiovascular magnetic resonance imaging in 1998 through 1999. LV ejection fraction (EF), mass, and MCF were determined. "Hard" CVD events consisted of cardiovascular death, myocardial infarction, stroke, or new heart failure. A Cox proportional hazards model adjusting for Framingham Coronary Risk Score was used to estimate hazard ratios for incident hard CVD events for gender-specific quartiles of MCF, LV mass, and LVEF. The lowest quartile of LV mass and highest quartiles of MCF and EF served as referents. Kaplan-Meier survival plots and log-rank test were used to compare event-free survival. MCF was greater in women (0.58 ± 0.13) than in men (0.52 ± 0.11, p <0.01). Nearly all participants (99%) had EF ≥0.55. During an up to 9-year follow-up (median 5.2), 31 participants (10%) developed an incident hard CVD event. Lowest-quartile MCF was 7 times more likely to develop a hard CVD (hazard ratio 7.11, p = 0.010) compared to the remaining quartiles, and increased hazards persisted even after adjustment for LV mass (hazard ratio 6.09, p = 0.020). The highest-quartile LV mass/height 2.7 had a nearly fivefold risk (hazard ratio 4.68, p = 0.016). Event-free survival was shorter in lowest-quartile MCF (p = 0.0006) but not in lowest-quartile LVEF. In conclusion, in a cohort of adults initially without clinical CVD, lowest-quartile MCF conferred an increased hazard for hard CVD events after adjustment for traditional CVD risk factors and LV mass., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Because of diastolic coupling between the left atrium and left ventricle, we hypothesized that left atrial (LA) function mirrors the diastolic function of left ventricle. The aims of this study were to assess whether LA volume parameters can be good indexes of left ventricular diastolic dysfunction. Six hundred fifty-nine patients underwent cardiac catheterization and measurements of left ventricular filling pressure (LVFP). Echocardiographic examinations including tissue Doppler and LA volumes were also assessed. Ratio of early diastolic mitral inflow velocity to early diastolic mitral annular velocity and LVFP tended to increase after progression of diastolic dysfunction. The inverse phenomenon existed in LA ejection and LA distensibility. LA distensibility was superior to LA ejection fraction and early diastolic mitral inflow velocity/early diastolic mitral annular velocity for identifying LVFP >15 mm Hg (areas under receiver operating characteristic curve 0.868, 0.834, and 0.759, respectively) and for differentiating pseudonormal from normal diastolic filling (areas under receiver operating characteristic curve 0.962, 0.907, and 0.741, respectively). Multivariate logistic regression showed that LA ejection fraction and LA distensibility were associated significantly with the presence of pseudonormal/restrictive ventricular filling. In conclusion, LA volume parameters can identify LVFP >15 mm Hg and differentiate among patterns of ventricular diastolic dysfunction. For assessing diastolic function LA parameters offer better performance than even tissue Doppler., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Left ventricular (LV) diastolic dysfunction is associated with poor outcomes after tetralogy of Fallot (TOF) repair, although its cause is not known, and its relation to right ventricular (RV) performance has never been examined. The aim of this study was to test the hypothesis that RV dilation leads to LV diastolic dysfunction after TOF repair. Patients with repaired TOF who underwent cardiac catheterization and cardiac magnetic resonance imaging within 6 months from January 2003 and April 2011 were reviewed to assess the relation of LV end-diastolic pressure (LVEDP) and indexed RV end-diastolic volume (RVEDVi). Thirty-eight patients were included at a median age of 10.1 years (range 0.6 to 54.7). There was a significant linear association between RVEDVi and LVEDP (p = 0.05). RV end-diastolic pressure (p <0.001), right pulmonary artery systolic pressure (p = 0.009), left pulmonary artery systolic pressure (p = 0.02), and total cardiopulmonary support time (p = 0.04) during TOF repair were also significantly associated with LVEDP. Compared to patients with LVEDP <12 mm Hg, those with LVEDP ≥12 mm Hg had significantly higher mean RVEDVi (135.2 ± 47.8 vs 98.6 ± 28 ml/m(2), p = 0.007) and mean RV end-diastolic pressure (11.7 ± 1.6 vs 8.5 ± 2.8 mm Hg, p = 0.0003). In conclusion, after TOF repair, LVEDP is significantly associated with RVEDVi. Furthermore, mean RVEDVi is significantly higher in patients with LVEDP ≥12 mm Hg. These findings support the theory that RV dilation may impair LV diastolic function and that LV parameters may also be important to consider in determining timing of pulmonary valve replacement., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Although Friedreich ataxia (FA) is associated with cardiomyopathy, the severity and evolution of cardiac disease is poorly understood. To identify factors predicting cardiomyopathy in FA, we assessed echocardiograms from a large heterogenous cohort and their relation to disease traits. The most recent echocardiograms from 173 subjects with FA were analyzed in a core laboratory to determine their relation to disease duration, subject age, age of onset, functional disability score, and GAA repeat length. Mean age of the cohort was 19.7 years, mean age of disease onset was 10.6 years, and mean shorter GAA length was 681 repeats. Echocardiograms collectively illustrated systolic dysfunction, diastolic dysfunction, and hypertrophy. Measurements of hypertrophy correlated moderately with each other (r = 0.39 to 0.79) but not with measurements of diastolic dysfunction (r <0.35). Diastolic measurements correlated poorly with each other, although 26% of the cohort had multiple diastolic abnormalities. The most common diastolic dysfunction classification was pseudonormalization. Classification of diastolic dysfunction was predicted by GAA repeat length but not by age or gender. Ejection fraction was below normal in 20% of the cohort. In linear regression analysis, increasing age predicted decreasing ejection fraction. Functional disability score, a measurement of neurologic ability, did not predict any echocardiographic measurements. In conclusion, hypertrophy and diastolic and systolic dysfunctions occur in FA and are substantially independent; diastolic dysfunction is the most common abnormality with most patients having an assigned diastolic dysfunction class of pseudonormalization., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Heart failure with preserved left ventricular ejection fraction (HFpEF) is implicitly attributed to diastolic dysfunction, often recognized in elderly patients with hypertension, diabetes, and renal dysfunction. In these patients, left ventricular circumferential and longitudinal shortening is often impaired despite normal ejection fraction. The aim of this prospective study was to analyze circumferential and longitudinal shortening and their relations in patients with nonischemic HFpEF. Stress-corrected midwall shortening (sc-MS) and mitral annular peak systolic velocity (S') were measured in 60 patients (mean age 73 ± 13 years) with chronic nonischemic HFpEF in stable New York Heart Association functional class II or III and compared to the values in 120 healthy controls and 120 patients with hypertension without HFpEF. Sc-MS was classified as low if <89% and S' as low if <8.5 cm/s (the 10th-percentile values of healthy controls). Isolated low sc-MS was detected in 46% of patients with HFpEF, 27% of patients with hypertension, and 2% of controls; isolated low S' was detected in 11% of patients with HFpEF, 7% of patients with hypertension, and 5% of controls; and combined low sc-MS and low S' was detected in 26% of patients with HFpEF, 9% of patients with hypertension, and 5% of controls (HFpEF vs others, all p values <0.001). Thus, any alteration of systolic function was found in 83% of patients with HFpEF. The relation between sc-MS and S' was nonlinear (cubic). Changes in S' within normal values corresponded to negligible variations in sc-MS, whereas the progressive decrease below 8.5 cm/s was associated with substantial decrease in sc-MS. In conclusion, circumferential and/or longitudinal systolic dysfunction is present in most patients with HFpEF. Circumferential shortening normalized by wall stress identifies more patients with concealed left ventricular systolic dysfunction than longitudinal shortening., (Copyright © 2012 Elsevier Inc. All rights reserved.)

The current exercise tolerance test (ETT) criteria predominantly assess changes in ST-segment deviation (i.e., a systolic component of the cardiac cycle). Because diastolic dysfunction precedes that of systolic dysfunction during myocardial ischemia and most coronary flow is diastolic, the addition of electrocardiographic markers of diastolic time might improve the ETT sensitivity and specificity for detecting significant coronary artery disease. Among consecutive patients who had an ETT and subsequently underwent coronary angiography, we evaluated the diastolic time by assessing the TP and TQ segments and TP/RR and TQ/RR ratios in each ETT stage. Coronary artery disease was defined angiographically as significant (≥70% lumen occlusion), intermediate (>50% but <70% lumen occlusion), or nonsignificant (≤50% lumen occlusion). Of the 48 study patients, hypertension and hyperlipidemia appeared highly prevalent. TP, TQ, TP/RR, and TQ/RR correlated significantly with RR and changed with each ETT stage. Although TP and TQ were not significantly associated with significant coronary artery disease, TP/RR and TQ/RR proved to be, particularly beyond stage 2. When TQ/RR of ≤0.39 and TP/RR of ≤0.13 were used, their individual sensitivities and specificities were reasonably comparable to that of traditional ETT criteria (79% sensitivity and 44% specificity at our institution). Adding TQ/RR of ≤0.39 and/or TP/RR of ≤0.13 to existing ETT criteria improved its sensitivity to 100% and specificity to 86%. In conclusion, the addition of diastolic time indexes of TP/RR and TQ/RR significantly improved the overall ETT diagnostic value above the guideline-oriented, perhaps "traditional," criteria for the diagnosis of myocardial ischemia. Such parameters should be widely investigated further for clinical accuracy and compatibility., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Although stress gated technetium-99m single-photon emission computed tomographic (SPECT) myocardial perfusion imaging (MPI) is useful in differentiating ischemic from nonischemic cardiomyopathy, its prognostic usefulness in this patient population is not well understood. Consecutive unique patients with suspected coronary artery disease who, for clinical indications, underwent technetium-99m rest and stress MPI demonstrating ejection fractions ≤40% by gated SPECT imaging were retrospectively identified. In addition to prescan variables, previously defined cutoffs for gated SPECT parameters using visual and standard 17-segment semiquantitative scoring were applied and related to the occurrence of cardiac death up to 5 years after MPI. Of the 475 patients fulfilling criteria for study inclusion, follow-up was complete in 444 (93%) over 3.7 ± 1.6 years. Of 393 patients without subsequent early (≤60 days) coronary revascularization, cardiac death occurred in 64 (16%). The summed stress score, an MPI measure of the extent and severity of coronary artery disease that also accounts for the ischemic burden, was the gated SPECT parameter most related to cardiac death with Kaplan-Meier 5-year cardiac death-free survival of 85.6% and 67.3% in patients with summed stress scores ≤8 and >8, respectively (p <0.001). In multivariate Cox regression analysis, a summed stress score >8 independently contributed to cardiac death (adjusted hazard ratio 2.20, 95% confidence interval 1.34 to 3.61), and its addition to the model significantly increased the global chi-square value over prescan variables (from 32.46 to 41.67, p = 0.002). In conclusion, stress MPI data from gated technetium-99m SPECT scans are useful for the prediction of cardiac death in patients with moderate to severe left ventricular systolic dysfunction in whom there is suspicion of underlying coronary artery disease., (Copyright © 2012 Elsevier Inc. All rights reserved.)

The tricuspid annular peak systolic velocity (TAPSV) is an echocardiographic measurement assessing right ventricular systolic function in children and adults. We determined the growth-related changes of the TAPSV to establish the references values for the entire pediatric age group. A prospective study was conducted of a group of 860 healthy pediatric patients (age 1 day to 18 years; body surface area [BSA] 0.14 to 2.30 m(2)). We determined the effects of age, gender, and BSA on the TAPSV values. Stepwise linear multiple regression analysis was used to estimate the TAPSV from the age, BSA, and gender. A correlation of normal TAPSV with normal tricuspid annular plane systolic excursion values was performed. The TAPSV ranged from a mean of 7.2 cm/s (z score ± 2: 4.8 to 9.5 cm/s) in the newborn to 14.3 cm/s (z score ± 2: 10.6 to 18.6 cm/s) in the 18-year-old adolescent. The TAPSV values showed a positive correlation with age and BSA, with a nonlinear course. No significant difference was found in the TAPSV values according to gender. A significant correlation was found between the TAPSV and tricuspid annular plane systolic excursion values in our pediatric population. In conclusion, the z scores of the TAPSV values were calculated, and percentile charts were established to serve as reference data for patients with congenital heart disease., (Copyright © 2012 Elsevier Inc. All rights reserved.)

The purpose of the present study was to evaluate the role of left ventricular global afterload and various echocardiographic parameters of systolic function in a prospective cohort of 52 asymptomatic patients with severe aortic stenosis (indexed aortic valve area 0.4 ± 0.1 cm²/m²) and normal left ventricular ejection fraction (61 ± 5%). Using 2-dimensional speckle tracking echocardiography, myocardial strain, rotation, and twist were evaluated. The valvuloarterial impedance (Zva) was calculated as a measure of left ventricular global afterload. The predefined end points were the occurrence of symptoms (dyspnea, angina, syncope), aortic valve replacement, and death. At study entry, all patients had decreased longitudinal strain (LS) (-15 ± 4%) and increased circumferential strain (-22 ± 5%), twist (24 ± 7°), and Zva (5.8 ± 2 mm Hg/ml/m²). Increased Zva was closely associated with the circumferential strain increase (r = 0.59, p = 0.02) and LS decrease (r = -0.56, p = 0.016). In contrast, no relation was found between myocardial function and transaortic gradients. During follow-up (11 ± 7.5 months), on univariate Cox regression analysis, the predictors of events were the left ventricular ejection fraction (p = 0.02), mass index (p = 0.01), LS (p < 0.0001), radial strain (p = 0.04), and Zva (p = 0.0002). On multivariate Cox regression analysis, only the global LS (p = 0.03) and Zva (p = 0.03) were independently associated with the combined end point. Using receiver operating characteristic curve analysis, a LS of ≤-18% (sensitivity 96%, specificity 73%) and a Zva of ≥ 4.7 mm Hg/ml/m² (sensitivity 100%, specificity 91%) were identified as the best cutoff values to be associated with events. In conclusion, in asymptomatic patients with severe aortic stenosis, the degree of global afterload and its consequences on longitudinal function might play a role in clinical practice., (Copyright © 2011 Elsevier Inc. All rights reserved.)

In the present study, we hypothesized that hypoadiponectinemia and hyperleptinemia might be associated with left ventricular (LV) diastolic dysfunction. To test the hypothesis, we examined the relation of the plasma levels of adiponectin and leptin with the indexes of LV diastolic and systolic function (relaxation time constant, end-diastolic pressure, and ejection fraction) in 193 consecutive patients undergoing cardiac catheterization for coronary artery disease (age 69 ± 9 years, 74% men; ejection fraction 68.4 ± 9.9%). Regardless of gender, the adiponectin levels correlated negatively with the relaxation time constant and end-diastolic pressure, and the correlations remained significant after adjustment for potential confounders, including age, body mass index, heart rate, blood pressure, and coronary artery disease severity. Adiponectin levels did not significantly correlate with the ejection fraction in either men or women. The leptin levels did not significantly correlate with the indexes of LV diastolic or systolic function in either men or women. In conclusion, we found that decreased adiponectin levels were associated with LV diastolic dysfunction in patients with known or suspected coronary artery disease., (Copyright © 2011 Elsevier Inc. All rights reserved.)

The effects of aging and of sustained athletic activity on the heart in men aged >50 years are unknown. The aim of this study was to assess the adaptation of the heart in athletic and sedentary men aged <35 and ≥50 years. Echocardiograms recorded at rest and during submaximal exercise were analyzed in 59 athletic seniors (S(ATH) group) and 16 sedentary seniors (S(SED) group) (age ≥50 years) and in 18 athletic youth (Y(ATH) group) and 27 sedentary youth (Y(SED) group) (age <35 years). All subjects were healthy. The reproducibility of measurements was examined, and the echocardiographic characteristics were compared among the study groups. No differences were found in baseline characteristics between the Y(ATH) and Y(SED) groups and between the S(ATH) and S(SED) groups, except for their exercise routines, consisting of >8 hours of bicycling per week in the athletic groups. Left ventricular mass was greater in the Y(ATH) than in the S(ATH) group (p <0.01) and greater in the S(ATH) than in the S(SED) group (p <0.001). Likewise, left ventricular volumes were greater in the athletic than in the sedentary groups (p <0.05), although they were smaller in the seniors than in youth (p <0.01). Left ventricular stroke volume was greater in the athletic than in the sedentary groups (p <0.001); global longitudinal strain during exercise was -20.0 ± 2.4% in the S(ATH) group and -22.1 ± 2.1% in the Y(ATH) group, compared to -19.2 ± 3.4% in the S(SED) group and -20.2 ± 2.4% in the Y(SED) group (p <0.05, athletic vs sedentary). The e' velocities recorded at the septal and lateral mitral annulus were higher at rest and during exercise (p <0.01) in the youth than in the senior groups. In conclusion, systolic and diastolic myocardial adaptation to regular exercise was significantly more prominent in young than in senior volunteers., (Copyright © 2011 Elsevier Inc. All rights reserved.)

The aim of this study was to determine whether assessment of global longitudinal strain (GLS) before revascularization could predict adverse cardiac events after ST-segment elevation myocardial infarction (STEMI). In addition, the relation between GLS and cardiac biomarkers was investigated. From July 2006 through December 2009, 98 patients with first STEMI underwent conventional and speckle tracking echocardiography at initial presentation and 3 days after primary coronary intervention. Patients were divided into 3 groups according to percent changes of GLS compared to baseline GLS values: group 1, improved GLS >10%; group 2, unchanged GLS from -10% to 10%; and group 3, decreased GLS <-10%. Subsequent complications including all-cause mortality and readmission because of congestive heart failure during a 6-month period of follow-up were prospectively evaluated. After coronary intervention, GLS was improved in 29 patients (30%, group 1), unchanged in 55 patients (56%, group 2), and worsened in 14 patients (14%, group 3). Complications developed in 7 patients (group 1, n = 0, 0%; group 2, n = 2, 28%; group 3, n = 5, 72%, p <0.01). Multivariate Cox analysis showed an independent association of GLS before and after coronary intervention with subsequent complications. Significant correlations were observed between GLS and cardiac biomarkers. In conclusion, GLS assessment before coronary intervention was a good predictor of complications in patients with STEMI comparable to predictions using GLS after intervention at 6-month follow-up., (Copyright © 2011 Elsevier Inc. All rights reserved.)

We studied the spatial relations among hyperemic myocardial blood flow (hMBF), contractile function, and morphologic tissue alterations in 19 patients with hypertrophic cardiomyopathy (HC). All patients were studied with oxygen-15 water positron emission tomography during rest and adenosine administration to assess myocardial perfusion. Cardiovascular magnetic resonance was performed to derive delayed contrast-enhanced images and to calculate contractile function (E(cc)) with tissue tagging. Eleven healthy subjects underwent similar positron emission tomographic and cardiovascular magnetic resonance scanning protocols and served as a control group. In the HC group, hMBF averaged 2.46 ± 0.91 ml/min/g and mean E(cc) was -14.7 ± 3.4%, which were decreased compared to the control group (3.97 ± 1.48 ml/min/g and -17.7 ± 3.2%, respectively, p <0.001 for the 2 comparisons). Delayed contrast enhancement (DCE) was present only in patients with HC, averaging 6.2 ± 10.3% of left ventricular mass. In the HC group, E(cc) and DCE in the septum (-13.7 ± 3.6% and 10.2 ± 13.6%) significantly differed from the lateral wall (-16.0 ± 2.8% and 2.4 ± 5.9%, p <0.001 for the 2 comparisons). In general, hMBF and E(cc) were decreased in segments displaying DCE compared to nonenhanced segments (p <0.001 for the comparisons). In the HC group, univariate analysis revealed relations of hMBF to E(cc) (r = -0.45, p <0.001) and DCE (r = -0.31, p <0.001). Multivariate analysis revealed that E(cc) was independently related to hMBF (beta -0.37, p <0.001) and DCE (beta 0.28, p <0.001). In conclusion, in HC hMBF is impaired and related to contractile function independent from presence of DCE. When present, DCE reflected a progressed disease state as characterized by an increased perfusion deficit and contractile dysfunction., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Decreased left ventricular (LV) longitudinal strain and increased circumferential LV strain have been demonstrated in patients with severe aortic stenosis (AS) and normal LV ejection fraction (LVEF). Biplane myocardial mechanics normalize after aortic valve replacement (AVR). This study objective was to examine LV mechanics before and soon after AVR in patients with AS and LV systolic dysfunction. Paired echocardiographic studies before and soon (7 ± 3 days) after AVR were analyzed in 64 patients with severe AS: 32 with normal LVEF (≥ 50%), 16 with mild to moderate LV dysfunction (LVEF <36% to 50%), and 16 with severe LV dysfunction (LVEF ≤ 35%). Longitudinal myocardial function was assessed from 3 apical views (average of 18 segments) and circumferential function was assessed at mid-LV and apical levels (average of 6 segments per view). Strain, strain rate, and mid-LV and apical rotations were measured using 2-dimensional velocity vector imaging. Before AVR (1) longitudinal strain was low in all patients and correlated with LVEF (ρ = 0.74, p <0.001), (2) mid-LV circumferential strain was supranormal in patients with normal LVEF and low in patients with low LVEF (ρ = 0.88, p <0.001), and (3) apical rotation was highest in patients with mild to moderate LV dysfunction. After AVR, LVEF increased in patients with LV dysfunction and myocardial mechanics partly normalized. In conclusion, compensatory mechanisms (high circumferential strain in patients with preserved LVEF and increased apical rotation in patients with mild to moderate LV dysfunction) were observed in patients with severe AS. Compensatory mechanics were lost in patients with severe LV dysfunction. AVR partly reversed these changes in patients with LV dysfunction., (Copyright © 2011 Elsevier Inc. All rights reserved.)

The influence of volume overload on ventricular performance has been previously investigated but primarily with respect to the duration of overload. The aim of the present study was to elucidate whether the magnitude of the preoperative volume overload, represented by the ventricular volume, has any effect on ventricular performance long after the Fontan operation in patients with tricuspid atresia. We evaluated consecutive changes in hemodynamic catheterization data obtained at 1, 5, and 10 years after primary Fontan repair. The variables were compared between patients with larger (n = 20) and smaller (n = 21) ventricles (preoperative end-diastolic volume [percentage of predicted] 262 ± 33%, maximum 320% vs 182 ± 22%, minimum 133%, respectively). In a subgroup of patients (n = 33) who underwent symptom-limited exercise at 10.7 ± 3.0 postoperative years, the peak oxygen uptake was measured, and the potential predictors were interrogated. The difference in ventricular contractility between the groups tended to increase with time, with those with a larger ventricle showing poorer contraction, irrespective of whether it was assessed in a load-dependent (ejection fraction) or load-independent (end-systolic elastance) manner. The differences in these variables reached statistical significance at 10 years (p = 0.028 and p = 0.032). Multivariate analysis indicated a larger ventricle was an independent risk factor of poorer aerobic capacity (p = 0.047). In conclusion, ventricular performance was less preserved in those with a larger ventricle, which might result in suboptimal aerobic capacity. Our findings suggest not only early unloading, but also avoidance of excessive volume overload is of importance to minimize the deleterious effect of volume overload on an inherently susceptible ventricle., (Copyright © 2011. Published by Elsevier Inc.)

The present study aimed to determine the predictors of patient-reported quality of life and restrictive right ventricular (RV) physiology in adolescents and adults with repaired tetralogy of Fallot. A total of 62 patients (median age 28.5 years, range 14 to 69) undergoing cardiovascular magnetic resonance imaging completed the Short Form 36-item questionnaire, version 2, a validated quality of life assessment. RV inflow curves were generated from the sum of tricuspid inflow and pulmonary insufficiency. The patient-reported quality of life was comparable to population norms. Patients repaired after 1 year of age showed a strong trend toward a greater likelihood of physical component summary age-adjusted z-score ≤-1 (odds ratio 7.50, 95% confidence interval 0.90 to 62.3, p = 0.06). Patients with a RV ejection fraction of <45% reported decreased physical component summary (p = 0.02) and physical functioning (p = 0.02) scores. The RV end-diastolic volume, pulmonary regurgitation, and diastolic indexes did not predict the quality of life. The indexed RV end-diastolic volume was related to diastolic abnormalities, correlating with a greater peak early filling rate (r = 0.71, p <0.0001), ratio of peak early to atrial filling rates (r = 0.45, p = 0.006), and showing a strong trend with the end-diastolic forward flow in the pulmonary trunk (odds ratio 2.67 for moderate dilation and 3.50 for severe dilation, p = 0.06). Patients who underwent repair before 1 year old were more likely to have end-diastolic forward flow (15 of 17 vs 25 of 42, p = 0.03). In conclusion, the RV ejection fraction and age of repair were the best predictors of quality of life in this population, in whom end-diastolic forward flow and associated diastolic parameters appeared to reflect an overdistended ventricle, which might suggest a role for early pulmonary valve replacement., (Copyright © 2010 Elsevier Inc. All rights reserved.)

The aim of this study was to determine the impact of aortic stenosis (AS) on the different components of left atrial (LA) function. The study consisted of a total of 52 consecutive patients with severe AS (aortic valve area < 1 cm(2)) and 20 normal subjects matched for gender, heart rate, body surface area, and baseline systolic blood pressure. Phasic LA longitudinal function was assessed using tissue Doppler imaging. LA peak systolic (reservoir function), early diastolic (conduit function), and late diastolic (active function) strain rates were measured. During late diastole, LA peak strain (active function) was also measured. Mitral annular systolic, early diastolic (Ea), and late diastolic (Aa) velocities were also measured. Compared with controls, all strain values were significantly reduced in patients with AS. By multivariate regression analysis, mitral E-wave deceleration time (p = 0.033) and E/Ea ratio (p = 0.02, R(2) = 0.43) emerged as independently associated with LA peak systolic strain rate. Ea was the sole determinant of LA early diastolic strain rate (p < 0.0001, R(2) = 0.42), whereas LA late diastolic strain rate was independently related to aortic valve area (p = 0.031) and Aa (p = 0.022, R(2) = 0.51). In conclusion, in patients with severe AS, the 3 components of LA function are reduced. LA reservoir dysfunction is related to left ventricular filling pressures, whereas LA conduit dysfunction depends on left ventricular relaxation. Active LA dysfunction is related to the severity of AS and late left ventricular diastolic function., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Cardiac resynchronization therapy (CRT) is considered a class I indication in treatment of patients with New York Heart Association (NYHA) functional class III and IV heart failure. However, only small numbers of patients in large clinical trials have been in NYHA functional class IV. Therefore, little is known about the effects of CRT in this group. Therefore, we evaluated the effects of CRT in patients with NYHA functional class IV heart failure. Of all patients referred for CRT implantation, 61 patients with symptoms according to NYHA functional class IV were included. All patients were evaluated before implantation and at 6-month follow-up for clinical changes according to the clinical composite score and changes in left ventricular (LV) volumes and function. In addition, survival was evaluated during long-term follow-up. At 6-month follow-up, 9 patients (15%) had died and 2 patients (3%) were admitted for worsening heart failure. The remaining 39 patients (64%) showed improvement according to the clinical composite score. Decreases in LV end-systolic volume (from 167 ± 88 to 147 ± 93 ml, p = 0.009) and LV end-diastolic volume (from 211 ± 100 to 199 ± 113 ml, p = 0.135) were observed, as was a significant increase in LV ejection fraction (from 22 ± 8% to 28 ± 9%, p <0.001). During a mean follow-up of 30 ± 26 months, 36 patients (59%) died, 27 (75%) from worsening heart failure. Respective 1- and 2-year mortality rates were 25% and 38%. In conclusion, CRT decreases LV volumes and improves cardiac function in patients with NYHA functional class IV heart failure. Nevertheless, (heart failure) mortality remains high in these patients., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Despite their potential as a sensitive measure of ventricular performance, tissue Doppler velocities vary with normal aging. This is inconvenient for nonspecialists to interpret and makes it difficult to use as an entry criterion for clinical studies. The age-adjusted tissue Doppler Z-scores might avoid these disadvantages and be more discriminant for myocardial impairment than the raw velocities. We conducted a meta-regression of studies reporting age-specific normal tissue Doppler velocities to determine a consensus formula for Z-scores (8 studies, 1,867 patients) that we then tested in an independent study at our institution. We next compared the Z-scores head-to-head with the raw velocities for their ability to distinguish a fresh set of 81 healthy subjects from groups in whom subtle ventricular dysfunction might be expected, including 50 patients with dilated cardiomyopathy, 50 with aortic regurgitation, and 50 with mitral regurgitation. The discriminant capacity, assessed by the area under the receiver operating characteristic curves, was higher for the Z-scores than for the raw velocities in each patient group. At the septal angle of the mitral annulus: dilated cardiomyopathy 0.95 versus 0.92 (p = 0.03), aortic regurgitation 0.83 versus 0.78 (p = 0.02), mitral regurgitation 0.85 versus 0.81 (p = 0.04). At the lateral angle: dilated cardiomyopathy 0.94 versus 0.88 (p = 0.005), aortic regurgitation 0.92 versus 0.83 (p = 0.001), mitral regurgitation 0.87 versus 0.85 (p = 0.31). In conclusion, the Z-scores of the tissue Doppler velocities were better than the raw velocities at detecting myocardial impairment in valvular or heart muscle disease. The calculation needs only the raw velocity and patient age. Tissue Doppler Z-scores could be used to create a novel, more sensitive, definition of ventricular dysfunction and might make it easier for nonspecialists to interpret the reports., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Decisions regarding cardiac transplantation listing are difficult in patients with heart failure who have relatively discordant peak exercise oxygen consumption (Vo(2)) and cardiac index (CI) values. One hundred five patients with heart failure who underwent cardiopulmonary exercise testing and right-sided cardiac catheterization for transplantation evaluation were studied. Patients were divided into 4 groups on the basis of peak Vo(2) and CI: group 1, Vo(2) > or = 12 ml/min/kg, CI > or = 1.8 L/min/m(2) (n = 30); group 2, Vo(2) > or = 12 ml/min/kg, CI <1.8, L/min/m(2) (n = 27); group 3, Vo(2) <12 ml/min/kg, CI > or = 1.8 L/min/m(2) (n = 25); and group 4, Vo(2) <12 ml/min/kg, CI <1.8 L/min/m(2) (n = 23). Groups were compared for event-free (death or ventricular assist device) survival. The overall CI was 1.9 + or - 0.4 L/min/m(2) and peak Vo(2) was 12.4 + or - 2.8 ml/min/kg; values in the 4 groups were as follows: group 1, peak Vo(2) 14.7 + or - 2.1 ml/min/kg, CI 2.2 + or - 0.3 L/min/m(2); group 2, peak VO(2) 14.2 + or - 1.3 ml/min/kg, CI 1.5 + or - 0.2 L/min/m(2); group 3, peak Vo(2) 10.2 + or - 1.3 ml/min/kg, CI 2.1 + or - 0.3 L/min/m(2); and group 4, peak Vo(2) 9.7 + or - 2.0 ml/min/kg, CI 1.6 + or - 0.2 L/min/m(2). After a median follow-up period of 3.7 years, 28 patients (26.0%) had events. Event-free survival was 96%, 95%, 96%, and 79% for 6 months (p = 0.04); 88%, 81%, 90%, and 73% for 12 months (p = 0.09); 88%, 73%, 85%, and 65% for 18 months (p = 0.11); and 83%, 73%, 79%, and 53% for 24 months (p = 0.06) for groups 1 to 4, respectively. Median survival was 5.1, 3.0, 3.9, and 2.6 years, respectively, in groups 1 to 4 (p = 0.052). In conclusion, almost half the patients had relatively discordant peak Vo(2) and CI measurements. Patients with lower peak Vo(2) values but relatively preserved CI values had survival comparable to post-transplantation survival, whereas those with low CI but preserved Vo(2) had a lower survival rate. These results suggest that the former group may be safely monitored on medical therapy, whereas the latter may benefit from early listing., (Copyright 2010 Elsevier Inc. All rights reserved.)

The optimal timing of coronary angiography in patients with non-ST elevation (NSTE) acute coronary syndromes (ACS) is debated. American Heart Association and American College of Cardiology guidelines recommend an early invasive strategy <12 to 48 hours after the onset of symptoms. The objective of the present study was to determine possible changes in myocardial function in patients with NSTE ACS awaiting coronary angiography. One hundred two patients with suspected NSTE ACS were enrolled, including 56 with NSTE myocardial infarctions (NSTEMIs), 23 with unstable angina pectoris, and 23 with noncoronary chest pain. Global and regional myocardial function was measured as longitudinal and circumferential strain using speckle-tracking echocardiography. Measurements were performed at admission and immediately before coronary angiography (30 + or - 16 hours after admission). In patients with NSTEMIs, there was deterioration in longitudinal global strain from -16.1 + or - 2.6% at admission to -15.0 + or - 2.6% before coronary angiography (p <0.001). This was due to deterioration in longitudinal strain in the territory supplied by the infarct-related artery from -14.2 + or - 4.2% to -12.0 + or - 4.1% (p <0.001). Patients with NSTEMIs due to acute coronary occlusion underwent prominent worsening in longitudinal and circumferential strains (-15.7 + or - 2.9% to -13.9 + or - 3.0%, p = 0.001, and -16.7 + or - 4.0% to -15.0 + or - 3.9%, p = 0.01, respectively) compared to patients with NSTEMIs without occlusions. There were no changes in strain in patients with unstable angina pectoris or noncoronary chest pain. In patients with NSTEMIs without acute coronary occlusions, myocardial function improved after revascularization, whereas patients with acute occlusions demonstrated no improvement. In conclusion, myocardial function deteriorates in patients with NSTEMIs awaiting coronary angiography. Patients with acute coronary occlusions have the most prominent deterioration, and this subgroup shows no recovery of function after revascularization., (Copyright 2010 Elsevier Inc. All rights reserved.)

In patients with ST-segment elevation myocardial infarction treated with fibrinolytics, electrocardiogram-derived measures of ST-segment recovery guide therapy decisions and predict infarct size. The comprehension of these relationships in patients undergoing mechanical reperfusion is limited. We studied 144 patients treated with primary percutaneous coronary intervention. We aimed to define the association between infarct size as determined by cardiac magnetic resonance imaging and different metrics of ST-segment recovery. Electrocardiograms were assessed at baseline and 90 minutes after primary percutaneous coronary intervention. Three methods for calculating and categorizing ST-segment recovery were used: (1) summed ST-segment deviation (STD) resolution analyzed in 3 categories (> or = 70%, > or = 30% to <70%, and <30%); (2) single-lead STD resolution analyzed in the same 3 categories; (3) worst-lead residual STD analyzed in 3 categories (<1 mm, 1 to <2 mm, and > or = 2 mm). Infarct size and ejection fraction were assessed at 4 months by cardiac magnetic resonance imaging. All 3 ST-segment recovery algorithms predicted the final infarct size and cardiac function. Worst-lead residual STD performed the same as, or better than, the more complex methods and identified large subgroups at either end of the risk spectrum (median infarct size from the lowest to highest risk category (percentage of left ventricle: 7.7% [interquartile range 10.8], 13.1% [interquartile range 13.6]; 24.6% [interquartile range 21.1]); with adjusted odds ratios for infarct size greater than the median (reference <1 mm): 1 to <2 mm, odds ratio 2.3 (95% confidence interval 0.8 to 5.9); > or = 2 mm, odds ratio 6.3 (95% confidence interval 1.7 to 23.7; c-index 0.781). In conclusion, an electrocardiogram obtained early after primary percutaneous coronary intervention analyzed by a simple algorithm provided prognostic information on the final infarct size and cardiac function., (Copyright 2010 Elsevier Inc. All rights reserved.)