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1.  Predictors of mitral annulus early diastolic velocity: impact of long-axis function, ventricular filling pattern, and relaxation 
Although left ventricular (LV) relaxation is well recognized as a predictor of mitral annulus (MA) early diastolic (E′) velocity, its significance relative to other predictors of E′ is less well understood.
Methods and results
We assessed 40 healthy volunteers, 43 patients with acutely decompensated chronic systolic heart failure (HF), and 36 patients with hypertrophic obstructive cardiomyopathy (HOCM) using echocardiography and right or left heart catheterization. Data were obtained at baseline. In addition, in healthy volunteers haemodynamics were varied by graded saline infusion and low body negative pressure, while in HF patients it was varied by vasoactive drug treatment. E- and A-wave velocity (E/A) ratio of the mitral valve inflow, systolic MA velocity integral (s′ integral) and E′ and late velocity (A′) of lateral and septal MA pulsed wave velocities were assessed by echocardiography. Time constant of isovolumic pressure decay τ0) was calculated from isovolumic relaxation time/[ln(aortic dicrotic notch pressure) – ln(LV filling pressure)]. In all three groups, s′ integral was the strongest predictor of E′ (partial r= 0.53–0.79; 0.81 for three groups combined), followed by E/A ratio (partial r= 0.10–0.78; 0.26 for all groups combined) and τ0 (partial r= −0.1 to 0.023; −0.21 for all groups combined).
In healthy adults, patients with systolic HF, or patients with HOCM, E′ is related to LV long-axis function and E/A ratio, a global marker of LV filling. E′ appears less sensitive to LV relaxation.
PMCID: PMC3216376  PMID: 21865226
Echocardiography; Relaxation; Tissue Doppler; Heart failure
2.  Prevalence of infective endocarditis in patients with Staphylococcus aureus bacteraemia: the value of screening with echocardiography 
Staphylococcus aureus infective endocarditis (IE) is a critical medical condition associated with a high morbidity and mortality. In the present study, we prospectively evaluated the importance of screening with echocardiography in an unselected S. aureus bacteraemia (SAB) population.
Methods and results
From 1 January 2009 to 31 August 2010, a total of 244 patients with SAB at six Danish hospitals underwent screening echocardiography. The inclusion rate was 73% of all eligible patients (n= 336), and 53 of the 244 included patients (22%; 95% CI: 17–27%) were diagnosed with definite IE. In patients with native heart valves the prevalence was 19% (95% CI: 14–25%) compared with 38% (95% CI: 20–55%) in patients with prosthetic heart valves and/or cardiac rhythm management devices (P= 0.02). No difference was found between Main Regional Hospitals and Tertiary Cardiac Hospitals, 20 vs. 23%, respectively (NS). The prevalence of IE in high-risk patients with one or more predisposing condition or clinical evidence of IE were significantly higher compared with low-risk patients with no additional risk factors (38 vs. 5%; P < 0.001). IE was associated with a higher 6 months mortality, 14(26%) vs. 28(15%) in SAB patients without IE, respectively (P < 0.05).
SAB patients carry a high risk for development of IE, which is associated with a worse prognosis compared with uncomplicated SAB. The presenting symptoms and clinical findings associated with IE are often non-specific and echocardiography should always be considered as part of the initial evaluation of SAB patients.
PMCID: PMC3117467  PMID: 21685200
Infective endocarditis; Echocardiography; Staphylococcus aureus; Screening
3.  Heritability of left ventricular structure and function in Caucasian families 
The aim of this study was to investigate the heritability as well as genetic and environmental correlations of left ventricular (LV) structural and functional traits in complex pedigrees of a Caucasian population.
Methods and results
We randomly recruited 459 white European subjects from 52 families (50% women; mean age 45 years). LV structure was measured by M-mode and 2D echocardiography and LV function was measured by conventional Doppler and tissue Doppler imaging (TDI). Other measurements included blood pressure, anthropometric, and biochemical measurements. We estimated the heritability of LV traits while adjusting for covariables, including sex, age, body height and weight, systolic and diastolic blood pressures, and heart rate. With full adjustment, heritability of LV mass was 0.23 (P= 0.025). The TDI-derived mitral annular velocities Ea and Aa showed moderate heritability (h2= 0.36 and 0.53, respectively), whereas the mitral inflow A peak had weak heritability (h2 = 0.25) and the E peak was not heritable (h2 = 0.11). We partitioned the total phenotypic correlation when it reached significance, into a genetic and an environmental component. The genetic correlations were 0.61 between the E and Ea peaks and 0.90 between the A and Aa peaks.
Our study demonstrated moderate heritability for LV mass as well as the mitral annular Ea and Aa peaks. We also found significant genetic correlations between the E and Ea peaks and between the A and Aa peaks. Our current findings support the ongoing research to map and detect genetic variants that contribute to the variation in LV mass and other LV structural and functional phenotypes.
PMCID: PMC3106286  PMID: 21398654
Echocardiography; Heritability; Left ventricular phenotypes; Population science
4.  Effect of modest alcohol consumption over 1–2 weeks on the coronary microcirculation of normal subjects 
It has been reported that imbibing red wine increases coronary blood flow reserve acutely. In the absence of changes in coronary driving pressure, any increases in coronary blood flow reserve should occur through a decrease in capillary resistance, which in turn is determined by capillary dimensions and whole-blood viscosity. Since alcohol intake is unlikely to acutely change capillary dimensions, we hypothesized that it must increase coronary blood flow reserve by reducing whole-blood viscosity.
Methods and results
Forty-five normal subjects were randomly assigned to water (n = 12), vodka (n = 11), white wine (n = 11), and red wine (n = 11). Myocardial blood flow reserve was measured at baseline and after up to 2 weeks of beverage consumption using myocardial contrast echocardiography. In addition, whole-blood viscosity and its principal determinants (haematocrit; erythrocyte deformability, mobility, and charge; plasma fibrinogen; and total serum protein, glucose, and lipids) were also measured. Systolic and diastolic blood pressure and heart rate did not change between the two examinations either at rest or following dipyridamole infusion. Neither did myocardial blood flow reserve nor whole-blood viscosity or any of its determinants. Only high-density lipoprotein-2 increased for all alcohol consumers (12.4 ± 5.3 vs. 10.9 ± 4.7, P = 0.007).
It is concluded that modest alcohol consumption for up to 2 weeks does not increase myocardial blood flow reserve. It also does not alter whole-blood viscosity or any of its principal determinants. Therefore, the beneficial cardiovascular effects of modest alcohol consumption over 1–2 weeks cannot be attributed either to its effect on the coronary microcirculation or haemorheology.
PMCID: PMC2935250  PMID: 20378684
Alcohol; Myocardial blood flow reserve; Microcirculation
5.  Diagnostic influence of cardiovascular screening by pocket-size ultrasound in a cardiac unit 
We aimed to study the diagnostic influence of adding a routine cardiovascular ultrasound screening of the cardiac anatomy and function, the pericardium, the pleura and the abdominal great vessels by the new pocket-size ultrasound device (pUS) with grey scale and colour Doppler imaging.
Methods and results
In 119 randomly selected patients admitted to a cardiac unit at a non-university hospital, routinely adding a cardiovascular ultrasonography of only 4.4 min with a pocket-size device corrected the primary diagnosis in 16% of patients. In addition, 29% had the primary diagnosis verified and in 10% an additional important diagnosis was made. Higher age predicted any diagnostic influence of pUS screening with an increase of 61% (P = 0.003) per 10 years of higher age. Overall, the pUS screening had a sensitivity and specificity with respect to detecting at least moderate pathology of 97 and 93%. Positive and negative predictive values were 93 and 87%, respectively. In the sub-group of subjects with a change in the primary diagnosis following pUS there was no false-negative or false-positive findings.
Screening by pUS assessed vascular and cardiac anatomy and function accurately and enabled correction of the diagnosis in 16% of patients admitted to a cardiac unit. In 55% of the participants, the cardiovascular ultrasound screening had important diagnostic influence. We suggest that it would be appropriate to implement strategies and systems for routinely adding an ultrasound cardiovascular examination to patients in cardiac units.
PMCID: PMC3192508  PMID: 21821611
Echocardiography; Vscan; Hand-held; Scanner; Workflow; Device
6.  Feasibility and reliability of point-of-care pocket-sized echocardiography 
To study the reliability and feasibility of point-of-care pocket-sized echocardiography (POCKET) at the bedside in patients admitted to a medical department at a non-university hospital.
Methods and results
One hundred and eight patients were randomized to bedside POCKET examination shortly after admission and later high-end echocardiography (HIGH) in the echo-lab. The POCKET examinations were done by cardiologists on their ward rounds. Assessments of global and regional left ventricular (LV) function, right ventricular (RV) function, valvular function, left atrial (LA) size, the pericardium and pleura were done with respect to effusion and measurements of inferior vena cava (IVC) and abdominal aorta (AA) were performed. Correlations between POCKET and HIGH/appropriate radiological technique for LV function, AA size and presence of pericardial effusion were almost perfect, with r ≥ 0.92. Strong correlation (r ≥ 0.81) was shown for RV and valvular function, except for grading of aortic stenosis (r = 0.62). The correlations were substantial for IVC and LA dimensions. Median time used for bedside screening with POCKET was 4.2 min (range: 2.3–13.0). There was excellent feasibility for cardiac structures and pleura, which was assessed to satisfaction in ≥94% of patients. Lower feasibility (71–79%) was seen for the abdominal great vessels.
Point-of-care semi-quantitative evaluation of cardiac anatomy and function showed high feasibility and correlation with the reference method for most indices. Pocket-sized echocardiographic examinations of ∼4 min length, performed at the bedside by experts, offers reliable assessment of cardiac structures, the pleural space and the large abdominal vessels.
Clinical trial registration:; unique ID: NCT01081210.
PMCID: PMC3171198  PMID: 21810825
Echocardiography; Pocket-size; Hand-held; Screening; Point-of-care ultrasound; Bedside
7.  Three-dimensional simultaneous strain–volume analysis describes left ventricular remodelling and its progression: a pilot study 
Three-dimensional (3D)-echocardiography speckle imaging allows the evaluation of frame-by-frame strain and volume changes simultaneously. The aim of the present investigation was to describe the strain–volume combined assessment in different patterns of cardiac remodelling.
Methods and results
Fifty patients received a 3D acquisition. Patients were classified as follows: healthy subjects (CNT), previous AMI, and normal ejection fraction (EF; group A); ischaemic cardiomyopathy with reduced EF (group B); hypertrophic/infiltrative cardiomyopathy (group C). Values of 3D strain were plotted vs. volume for each frame to build a strain–volume curve for each case. Peak of radial, longitudinal, and circumferential systolic strain (Rɛp, Lɛp, and Cɛp, respectively), slopes of the curves (RɛSl, LɛSl, CɛSl), and strain to end-diastolic volume (EDV) ratio (Rɛ/V, Lɛ/V, Cɛ/V) were computed for the analysis. Strain–volume curves of the CNT group were steep and clustered, whereas, due to progressive dilatation and reduction of strains, progressive flattening could be demonstrated in groups A and B. Quantitative data supported visual assessment with progressive lower slopes (P< 0.05 for RɛSl, CɛSl, P= 0.06 for LɛSl) and significantly lower ratios (P< 0.01 for Rɛ/V, Lɛ/V, and Cɛ/V). Group C showed an opposite behaviour with slopes and ratios close to those of normal subjects. Correlation coefficients between EDV and slopes of the curves were significant for all the directions of strain (CɛSl: r = 0.891; RєSl: r = 0.704; LєSl: r = 0.833; P< 0.0001 for all).
We measured left ventricular volumes and strain by 3D-echo and obtained strain–volume curve to evaluate their behaviour in remodelling. A distinctive and progressive pattern consistent with pathophysiology was observed. The analysis here shown could represent a new non-invasive method to assess myocardial mechanics and its relationship with volumes.
PMCID: PMC3135213  PMID: 21676962
Remodelling; Speckle strain; 3D-echocardiography
8.  Prediction of the annuloplasty ring size in patients undergoing mitral valve repair using real-time three-dimensional transoesophageal echocardiography 
We sought to investigate the additional value of real-time three-dimensional transoesophageal echocardiography (RT 3D TOE)-guided sizing for predicting annuloplasty ring size during mitral valve repair.
Methods and results
In 53 patients undergoing elective mitral valve repair, an RT 3D TOE was performed pre- and post-operatively. The digitally stored loops were imported into a software for mitral valve assessment. The annuloplasty ring size was predicted by superimposing computer-aided design (CAD) models of annuloplasty rings onto Live 3D zoom loops, measurement of the intercommissural distance, or the height of the anterior mitral leaflet. The surgeon implanted the annuloplasty ring according to the usual surgical technique and was blinded to the echocardiographic measurement results. Pre-operative correlation between the selected ring size with mitral valve assessment and the actual implanted annuloplasty ring size was 0.91. The correlation for measurement of the intercommissural distance was 0.55 and for measurement of the height of the anterior mitral leaflet 0.75. The post-operative correlation with the actual implanted ring size was 0.96 for mitral valve assessment, 0.92 for intercommissural distance, and 0.79 for the anterior mitral leaflet height.
Superimposition of annuloplasty ring CAD models on the Live 3D zoom loops of the mitral valve using mitral valve assessment is superior to two-dimensional measurements of the intercommissural distance or the height of the anterior mitral leaflet in predicting correct annuloplasty ring size.
PMCID: PMC3117468  PMID: 21546375
Real-time three-dimensional echocardiography; Transoesophageal echocardiography; Mitral valve repair; Intercommissural distance; Anterior mitral leaflet; Annuloplasty ring
9.  Non-invasive assessment of left ventricular relaxation during atrial fibrillation using mitral flow propagation velocity† 
To elucidate the usefulness of the early diastolic mitral flow propagation velocity (Vp) obtained from colour M-mode Doppler for non-invasively assessing left-ventricular (LV) relaxation during atrial fibrillation (AF).
Methods and results
Ten healthy adult dogs were studied to correlate Vp with the invasive minimum value of the first derivative of LV pressure decay (dP/dtmin) and the time constant of isovolumic LV pressure decay (τ) at baseline, during rapid and slow AF, and during AF after inducing myocardial infarction. There were significant positive and negative curvilinear relationships between Vp and dP/dtmin and τ, respectively, during rapid AF. After slowing the ventricular rate, the average value of Vp increased, while dP/dtmin increased and τ decreased. After inducing myocardial infarction, the average value of Vp decreased, while dP/dtmin decreased and τ increased.
The non-invasively obtained Vp evaluates LV relaxation even during AF regardless of ventricular rhythm or the presence of pathological changes.
PMCID: PMC2760444  PMID: 19692424
Mitral flow propagation velocity; Atrial fibrillation; The first derivative of left ventricular pressure decay; The time constant of isovolumic left ventricular pressure decay
10.  Association between troponin T and impaired left ventricular relaxation in patients with acute decompensated heart failure with preserved systolic function 
To examine relationships between cardiac troponin T (cTnT) and parameters of left ventricular (LV) structure and function in patients with acute destabilized heart failure (HF) with preserved LV ejection fraction.
Methods and results
In 44 patients with acute heart failure (HF) with preserved left ventricular (LV) ejection fraction, parameters of LV structure and function were assessed via comprehensive two-dimensional Doppler echocardiography. There was no correlation between cTnT and LV wall thickness, left atrial volume index, or transmitral E wave velocity or deceleration time. There were associations between cTnT and LV end-diastolic dimension (r = −0.34, P = 0.02) and LV mass index (r = 0.32; P = .04). A lower tissue Doppler Ea wave peak velocity was associated with higher cTnT concentrations (r = −0.90, P < 0.001). In multivariate analyses, only LV end-diastolic dimension (t = 2.2; P = 0.04), LV mass index (t = 2.3; P = .03), and tissue Doppler Ea wave peak velocity (t = −4.7; P < .001) emerged as significant predictors of cTnT.
In patients with HF with preserved LV ejection fraction, cTnT is strongly associated with the extent of LV relaxation abnormalities and LV mass.
PMCID: PMC2733766  PMID: 19483204
Heart failure; Diastolic dysfunction; Biomarker; Echocardiography
11.  Assessment of right ventricular function by real-time three-dimensional echocardiography improves accuracy and decreases interobserver variability compared with conventional two-dimensional views 
Two-dimensional echocardiographic (2DE) assessment of right ventricular (RV) function is difficult, often resulting in inconsistent RV evaluation. Real-time three-dimensional echocardiography (RT3DE) allows the RV to be viewed in multiple planes, which can potentially improve RV assessment and limit interobserver variability when compared with 2DE.
Methods and results
Twenty-five patients underwent 2DE and RT3DE. Views of 2DE (RV inflow, RV short axis, and apical four-chamber) were compared with RT3DE views by four readers. RT3DE data sets were sliced from anterior–posterior (apical view) and from base to apex (short axis) to obtain six standardized planes. Readers recorded the RV ejection fraction (RVEF) from 2DE and RT3DE images. RVEF recorded by RT3DE (RVEF3D) and 2D (RVEF2D) were compared with RVEF by disc summation (RVEFDS), which was used as a reference. Interobserver variability among readers of RVEF3D and RVEF2D was then compared. Overall, mean RVEFDS, RVEF3D, and RVEF2D were 37 ± 11%, 38 ± 10%, 41 ± 10%, respectively. The mean difference of RVEF3D − RVEFDS was significantly less than RVEF2D–RVEFDS (3.7 ± 4% vs. 7.1 ± 5%, P = 0.0066, F-test). RVEF3D correlated better with RVEFDS (r = 0.875 vs. r = 0.69, P = 0.028, t-test). RVEF3D was associated with a 39% decrease in interobserver variability when compared with RVEF2D [standard deviation of mean difference: 3.7 vs. 5.1, (RT3DE vs. 2DE), P = 0.018, t-test].
RT3DE provides improved accuracy of RV function assessment and decreases interobserver variability when compared with 2D views.
PMCID: PMC3003552  PMID: 19258335
Right ventricle function; Three-dimensional echocardiography
12.  Derivation of a size-independent variable for scaling of cardiac dimensions in a normal paediatric population 
It is general practice to correct cardiac chamber size for body size by the process of scaling or normalization. Normalization is most commonly performed using simple linear or isometric correction; however, there is increasing evidence that this approach may be flawed. Likewise, there is little agreement concerning the appropriate scaling variable (measure of body size) for normalization. Therefore, we aimed to establish the optimal method for correcting the differences in body size in a large population of echocardiographically normal paediatric subjects.
Methods and results
We compared the relative ability of standard size variables including height (HT), body weight (BW), body mass index (BMI), and body surface area (BSA), in both isometric and allometric models, to remove the effect of body size in 4109 consecutive echocardiographically normal subjects <18 years of age, using the left atrial dimension (LAD) as a reference standard. Simple linear normalization resulted in significant residual correlations (r = −0.57 to −0.92) of the indexed value with the body size variable, the correlations with weight (WT) and BSA actually increasing. In contrast, correction by the optimal allometric exponent (AE) removed the effects of the indexed variable (residual correlations −0.01 to 0.01), with BW and BSA best removing the effects of all the measures of body size.
Conventional linear correction for body size is inaccurate in children and paradoxically increases the relationship of the indexed parameter with WT and BSA. Conversely, correction using the optimal AE removes the effect of that variable, with WT best correction for all measures of body size.
PMCID: PMC2724882  PMID: 18490317
Scaling; Allometric; Echocardiography; Linear; Classification
13.  The associations between tricuspid annular plane systolic excursion (TAPSE), ventricular dyssynchrony, and ventricular interaction in heart failure patients 
Ventricular interactions may be mediated by loading conditions and biventricular timing and coordination. We sought to understand the relationships between right (RV) and left ventricular (LV) function and dyssynchrony, examine the RV correlates of LV dyssynchrony, and determine whether improved loading conditions affect inter-ventricular interaction.
Methods and results
In 25 heart failure patients [15 with left ventricular ejection fraction (LVEF) < 40%; 10 with LVEF ≥ 50%], Doppler echocardiography and invasive bi-ventricular pressure–volume haemodynamics were obtained at baseline and 30 min after infusion of the recombinant B-type natriuretic peptide vasodilator nesiritide. RV and LV intra-ventricular dyssynchrony was measured invasively using a pressure–conductance catheter. Patients with reduced LVEF had greater LV dyssynchrony (31 ± 3 vs. 24 ± 7%; P = 0.003) compared to those with preserved LVEF. Tricuspid annular plane systolic excursion (TAPSE) had the highest correlation with LV dyssynchrony (r = −0.52; P = 0.0002) compared to other RV echocardiographic parameters. The association between TAPSE and LV dyssynchrony was independent of RVEF and LVEF (P = 0.008). There were no acute changes in the correlations between LV dyssynchrony and TAPSE after nesiritide.
TAPSE and LV dyssynchrony are strongly associated, independent of RV and LV ejection fraction. Of the RV echocardiographic parameters, TAPSE has the highest predictive value of LV dyssynchrony, and remained significant after vasodilator unloading.
PMCID: PMC2724884  PMID: 18490286
Heart failure; Dyssynchrony; Brain natriuretic peptide; hemodynamics
14.  Major weight loss prevents long-term left atrial enlargement in patients with morbid and extreme obesity 
To assess long-term changes in left atrial (LA) volume in patients with morbid obesity [body mass index (BMI) ≥35 kg/m2 with co-morbidities] and extreme obesity (BMI ≥40 kg/m2), after surgically-induced weight loss (WL) after gastric bypass surgery.
Methods and results
We reviewed 57 patients who underwent gastric bypass surgery and had echocardiograms both before and after the operation. A control group was frequency-matched for BMI, sex, age, and for duration of follow-up. After a mean follow-up of 3.6 years, LA volume did not change significantly in patients who underwent bariatric surgery, but increased in the control group by 15 ± 28 ml (P < 0.0001), and 0.1 ± 0.2 ml (P < 0.0001) for height-indexed LA volume, with a difference between cases and controls that remained significant after adjusting for potential confounders (P = 0.01). In the study population as a whole, there was a positive correlation between change in body weight and change in LA volume (r = 0.22, P = 0.006) independent of clinical conditions associated with LA enlargement.
Change in body weight is associated with change in LA size independent of obesity-associated co-morbidities. Successful WL induced by bariatric surgery prevents the progressive increase in LA volume.
PMCID: PMC2724883  PMID: 18490311
Obesity; Bariatric surgery; Left atrial volume; Diastolic function

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