Contrast echocardiography: mechanism of action, safety and clinical applications.

Since its initial description by Gramiak and Shah in 1968, contrast echocardiography has become an established practice world-wide. Microbubbles have the unique property of being pure intravascular tracers. The basic rationale behind bubble imaging is the characteristic responses to ultrasound power that results in enhanced ultrasound images from the blood pool. Therefore, whenever there is blood pool there is a potential application for contrast ultrasound. Clinical applications of contrast echocardiography have been vastly grown from diagnostic applications such as detection of a persistent foramen ovale to drug delivery. This article reviews the mechanism of action, safety and clinical applications of contrast echocardiography.

Cardiac involvement in adults with Pompe disease.

BACKGROUND: Glycogen storage disease type II or Pompe disease is a neuromuscular disorder caused by deficiency of lysosomal acid alpha- glucosidase. Classic infantile Pompe disease results in massive left ventricular (LV) hypertrophy and failure. Although Pompe disease is often included in the differential diagnosis of LV hypertrophy the true frequency of cardiac involvement in adults with Pompe disease is not known. METHODS: Forty-six consecutive adult patients (mean age 48 +/- 12, 22 men) with Pompe disease were included. Each patient underwent a clinical examination, electrocardiography, and rest and low-dose dobutamine (in 20 patients) two-dimensional echocardiography including contrast and tissue Doppler imaging. RESULTS: All patients had limited exercise tolerance; a rollator walking aid was used in seven patients (15%), a wheelchair in 13 patients (28%), and assisted ventilation in 14 patients (30%). Prior to this study, one patient was known with permanent atrial fibrillation, His-bundle ablation and a VVI pacemaker and another patient was known with fluid retention. The first patient had increased LV end-diastolic diameter, impaired LV ejection fraction, low systolic mitral annular velocities and diastolic dysfunction grade II. The patient with fluid retention was wheelchair bound and dependent on 24-h assisted ventilation and showed right ventricular and LV hypertrophy (septum 16 mm, posterior wall 15 mm). LV hypertrophy was not seen in any of the other patients. One woman of advanced age had isolated low systolic mitral annular velocities. Mean global systolic LV function, including contractile reserve, was not decreased in patients with Pompe disease. Eight patients (17%) had mild diastolic dysfunction grade I, related to hypertension in four and advanced age in seven. CONCLUSIONS: In adult patients with Pompe disease without objective signs of cardiac affection by 12-leads electrocardiography or physical examination, echocardiographic screening for LV hypertrophy seems not effective.

Cardiac evaluation in children and adults with Pompe disease sharing the common c.-32-13T>G genotype rarely reveals abnormalities.

BACKGROUND AND OBJECTIVE: Pompe disease is an inherited metabolic disorder caused by deficiency of acid alpha-glucosidase. All affected neonates have a severe hypertrophic cardiomyopathy, leading to cardiac failure and death within the first year of life. We investigated the presence and extent of cardiac involvement in children and adults with Pompe disease with the common c.-32-13T>G genotype to determine the usefulness of cardiac screening in these patients with relatively 'milder' phenotypes. METHODS: Cardiac dimensions and function were evaluated through echocardiography, electrocardiography and Holter monitoring. The total group comprised 68 patients with Pompe disease, of whom 22 patients had disease onset before the age of 18. RESULTS: Two patients (3%) had cardiac abnormalities possibly related to Pompe disease: Electrocardiography showed a Wolff-Parkinson-White pattern in an 8-year-old girl, and one severely affected adult patient had a mild hypertrophic cardiomyopathy. This hypertrophy did not change during treatment with recombinant human alpha-glucosidase. In addition, four adult patients showed minor cardiac abnormalities which did not exceed the prevalence in the general population and were attributed to advanced age, hypertension or pre-existing cardiac pathology unrelated to Pompe disease. CONCLUSIONS: Cardiac involvement is rare in Pompe patients with the common c.-32-13T>G genotype. The younger patients were not more frequently affected than the adults. Electrocardiographic evaluation appears to be appropriate as initial screening tool. Extensive cardiac screening seems indicated only if the electrocardiogram is abnormal or the patient has a history of cardiac disease.

Is there alteration in aortic stiffness in Leber hereditary optic neuropathy?

PURPOSE: Leber hereditary optic neuropathy (LHON) is recognized as the most common cause of isolated blindness in young men. The current study was designed to test whether LHON as a mitochondrial disease is associated with vascular functional alterations characterized by aortic elastic properties during echocardiography. METHODS: A total of 19 patients with typical features of LHON aged 42+/-13 years (10 males) were included. Their results were compared to 19 age- and gender-matched healthy controls. Aortic stiffness index was calculated from the echocardiographically derived aortic diameters and the clinical blood pressure data. RESULTS: In this patient population, the point mutation was present in 3460G>A position in five cases, in 11778G>A position in five cases, and in 14484T>C position in nine patients. Diastolic aortic diameter (26.0+/-2.5 mm vs 28.4+/-4.1 mm, p<0.05) and aortic stiffness index (5.1+/-2.6 vs 12.0+/-7.9, p<0.05) were significantly increased in LHON patients compared to controls. CONCLUSIONS: Aortic stiffness can be increased in LHON disease, but further studies are warranted to confirm these findings in a larger LHON patient population with a more reliable method focusing on the pathophysiologic background.

Dobutamine stress MRI versus threedimensional contrast echocardiography: It's all Black and White.

Dobutamine stress magnetic resonance imaging is considered the superior stress modality to detect wall motion abnormalities. In this report we demonstrate the strengths of a newly developed stress modality: dobutamine stress contrastenhanced real-time three-dimensional echocardiography. This stress modality may become a competitor of stress magnetic resonance imaging allowing fast acquisition and an unlimited number of left ventricular cross sections. Unfortunately, at the moment adequate imaging with stress realtime three-dimensional echocardiography is only possible in a minority of cardiac patients. (Neth Heart J 2008;16:217-8.).

Assessment of left ventricular ejection fraction with late-systolic and mid-diastolic cardiac phases using multi-slice computed tomography.

INTRODUCTION: Multi-slice computed tomography (MSCT) is an accurate tool for the assessment of left ventricular ejection fraction (LVEF). However, in order to reduce radiation dose, prospective acquisition protocols are currently used, in which the end-systole and end-diastole are not scanned. Our aim was to study the accuracy of the assessment of LVEF using fixed late-systolic and mid-diastolic cardiac phases compared with echocardiography. METHODS: MSCT-derived LVEF was measured with off-line commercially available software packages, and compared with echocardiography-derived LVEF using the Simpson's method. LVEF was categorized as normal vs. abnormal (50% cut-off) and was also analyzed as a quantitative parameter. Bland-Altman plots and Pearson correlations were used for inter-technique comparisons. RESULTS: 58 patients were included. The sensitivity and specificity of fixed-phase MSCT when compared with echocardiography for detection of LVEF ≤50% was 79% (95% CI = 65-89%) and 43% (10-82%). Misclassification was associated with older age (68 ± 12 vs. 54 ± 13 years, p < 0.01), faster heart rate (79 ± 14 vs. 68 ± 10 bpm, p = 0.01), and LV hypertrophy (86% vs. 52%, p = 0.03). The quantitative comparison revealed no correlation (r = 0.095, p = 0.478) and a significantly different LVEF (median[IQR], 57.0[50.5-63.1]% vs. 61.0[57.3-64.3]%, p = 0.03). The observed bias between the two methods was -3.7% with broad limits of agreement (±25.5%). CONCLUSIONS: Fixed-phase MSCT assessment using late-systole and mid-diastole agreed in defining normal and abnormal LVEF in 76% of patients when compared with echocardiography. Quantitation of LVEF by this method yielded significantly lower values of LVEF and showed no correlation. Thus, accurate quantitation of LVEF by MSCT requires the acquisition of end-systolic and end-diastolic phases.

Cardiac abnormalities in adults with the attenuated form of mucopolysaccharidosis type I.

BACKGROUND: Cardiac involvement in mucopolysaccharidosis type I (MPS I) has been studied primarily in its most severe forms. Cardiac involvement, particularly left ventricular (LV) systolic and diastolic function, in the attenuated form of MPS I is less well known. METHODS: Cardiac function was prospectively investigated in 9 adult patients with the attenuated form of MPS I. All patients underwent 12-lead electrocardiography, 24 h Holter monitoring and two-dimensional echocardiography including tissue Doppler imaging (TDI). Eighteen age- and sex-matched healthy volunteers served as a control group. RESULTS: Aortic, mitral and tricuspid valve thickening was seen in, respectively, 5 (56%), 4 (44%) and 2 (22%) patients. Moderate mitral valve stenosis was seen in 1 patient and moderate aortic stenosis in 2 patients. All patients had mild-to-moderate aortic and mitral valve regurgitation and 6 patients (67%) had mild-to-moderate tricuspid valve regurgitation. Despite normal LV dimensions, ejection fraction and mass index, MPS patients had lower mean systolic mitral annular velocities (6.1 +/- 0.6 vs 9.1 +/- 1.4 cm/s, p < 0.01) compared to normal control subjects. Similarly, mean early diastolic mitral annular velocities were lower in MPS patients (7.8 +/- 0.9 vs 13.3 +/- 3.3 cm/s, p < 0.01). CONCLUSION: MPS I patients with the attenuated phenotype have not only valvular abnormalities but also LV diastolic and systolic abnormalities.

Influence of the pattern of hypertrophy on left ventricular twist in hypertrophic cardiomyopathy.

BACKGROUND/OBJECTIVE: Left ventricular (LV) twist has an important role in LV function. The influence of the pattern of LV hypertrophy on LV twist in hypertrophic cardiomyopathy (HCM) patients is unknown. This study sought to assess LV twist in a large group of HCM patients according to the pattern of LV hypertrophy. METHODS: The final study population consisted of 43 patients with HCM (mean age 43 (15) years, 31 men) and a typical sigmoidal (n = 16) or reverse septal curvature (n = 27) and 43 age-matched and gender-matched healthy control subjects. LV peak systolic rotation (Rot(max)), LV peak systolic twist (Twist(max)) and untwisting at 5%, 10% and 15% of diastole were determined by speckle tracking echocardiography (STE). RESULTS: Compared to control subjects, HCM patients had increased basal Rot(max) (-5.5 degrees (2.3 degrees ) vs -3.4 degrees (1.7 degrees ), p<0.001) and comparable apical Rot(max) (7.3 degrees (3.1 degrees ) vs 7.0 degrees (2.2 degrees ), p = NS), resulting in increased Twist(max) (12.4 degrees (4.0 degrees ) vs 9.9 degrees (2.7 degrees ), p<0.01). Untwisting at 5%, 10% and 15% of diastole was decreased in HCM patients (all p<0.05). There was a striking difference in apical Rot(max )(9.4 degrees (2.8 degrees ) vs 6.0 degrees (2.6 degrees ), p<0.01) and Twist(max) (15.3 degrees (3.2 degrees ) vs 10.6 degrees (3.3 degrees ), p<0.01) between HCM patients with a sigmoidal and reverse septal curvature. CONCLUSIONS: STE may provide novel non-invasive indices to assess LV function in patients with HCM. Apical Rot(max) and Twist(max) in HCM patients are dependent on the pattern of LV hypertrophy.