Reclassification of aortic stenosis by fusion of echocardiography and computed tomography in low-gradient aortic stenosis.

BACKGROUND: The integration of computed tomography (CT)-derived left ventricular outflow tract area into the echocardiography-derived continuity equation results in the reclassification of a significant proportion of patients with severe aortic stenosis (AS) into moderate AS based on aortic valve area indexed to body surface area determined by fusion imaging (fusion AVAi). The aim of this study was to evaluate AS severity by a fusion imaging technique in patients with low-gradient AS and to compare the clinical impact of reclassified moderate AS versus severe AS. METHODS: We included 359 consecutive patients who underwent transcatheter aortic valve implantation for low-gradient, severe AS at two academic institutions and created a joint database. The primary endpoint was a composite of all-cause mortality and rehospitalisations for heart failure at 1 year. RESULTS: Overall, 35% of the population (n = 126) were reclassified to moderate AS [median fusion AVAi 0.70 (interquartile range, IQR 0.65-0.80) cm2/m2] and severe AS was retained as the classification in 65% [median fusion AVAi 0.49 (IQR 0.43-0.54) cm2/m2]. Lower body mass index, higher logistic EuroSCORE and larger aortic dimensions characterised patients reclassified to moderate AS. Overall, 57% of patients had a left ventricular ejection fraction (LVEF) <50%. Clinical outcome was similar in patients with reclassified moderate or severe AS. Among patients reclassified to moderate AS, non-cardiac mortality was higher in those with LVEF <50% than in those with LVEF ≥50% (log-rank p = 0.029). CONCLUSIONS: The integration of CT and transthoracic echocardiography to obtain fusion AVAi led to the reclassification of one third of patients with low-gradient AS to moderate AS. Reclassification did not affect clinical outcome, although patients reclassified to moderate AS with a LVEF <50% had worse outcomes owing to excess non-cardiac mortality.

Endovascular renal sympathetic denervation to improve heart failure with reduced ejection fraction: the IMPROVE-HF-I study.

INTRODUCTION: The aim of the present study was to assess the safety and efficacy of renal sympathetic denervation (RDN) in patients with heart failure with reduced ejection fraction (HFrEF). METHODS: We randomly assigned 50 patients with a left ventricular ejection fraction (LVEF) ≤ 35% and NYHA class ≥ II, in a 1:1 ratio, to either RDN and optimal medical therapy (OMT) or OMT alone. The primary safety endpoint was the occurrence of a combined endpoint of cardiovascular death, rehospitalisation for heart failure, and acute kidney injury at 6 months. The primary efficacy endpoint was the change in iodine-123 meta-iodobenzylguanidine (123I­MIBG) heart-to-mediastinum ratio (HMR) at 6 months. RESULTS: Mean age was 60 ± 9 years, 86% was male and mean LVEF was 33 ± 8%. At 6 months, the primary safety endpoint occurred in 8.3% vs 8.0% in the RDN and OMT groups, respectively (p = 0.97). At 6 months, the mean change in late HMR was -0.02 (95% CI: -0.08 to 0.12) in the RDN group, versus -0.02 (95% CI: -0.09 to 0.12) in the OMT group (p = 0.95) whereas the mean change in washout rate was 2.34 (95% CI: -6.35 to 1.67) in the RDN group versus -2.59 (95% CI: -1.61 to 6.79) in the OMT group (p-value 0.09). CONCLUSION: RDN with the Vessix system in patients with HFrEF was safe, but did not result in significant changes in cardiac sympathetic nerve activity at 6 months as measured using 123I­MIBG.

Transcatheter mitral valve repair in proportionate and disproportionate functional mitral regurgitation-insights from a small cohort study.

BACKGROUND: Functional mitral regurgitation (FMR) can be subclassified based on its proportionality relative to left ventricular function and end-diastolic volume. FMR proportionality could help identify responders to transcatheter edge-to-edge mitral valve repair (MitraClip) in terms of residual FMR and/or clinical improvement. METHODS: This single-centre retrospective cohort study evaluated the feasibility of determining FMR proportionality in symptomatic heart failure patients with reduced left ventricular function who were treated with MitraClip for ≥ moderate-to-severe FMR. Baseline proportionate (pFMR) and disproportionate FMR (dFMR) were distinguished. Patient characteristics and MitraClip procedural outcomes were described. RESULTS: From an overall cohort of 81 eligible FMR patients, 23/81 (28%) had to be excluded due to missing transthoracic echocardiogram parameters, 22/81 were excluded based on FMR severity. The remaining cohort, of 36/81 patients (44%), could be classified into dFMR (n = 26) or pFMR (n = 10). Conduction disorders were numerically increased in dFMR. All cases requiring > 2 clips were in the dFMR group and absence of FMR reduction occurred more frequently with dFMR. POINT OF VIEW/CONCLUSION: Important limitations in terms of imaging acquisition affect the translation of the FMR proportionality concept to a real-world data set. We did observe different demographic and FMR response patterns in patients with proportionate and disproportionate FMR that warrant further investigation.

Patients who do not complete cardiac rehabilitation have an increased risk of cardiovascular events during long-term follow-up.

BACKGROUND: Cardiac rehabilitation (CR) has favourable effects on cardiovascular mortality and morbidity. Therefore, it might reasonable to expect that incomplete CR participation will result in suboptimal patient outcomes. METHODS: We studied the 914 post-acute coronary syndrome patients who participated in the OPTImal CArdiac REhabilitation (OPTICARE) trial. They all started a 'standard' CR programme, with physical exercises (group sessions) twice a week for 12 weeks. Incomplete CR was defined as participation in <75% of the scheduled exercise sessions. Patients were followed-up for 2.7 years, and the incidence of cardiac events was recorded. Major adverse cardiac events (MACE) included all-cause mortality, non-fatal myocardial infarction and coronary revascularisation. RESULTS: A total of 142 (16%) patients had incomplete CR. They had a higher incidence of MACE than their counterparts who completed CR (11.3% versus 3.8%, adjusted hazard ratio [aHR] 2.86 and 95% confidence interval [CI] 1.47-5.26). Furthermore, the incidence of any cardiac event, including MACE and coronary revascularisation, was higher (20.4% versus 11.0%, aHR 1.54; 95% CI 0.98-2.44). Patients with incomplete CR were more often persistent smokers than those who completed CR (31.7% versus 11.5%), but clinical characteristics were similar otherwise. CONCLUSION: Post-ACS patients who did not complete a 'standard' 12-week CR programme had a higher incidence of adverse cardiac events during long-term follow-up than those who completed the programme. Since CR is proven beneficial, further research is needed to understand the reasons why patients terminate prematurely.

Cardiac rehabilitation in patients who underwent primary percutaneous coronary intervention for acute myocardial infarction: determinants of programme participation and completion.

BACKGROUND: Hospital length of stay after acute myocardial infarction (AMI) treated with primary percutaneous coronary intervention (pPCI) has reduced, resulting in more limited patient education during admission. Therefore, systematic participation in cardiac rehabilitation (CR) has become more essential. We aimed to identify patient-related factors that are associated with participation in and completion of a CR programme. METHODS: We identified 3,871 consecutive AMI patients who underwent pPCI between 2003 and 2011. These patients were linked to the database of Capri CR, which provides dedicated, multi-disciplinary CR. 'Participation' was defined as registration at Capri CR within 6 months after pPCI. CR was 'complete' if a patient undertook the final exercise test. RESULTS: In total, 1,497 patients (39%) were registered at Capri CR. Factors independently associated with CR participation included age (<50 vs. >70 year: odds ratio (OR) 7.0, 95% confidence interval (CI) 5.1-9.6), gender (men vs. women: OR 1.9, 95% CI 1.3-1.8), index diagnosis (ST-elevation myocardial infarction [STEMI] vs. non-ST-elevation myocardial infarction [NSTEMI]: OR 2.4, 95% CI 2.0-2.7) and socio-economic status (high vs. low: OR 2.0, 95% CI 1.6-2.5). The model based on these factors discriminated well (c-index 0.75). CR programme completion was 80% and was inversely related with diabetes, current smoking and previous MI. The discrimination of the model based on these factors was poor (c-index 0.59). CONCLUSIONS: Only a minority of AMI/pPCI patients participated in a CR programme. Completion rates, however, were better. Increased physician and patient awareness of the benefits of CR are still needed, with focus on the elderly, women and patients with low socio-economic status.

P1138Cardiac shear wave velocity in healthy individuals.

BACKGROUND: The closure of the valves generates shear waves in the heart walls. The propagation velocity of shear waves relates to stiffness. This could potentially be used to estimate the stiffness of the myocardium, with huge potential implications in pathologies characterized by a deterioration of the diastolic properties of the left ventricle. In an earlier phantom study we already validated shear wave tracking with a clinical ultrasound system in cardiac mode. PURPOSE: In this study we aimed to measure the shear waves velocity in normal individuals. METHODS: 12 healthy volunteers, mean age=37±10, 33% females, were investigated using a clinical scanner (Philips iE33), equipped with a S5-1 probe, using a clinical tissue Doppler (TDI) application. ECG and phonocardiogram (PCG) were synchronously recorded. We achieved a TDI frame rate of >500Hz by carefully tuning normal system settings. Data were processed offline in Philips Qlab 8 to extract tissue velocity along a virtual M-mode line in the basal third of the interventricular septum, in parasternal long axis view. This tissue velocity showed a propagating wave pattern after closure of the valves. The slope of the wave front velocity in a space-time panel was measured to obtain the shear wave propagation velocity. The velocity of the shear waves induced by the closure of the mitral valve (1st heart sound) and aortic valve (2nd heart sound) was averaged over 4 heartbeats for every subject. RESULTS: Shear waves were visible after each closure of the heart valves, synchronous to the heart sounds. The figure shows one heart cycle of a subject, with the mean velocity along a virtual M-mode line in the upper panel, synchronous to the ECG signal (green line) and phonocardiogram (yellow line) in the lower panel. The slope of the shear waves is marked with dotted lines and the onset of the heart sounds with white lines. In our healthy volunteer group the mean velocity of the shear wave induced by mitral valve closure was 4.8±0.7m/s, standard error of 0.14 m/s. The mean velocity after aortic valve closure was 3.4±0.5m/s, standard error of 0.09 m/s. We consistently found that for any subject the velocity after mitral valve closure was higher than after aortic valve closure. CONCLUSION: The velocity of the shear waves generated by the closure of the heart valves can be measured in normal individuals using a clinical TDI application. The shear wave induced after mitral valve closure was consistently faster than after aortic valve closure. Abstract P1138 Figure.Abstract P1138 Figure.

OPTImal CArdiac REhabilitation (OPTICARE) following Acute Coronary Syndromes: Rationale and design of a randomised, controlled trial to investigate the benefits of expanded educational and behavioural intervention programs.

The majority of cardiac rehabilitation (CR) referrals consist of patients who have survived an acute coronary syndrome (ACS). Although major changes have been implemented in ACS treatment since the 1980s, which highly influenced mortality and morbidity, CR programs have barely changed and only few data are available on the optimal CR format in these patients. We postulated that standard CR programs followed by relatively brief maintenance programs and booster sessions, including behavioural techniques and focusing on incorporating lifestyle changes into daily life, can improve long-term adherence to lifestyle modifications. These strategies might result in improved (cardiac) mortality and morbidity in a cost-effective fashion. In the OPTImal CArdiac REhabilitation (OPTICARE) trial we will assess the effects of two advanced and extended CR programs that are designed to stimulate permanent adaption of a heart-healthy lifestyle, compared with current standard CR, in ACS patients. We will study the effects in terms of cardiac risk profile, levels of daily physical activity, quality of life and health care consumption.

Hemodynamic adaptation to pregnancy in women with structural heart disease.

BACKGROUND: Many women with structural heart disease reach reproductive age and contemplate motherhood. Pregnancy induces and requires major hemodynamic changes. Pregnant women with structural heart disease may have a reduced cardiac reserve. There are no longitudinal data on cardiovascular adaptation throughout pregnancy in women with structural heart disease. METHODS: Thirty-five women with structural heart disease were included in a prospective observational trial. Maternal hemodynamics were assessed before conception, during pregnancy and 6 months postpartum by transthoracic echocardiography. Uteroplacental perfusion was analyzed by obstetric Dopplers. Longitudinal evolution over time was analyzed as well as the long term influence of pregnancy on cardiac function. RESULTS: Cardiac output (CO), stroke volume (SV), left ventricular mass (LV mass) and E/E' ratio significantly increased and ejection fraction (EF) and fractional shortening (FS) decreased during pregnancy. There was a statistically significant difference in EF, FS and E/E' ratio before and after pregnancy. CONCLUSIONS: The characteristic pattern of hemodynamic adaptation to pregnancy is attenuated in women with structural heart disease. The pregnancy related volume load induces progression of diastolic dysfunction. Our data suggest a persistent reduction in systolic and diastolic cardiac functions after pregnancy in women with structural heart disease.

Clinical course of patients diagnosed with severe aortic stenosis in the Rotterdam area: insights from the AVARIJN study.

OBJECTIVE: To prospectively evaluate the clinical course of patients with severe aortic stenosis (AS) and identify factors associated with treatment selection and patient outcome. METHODS: Patients diagnosed with severe AS in the Rotterdam area were included between June 2006 and May 2009. Patient characteristics, echocardiogram, brain natriuretic peptide (NT-proBNP), and treatment strategy were assessed at baseline, and after 6, 12, and 24 months. Endpoints were aortic valve replacement (AVR) / transcatheter aortic valve implantation (TAVI) and death. RESULTS: The study population comprised 191 patients, 132 were symptomatic and 59 asymptomatic at study entry. Two-year cumulative survival of symptomatic patients was 89.8 % (95 % CI 79.8-95.0 %) after AVR/TAVI and 72.6 % (95 % CI 59.7-82.0 %) with conservative treatment. Two-year cumulative survival of asymptomatic patients was 91.5 % (95 % CI 80.8-96.4 %). Two-year cumulative incidence of AVR/TAVI was 55.9 % (95 % CI 47.5-63.5 %) in symptomatic patients. Sixty-eight percent of asymptomatic patients developed symptoms, median time to symptoms was 13 months; AVR/TAVI cumulative incidence was 38.3 % (95 % CI 23.1-53.3 %). Elderly symptomatic patients with multiple comorbidities were more likely to receive conservative treatment. CONCLUSIONS: In contemporary Dutch practice many symptomatic patients do not receive invasive treatment of severe AS. Two-thirds of asymptomatic patients develop symptoms within 2 years, illustrating the progressive nature of severe AS. Treatment optimisation may be achieved through careful individualised assessment in a multidisciplinary setting.

Automated analysis of three-dimensional stress echocardiography.

Real-time three-dimensional (3D) ultrasound imaging has been proposed as an alternative for two-dimensional stress echocardiography for assessing myocardial dysfunction and underlying coronary artery disease. Analysis of 3D stress echocardiography is no simple task and requires considerable expertise. In this paper, we propose methods for automated analysis, which may provide a more objective and accurate diagnosis. Expert knowledge is incorporated via statistical modelling of patient data. Methods for identifying anatomical views, detecting endocardial borders, and classification of wall motion are described and shown to provide favourable results. We also present software developed especially for analysis of 3D stress echocardiography in clinical practice. Interobserver agreement in wall motion scoring is better using the dedicated software (96%) than commercially available software not dedicated for this purpose (79%). The developed tools may provide useful quantitative and objective parameters to assist the clinical expert in the diagnosis of left ventricular function.

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.

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.

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.

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.).

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.

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.

Clinical usefulness of SonoVue contrast echocardiography: the Thoraxcentre experience.

Although other imaging techniques, such as magnetic resonance imaging and computer tomography, are becoming more and more important in cardiology, two-dimensional echocardiography is still the most used technique in clinical cardiology. Quantification of left ventricular function and dimensions is important because therapeutic strategies, for example implanting an ICD after myocardial infarction, are based on ejection fraction measurements. Because of the sometimes low quality of echocardiographic images we started to use an ultrasound contrast agent and in this article we describe our experiences with SonoVue, a second-generation contrast agent, over a threeyear period in the Thoraxcentre. (Neth Heart J 2007;15:55-60.).

Coronary flow reserve in hypertrophic cardiomyopathy: relation with microvascular dysfunction and pathophysiological characteristics.

BACKGROUND.: The decrease in coronary flow reserve (CFR) in hypertrophic cardiomyopathy (HCM) predisposes to myocardial ischaemia, systolic dysfunction and cardiac death. In this study we investigate to which extent haemodynamic, echocardiographic, and histological parameters contribute to the reduction of CFR. METHODS.: In ten HCM patients (mean age 44+/-14 years) and eight heart transplant (HTX) patients (mean age 51+/-6 years) CFR was calculated in the left anterior descending coronary artery. In all subjects haemodynamic, echocardiographic and histological parameters were assessed. The relationship between these variables and CFR was determined using linear regression analysis. RESULTS.: CFR was reduced in HCM compared with HTX patients (1.6+/-0.7 vs. 2.7+/-0.8, p<0.01). An increase in septal thickness (p<0.005), indexed left ventricular (LV) mass (p<0.005), LV end-diastolic pressure (p<0.001), LV outflow tract gradient (p<0.05) and a decrease in arteriolar lumen size (p<0.05) were all related to a reduction in CFR. CONCLUSION.: In HCM patients haemodynamic (LV end-diastolic pressure, LV outflow tract gradient), echocardiographic (indexed LV mass) and histological (% luminal area of the arterioles) changes are responsible for a decrease in CFR. (Neth Heart J 2007;15:209-15.).

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.