Effects of switching from agalsidase Beta to agalsidase alfa in 10 patients with anderson-fabry disease.

Anderson-Fabry disease (AFD) is a multiorgan X-linked lysosomal storage disease that particularly affects the heart, kidneys, and cerebrovascular system. Current treatment is enzyme replacement therapy (ERT) with agalsidase beta (Fabrazyme(®), Genzyme Corporation, Cambridge, MA, USA) or agalsidase alfa (Replagal(®), Shire Human Genetic Therapies AB, Lund, Sweden). It was recommended that patients switch to agalsidase alfa due to a manufacturing shortage of agalsidase beta beginning in June 2009. This study assessed the effect of switching to agalsidase alfa on clinical outcomes in patients with AFD previously treated with agalsidase beta. Ten patients (seven male, three female) with genetically confirmed AFD and at least 48 months' continuous data collected during treatment with agalsidase beta 1 mg/kg every other week were switched to agalsidase alfa 0.2 mg/kg every other week for at least 20 months, with prospective clinical evaluations every 6 months. Pre-switch data was collected retrospectively from patient charts. Cardiac functional parameters were assessed using magnetic resonance imaging. Results showed that renal function was normal (estimated glomerular filtration rate ≥90 mL/min/1.73 m(2)) in 8 of 10 patients prior to agalsidase alfa and generally remained stable after the switch. Cardiac mass decreased significantly (p < 0.05 vs pre-ERT) after agalsidase beta and remained unchanged after switching to agalsidase alfa. Symptoms of pain and health status scores did not deteriorate during agalsidase alfa therapy. Adverse events were mostly mild and infusion related. In conclusion, switching to agalsidase alfa was relatively well tolerated and associated with stable clinical status and preserved renal and cardiac function.

Role of cardiac MRI in evaluating patients with Anderson-Fabry disease: assessing cardiac effects of long-term enzyme replacement therapy.

PURPOSE: Anderson-Fabry disease is a multisystemic disorder of lipid metabolism secondary to X-chromosome alterations and is frequently associated with cardiac manifestations such as left ventricular (LV) hypertrophy, gradually leading to an alteration in cardiac performance. The purpose of this study was to monitor, using magnetic resonance imaging (MRI), any changes produced by enzyme replacement therapy with agalsidase beta at the cardiac level in patients with Anderson-Fabry disease. MATERIALS AND METHODS: Sixteen (ten men, six women) patients with genetically confirmed Anderson-Fabry disease underwent cardiac MRI before starting enzyme replacement therapy (baseline study) and after 48 months of treatment with agalsidase beta at the dose of 1 mg/kg (follow-up study). RESULTS: After 48 months of treatment, a significant reduction in LV mass and wall thickness was observed: 187±59 g vs. 149±44 g, and 16±3 mm vs. 13±3 mm, respectively. A significant reduction in T2 relaxation time was noted at the level of the interventricular septum (81±3 ms vs. 67±7 ms), at the apical level (80±8 ms vs. 63±6 ms) and at the level of the lateral wall (82±8 ms vs. 63±10 ms) (p<0.05). No significant variation was observed in ejection fraction between the two studies (65±3% vs. 64±2%; p>0.05) (mean bias 1.0); however, an improvement was noted in the New York Heart Association (NYHA) class of the majority of patients (12/16) (p<0.05). CONCLUSIONS: In patients with Anderson-Fabry disease undergoing enzyme replacement therapy with agalsidase beta, MRI documented a significant reduction in myocardial T2 relaxation time, a significant decrease in maximal myocardial thickness and in total LV mass. MRI did not reveal significant improvements in LV global systolic function; however, improvement in NYHA functional class was noted, consistent with improved diastolic function.

Prognostic value of computed tomography coronary angiography in patients with chest pain of suspected cardiac origin.

PURPOSE: The authors sought to determine the prognostic value of computed tomography coronary angiography (CTCA) in patients with acute chest pain (ACP). MATERIALS AND METHODS: A total of 145 consecutive patients (75 men; 64±12 years) with ACP were referred from the Emergency Department for CTCA, which was performed with a standard protocol using a 64-slice scanner. Patients were stratified according to the Morise clinical score (low, intermediate, high) and to the CTCA findings [absence of coronary artery disease (CAD), nonobstructive CAD, obstructive CAD]. Patients were followed up for the occurrence of major events: cardiac death, nonfatal myocardial infarction, unstable angina and revascularisation. RESULTS: One hundred and twenty-seven (87.6%) patients were without a history of CAD, and 18 (12.4%) patients had a history of CAD. Obstructive CAD (>50% luminal narrowing) was detected in 35 (24%) patients; nonobstructive CAD (≤ 50% luminal narrowing) in 62 (43%) and absence of CAD in 48 (33%) patients. During a mean follow-up of 20 ± 3 months, 20 events occurred (four hard events). Sixteen events (three hard events) occurred in patients without a history of CAD, and four events (one hard event) occurred in patients with a history of CAD. In patients with absence of CAD as detected by CTCA, the rate of events was 0%. At multivariate analysis, hypercholesterolaemia and obstructive CAD were significant predictors of events (p<0.05). CONCLUSIONS: An excellent prognosis was observed in patients with ACP and normal CTCA. CTCA shows the potential for optimal stratification of patients with ACP.

Prognostic value of CT coronary angiography: focus on obstructive vs. nonobstructive disease and on the presence of left main disease.

PURPOSE: The authors investigated the prognostic value of computed tomography coronary angiography (CTCA) for major adverse cardiac events (MACE) in patients with suspected or known coronary artery disease (CAD), with particular focus on left main (LM) disease and obstructive vs. nonobstructive disease. MATERIALS AND METHODS: A total of 727 consecutive patients (485 men, age 62 ± 11 years) with suspected (514; 70.1%) or known (213; 29.9%) CAD underwent CTCA. Patients were followed up for the occurrence of MACE (i.e. cardiac death, nonfatal myocardial infarction, unstable angina, percutaneous/surgical revascularisation). RESULTS: A total of 117 MACE [five cardiac deaths, 11 acute myocardial infarctions (AMI), five unstable angina, 86 percutaneous coronary interventions, ten coronary artery bypass grafts] occurred during a mean follow-up of 20 months. Severity and extension of CAD was associated with a progressively worse prognosis. The event rate was 0% among patients with normal coronary arteries at CTCA. The presence of LM disease was not associated with a worse prognosis either in patients with no history of CAD or in those with a history of CAD. At multivariate analysis, presence of obstructive CAD and diabetes were the only independent predictors of MACE. CONCLUSIONS: Evaluation of atherosclerotic burden by CTCA provides an independent prognostic value for prediction of MACE. Patients with normal CTCA findings have an excellent prognosis at follow-up.

Cardiac magnetic resonance imaging illustrating Anderson-Fabry disease progression.

Anderson-Fabry disease is an X-linked lysosomal storage disorder resulting from a deficiency of the enzyme α-galactosidase A (α-Gal A) and subsequent cellular storage of the enzyme's substrate globotriaosylceramide (Gb3) and related glycosphingolipids. We report a case of Anderson-Fabry disease with cardiac involvement evaluated with cardiovascular MRI. Disease progression was observed despite enzyme replacement therapy.

Left ventricular ejection fraction: real-world comparison between cardiac computed tomography and echocardiography in a large population.

PURPOSE: This study compared cardiac computed tomography (CT) and two-dimensional transthoracic echocardiography (ECC) for assessing left ventricular ejection fraction (LVEF) using real-world data from a large patient population. MATERIALS AND METHODS: We studied 450 patients (284 males; mean age 64±12 years; range 12-88) who underwent CT and ECC due to suspected coronary artery disease. For CT, we used multiphase short-axis reconstructions and evaluated them with a dedicated software tool that uses Simpson's rule to compute LV volumes. For ECC, computation was based on the biplane Simpson's method. Results in terms of EF were compared with the paired Student's t test, Pearson's correlation coefficient (r), and Bland-Altman analysis. RESULTS: EF was 52%±15% for CT and 55%±13% for ECC. Statistically significant differences, albeit with good correlation, were observed between the measurements (r=0.71; p<0.05). ECC showed a slight tendency to overestimate EF. When the population was divided into subgroups according to EF, this was underestimated by ECC in the subgroup with EF >50% and overestimated in those with EF 35%-50% and <35%, with consistently significant differences between ECC and CT (p<0.05) and progressively lower levels of agreement. CONCLUSIONS: In the real-world assessment of EF, ECC provides significantly different data from CT, with a bias that increases proportionally to LV systolic dysfunction.

Functional parameters of the left ventricle: comparison of cardiac MRI and cardiac CT in a large population.

PURPOSE: The authors sought to compare magnetic resonance imaging (MRI) and computed tomography (CT) for assessing left ventricular (LV) function parameters in a large patient population. MATERIALS AND METHODS: The study was conducted on 181 patients who underwent cardiac MRI and cardiac CT for various indications. For MRI, we used two-dimensional cine balanced steady-state free precession (b-SSFP) sequences, and for CT we used multiphase short-axis reconstructions. Volume data sets were evaluated with dedicated software. Results were compared with a paired, two-tailed Student's t test, Pearson's correlation (r), and Bland-Altman analysis. RESULTS: A high level of concordance was observed between cardiac MRI and CT. Ejection fraction (EF) was 53+/-14% for MRI vs. 53%+/-15% for CT. There was good correlation for EF (r=0.71; p>0.05) and end-systolic volume (r=0.74; p>0.05). End-diastolic volume (74+/-23 ml at MRI vs. 71+/-19 ml at CT; r=0.58; p<0.05) and myocardial mass (63+/-20 g at MRI and 56+/-18 g at CT; r=0.89; p<0.01) showed statistically significant differences, although the discrepancy had no clinical impact. CONCLUSIONS: MRI and CT show a good level of agreement in assessing LV function parameters, and both can be used interchangeably in clinical practice.

Assessment of left ventricular volumes with cardiac MRI: comparison between two semiautomated quantitative software packages.

PURPOSE: This study compared two quantitative semiautomated software packages for volumetric analysis of the left ventricle (LV) by magnetic resonance (MR) imaging using two-dimensional (2D) cine balanced steady-state free precession (b-SSFP) sequences. MATERIALS AND METHODS: We included 46 consecutive patients who underwent cardiac MR imaging for various indications. Two-dimensional cine b-SSFP sequences were used to assess the LV. Data sets were evaluated with two dedicated software packages: ViewForum, version 4.2, and Argus, version Va60C. Results were compared with Student's t test for paired samples, Pearson's r correlation coefficient and R2 coefficient of determination; ejection fraction differences were assessed with Bland-Altman analysis. The time required for analysis was also recorded. RESULTS: We observed very high levels of concordance and reproducibility. High correlation was observed for ejection fraction (p>0.05; r=0.9; R (2)=0.82). The time required for analysis was 7.6+/-2.78 min vs. 7.52+/-2.4 min (p>0.05; r=0.85; R (2)=0.73). Intraobserver and interobserver variability did not show significant differences. CONCLUSIONS: LV volume evaluation is an integral part of cardiac MR imaging. In our experience, there is no significant difference between the commonly used software packages in either quantitative output or time required for analysis.

Effects of enzyme-replacement therapy in patients with Anderson-Fabry disease: a prospective long-term cardiac magnetic resonance imaging study.

BACKGROUND: Anderson-Fabry disease is a multisystem X linked disorder of lipid metabolism frequently associated with cardiac symptoms, including left ventricular (LV) hypertrophy gradually impairing cardiac function. Evidence showing that enzyme-replacement therapy (ERT) can be effective in reducing LV hypertrophy and improving myocardial function in the long term is limited. OBJECTIVE: This study aimed to assess the long-term effects of ERT with recombinant alpha-galactosidase A (agalsidase beta, Fabrazyme) on LV function and myocardial signal intensity in 11 patients with Anderson-Fabry disease. PATIENTS: Eleven patients (eight males, three females) with varying stages of genetically confirmed Anderson-Fabry disease were examined by means of physical examination and magnetic resonance imaging before ERT with agalsidase beta at 1 mg/kg every other week (study 1) and after a mean treatment duration of 45 months (study 2). RESULTS: At 45 months of treatment, LV mass and LV wall thickness had significantly reduced: 188 (SD 60) g versus 153 (47) g, and 16 (4) mm versus 14 (4) mm, respectively. Furthermore, a significant reduction in myocardial T2 relaxation times was noted in all myocardial regions, that is, interventricular septum 80 (5) ms versus 66 (8) ms, apex 79 (10) ms versus 64 (10) ms, and lateral wall 80 (8) ms versus 65 (16) ms. Changes in LV ejection fraction were not significant. Amelioration of clinical symptoms was observed in all patients. CONCLUSIONS: Long-term therapy with agalsidase beta at 1 mg/kg every 2 weeks was effective in significantly reducing LV hypertrophy, improving overall cardiac performance and ameliorating clinical symptoms in patients with Anderson-Fabry disease.

Prognostic value of 64-slice coronary angiography in diabetes mellitus patients with known or suspected coronary artery disease compared with a nondiabetic population.

PURPOSE: This study aimed to determine the prognostic value of coronary angiography with multislice computed tomography (MSCT) in a population of diabetic subjects with known or suspected ischaemic heart disease compared with a nondiabetic control population. MATERIALS AND METHODS: Forty-nine patients with type 2 diabetes mellitus (DM) [group 1; mean age 67.7+/-8.8 years; 32 men; mean body mass index (BMI) 28+/-3.9] and 49 patients without DM (group 2, with similar demographic and clinical characteristics) were studied with MSCT coronary angiography to exclude the presence of ischaemic coronary artery disease (CAD). Each group comprised 26 patients (53%) with no history of ischaemic coronary disease and 23 patients (47%) with a history of myocardial infarction and/or myocardial revascularisation. Clinical follow-up was performed by analysing correlations between the rate of cumulative cardiac events (cardiac death, nonfatal myocardial infarction, unstable angina, and myocardial revascularisation), the severity of CAD identified on MSCT, and the presence of DM as a cardiovascular risk factor. RESULTS: At mean follow-up of 20 months, univariate analysis of survival showed significant differences between the two groups (group 1 vs. group 2, p=0.046). Moreover, the cumulative cardiac event rate correlated significantly with the presence of significant CAD (>50% stenosis) in both groups (group 1: p=0.003; group 2: p=0.0004). CONCLUSIONS: Event-free survival is significantly lower in the diabetic population compared with the normal control population (p=0.046) and is closely correlated with the presence of significant CAD. MSCT is an effective method for stratifying such risk and, together with high diagnostic accuracy, provides additional prognostic value.

Prevalence and characteristics of coronary artery disease in a population with suspected ischemic heart disease using CT coronary angiography: correlations with cardiovascular risk factors and clinical presentation.

PURPOSE: This study was undertaken to describe the correlation between the distribution of coronary artery disease (CAD) in a symptomatic population with suspected ischaemic heart disease, cardiovascular risk factors (RF) and clinical presentation. MATERIALS AND METHODS: we studied 163 patients (mean age 65.5 years; 101 men and 62 women) referred for multidetector computed tomography coronary angiography (MDCT-CA) to rule out CAD. The patients had no prior history of revascularisation or myocardial infarction. We analysed how the characteristics of CAD (severity and type of plaque) can change with the increase in RF and how they are related to different clinical presentations. RESULTS: patients were divided into three groups according to the number of RF: zero or one, two or three, and four or more. The percentage of coronary arteries with no plaque, nonsignificant disease and significant disease was 55%, 41% and 4%, respectively, in patients with zero or one RF; 27%, 51% and 22%, respectively, in patients with two or three RF; and 19%, 38% and 44%, respectively, in patients with four or more RF. Plaque in patients with nonsignificant disease was mixed in 65%, soft in 18% and calcified in 17%. The percentage of coronaries with no plaque in the three RF groups was 50%, 20% and 0% in patients with typical chest pain and 46%, 24% and 12% in those with atypical pain. The percentage of significant disease in patients with typical pain was 0%, 47% and 86% and in those with atypical pain 4%, 20% and 29%. CONCLUSIONS: MDCT plays an important role in the identification of CAD in patients with suspected ischaemic heart disease. Severity and type of disease is highly correlated with RF number and assumes different characteristics according to clinical presentation.

Multislice computed tomography coronary angiography: clinical applications.

Cardiac and coronary computed tomography (CT) is becoming increasingly common in clinical practice. Even if there is no well-established evidence, this diagnostic modality is so strong and effective and, in skilled hand, it can be readily used in clinical practice. After learning its potential and the technical limits, this tool could be used for risk stratification as well as for revascularization evaluation. In this review, we will describe the results of present literature, clinical applications at present considered suitable to CT technology (i.e. 64-slice and dual-source scanners) and future applications and innovations.