Heart valve involvement in Fabry cardiomyopathy.

Fabry disease is a rare X-linked lysosomal storage disorder leading to an accumulation of glycosphingolipids in all tissues and organs including the heart. Among the pathologies of myocardial involvement, reviews and registry data list affection of heart valves and its hemodynamic significance as predominant alterations during progression of the disease. We thought to approach this uncertainty with a systematic observational study. In a single center study, 111 patients with genetically proven Fabry disease were systematically investigated by echocardiography for abnormalities of the valves in the left (aortic and mitral valve) and right heart (pulmonary and tricuspid valve). In addition, 60 patients were followed by echocardiography for 2.7 +/- 1.5 y (range 1 to 6). Both valve stenosis and regurgitation were classified as mild, moderate or severe. Overall, no patient had severe heart valve abnormalities. The most frequent findings were mild aortic (n = 17), mitral (n = 57) and tricuspid (n = 38) valve regurgitation. Only two patients showed mild aortic valve stenosis. Moderate aortic (n = 1), mitral (n = 2) or tricuspid (n = 1) regurgitation were rarely detected. All Fabry patients in advanced stages (n = 9) had only mild mitral regurgitation and one of them had mild aortic and mitral regurgitation, moderate tricuspid regurgitation and mild aortic stenosis. Thirty patients had completely normal valve function. There was no significant change toward hemodynamic relevant heart valve abnormalities during follow-up. Mild left ventricular valve regurgitations are frequent in Fabry disease. However, these valve abnormalities are not the major limitations for the Fabry heart.

Progression of left ventricular functional abnormalities in hypertensive patients with heart failure: an ultrasonic two-dimensional speckle tracking study.

OBJECTIVE: Two-dimensional (2-D) strain imaging is a novel echocardiographic technique for myocardial function evaluation. We sought to investigate left ventricular (LV) systolic function in patients with heart failure caused by hypertension using a 2-D strain approach and to validate this method against Doppler strain measurements. METHODS: The study population comprised 81 patients (66.4 +/- 7.4 years) with hypertension in New York Heart Association (NYHA) class I to IV and 20 healthy controls. RESULTS: Decreased longitudinal strain was demonstrated in the basal septal segment in NYHA I, in the basal and mid septal and basal lateral segments in NYHA II, and in all segments in NYHA III and IV. Radial and circumferential strain were reduced in patients with NYHA III and IV. Independent predictors of strain were duration of HT, LV mass index, LV end-diastolic volume index, and systolic blood pressure. The agreement between 2-D and Doppler strain remained within acceptable ranges (mean difference +/- 1 standard deviation: 0.61%-1.92% +/- 2.38%-2.92% for longitudinal strain in particular segments and 4.98% +/- 5.26% for radial strain). CONCLUSION: In hypertensive patients, (1) LV longitudinal systolic function progressively deteriorates from NYHA I to IV and abnormalities commence in the basal septum, (2) LV radial and circumferential systolic impairment appears in NYHA III and IV, and (3) 2-D strain measurement provides a feasible tool for the quantitation of LV systolic performance.

Use of tissue Doppler imaging to identify and manage systemic diseases.

In systemic diseases such as amyloidosis, sarcoidosis, Friedreich's ataxia, Fabry's disease and muscular dystrophy the clinician has to judge the presence and the amount of cardiac involvement. In most of these patients conventional echocardiographic parameters are not sensitive enough to detect sub-clinical dysfunction. Tissue Doppler imaging and in addition strain rate imaging has proven to be very sensitive for the assessment of myocardial dysfunction. This review explores the impact of these new techniques to identify and to manage cardiac aspects of the different systemic diseases.

A new echocardiographic approach for the detection of non-ischaemic fibrosis in hypertrophic myocardium.

AIMS: Regional myocardial fibrosis detected by magnetic resonance imaging (MRI) using late enhancement (LE) indicates an unfavorable prognosis. We investigated in a prospective study whether regional non-ischaemic fibrosis in hypertrophic myocardium can also be detected by ultrasonic strain-rate imaging based on specific visual features of the myocardial deformation traces. METHODS AND RESULTS: This diagnostic study aimed to define left ventricular fibrotic segments in 30 patients with hypertrophic cardiomyopathy (n = 10), severe aortic valve stenosis (n = 10), Fabry disease cardiomyopathy (n = 10), and 10 healthy controls. MRI and strain-rate imaging (=deformation imaging) was performed in all patients and controls to detect LE. In total, 42 segments showed LE according to MRI criteria. Using strain-rate imaging, all LE positive segments displayed a characteristic pattern consisting of a first peak in early systole followed by a rapid fall in strain rate close to zero and a second peak during isovolumetric relaxation. This 'double peak sign' was never seen in segments of healthy controls. However, it was detected in 10 segments without LE. These 'false-positive' segments belonged to Fabry patients who often develop a fast progressing fibrosis. In a follow-up MRI study after 2 years (available for 6/10 segments), all these segments had developed LE. CONCLUSION: The 'double peak sign' in strain-rate imaging tracings seems to be a reliable tool to diagnose regional fibrosis.

Assessment of the contractile reserve in patients with intermediate coronary lesions: a strain rate imaging study validated by invasive myocardial fractional flow reserve.

AIMS: The present study aims to compare the change of left ventricular deformation during dobutamine stress echocardiography (DSE) with the reference standard of invasive myocardial fractional flow reserve (FFR) to assess the haemodynamic significance of intermediate coronary lesions. METHODS AND RESULTS: In 30 patients with an intermediate coronary artery stenosis in one epicardial coronary artery, FFR measurements were performed during coronary catheterization. In case of an FFR < 0.75 after intracoronary adenosine administration, the stenosis was considered significant, indicating ischaemia. In addition, during DSE, peak systolic strain rate and systolic strain of the region of interest (supplied by the stenotic vessel) and of a non-ischaemic remote region were assessed at baseline and at peak stress. Thirteen patients had an FFR >or= 0.75, indicating normal flow reserve (non-ischaemic group). The remaining 17 patients with an FFR < 0.75 comprised the ischaemic group. At baseline DSE, mean values of strain rate (-1.2 +/- 0.3 s(-1)) and strain (-17 +/- 8%) were not significantly different between both groups. In the ischaemic group, in the target region, strain at peak stress decreased to - 10 +/- 8%, whereas strain rate remained unchanged. In contrast, in the non-ischaemic group, strain at peak stress remained unchanged (-18 +/- 7%), whereas strain rate increased to - 2.5 +/- 1.1 s(-1). The receiver operating characteristic curve analysis revealed the change in strain rate as the best parameter to detect ischaemia, with a sensitivity of 89% and a specificity of 86%. In the remote region, in both groups, strain rate (-1.4 +/- 0.4 s(-1)) and strain values (-20 +/- 7%) were not significantly different at baseline, and strain rate doubled and strain remained unchanged at DSE peak stress. CONCLUSION: Non-invasive evaluation of regional deformation, using strain rate imaging during DSE, predicted the relevance of intermediate coronary stenosis. In this context, strain rate is superior to strain measurements for the quantification of the contractile reserve.

Fabry disease: guidelines for the evaluation and management of multi-organ system involvement.

Fabry disease is an X-linked metabolic storage disorder due to the deficiency of lysosomal alpha-galactosidase A, and the subsequent accumulation of glycosphingolipids, primarily globotriaosylceramide, throughout the body. Males with classical Fabry disease develop early symptoms including pain and hypohidrosis by the second decade of life reflecting disease progression in the peripheral and autonomic nervous systems. An insidious cascade of disease processes ultimately results in severe renal, cardiac, and central nervous system complications in adulthood. The late complications are the main cause of late morbidity, as well as premature mortality. Disease presentation in female heterozygotes may be as severe as in males although women may also remain asymptomatic. The recent introduction of enzyme replacement therapy to address the underlying pathophysiology of Fabry disease has focused attention on the need for comprehensive, multidisciplinary evaluation and management of the multi-organ system involvement. In anticipation of evidence-based recommendations, an international panel of physicians with expertise in Fabry disease has proposed guidelines for the recognition, evaluation, and surveillance of disease-associated morbidities, as well as therapeutic strategies, including enzyme replacement and other adjunctive therapies, to optimize patient outcomes.

How to distinguish between ischemic and nonischemic postsystolic thickening: a strain rate imaging study.

Ongoing myocardial thickening after aortic valve closure (postsystolic thickening = epsilonPST) is an established marker for the presence of segmental ischemia. However, epsilonPST may also be present in late activated segments and can be induced by pharmacological interventions or left ventricular pressure overload. The aim of this study was to determine if it is possible to distinguish between ischemic and nonischemic epsilonPST. In an experimental pig-model (n = 11) regional radial deformation was measured in the inferolateral wall during either normal perfusion or regional ischemia using ultrasonic strain rate imaging. Ischemia was induced by active hypoperfusion of the circumflex coronary artery territory. Measurements were made at 1. baseline, and during 2. theodrenalin infusion, 3. dobutamine infusion 4. esmolol infusion and 5. during a preload increase induced by saline infusion. In all segments where thickening was ongoing after aortic valve closure, the amount of epsilonPST was calculated as the difference of maximal strain minus systolic strain. In addition, peak strain rate during the isovolumetric relaxation period was extracted. During normal coronary perfusion, 73% of all segments (n = 40) developed epsilonPST. This physiological epsilonPST averaged 5 +/- 2% and was most frequently induced during the esmolol infusion (n = 11). Peak isovolumetric strain rate averaged -2.1 +/- 0.5 s(-1) in segments with physiological epsilonPST. During coronary hypoperfusion, 96% of the "at risk" segments developed epsilonPST. EpsilonPST in the ischemic segments averaged 14 +/- 3%, and was highest during the dobutamine infusion (25 +/- 4%) and lowest during the esmolol infusion (5 +/- 1%). In contrast to normally perfused segments, peak isovolumetric strain rate was positive in the ischemic segments and averaged 2.0 +/- 0.5 s(-1) in these pathologic segments with postsystolic strain. Using a cut-off value of > or = 0 s(-1) for isovolumetric strain rate, pathologic epsilonPST was detected with a sensitivity of 100% and a specificity of 87%. These experimental findings were confirmed by a subsequent clinical study with 6 patients with acute myocardial infarction (ischemic group) and 6 patients with arterial hypertension or aortic stenosis (nonischemic group). Ischemic and nonischemic postsystolic thickening can be precisely differentiated by extracting the polarity of the peak isovolumetric strain curve.

The variation of morphological and functional cardiac manifestation in Fabry disease: potential implications for the time course of the disease.

AIMS: The aim of this clinical cross-sectional study was to investigate the cardiac interrelation of morphological and functional abnormalities in patients with Fabry disease. METHODS AND RESULTS: Fifty-one patients (5-78 years) were compared with 25 controls (8-77 years). In all subjects, end-diastolic thickness of the left ventricle was measured by echocardiography and ultrasonic peak systolic strain rate (SR) was extracted to assess regional myocardial function. Magnetic resonance imaging was performed to assess late-enhancement for the detection of myocardial fibrosis in Fabry patients (n=39). In patients, women <20 years of age had no hypertrophy, no late-enhancement, and normal radial and longitudinal function (SR longitudinal=-1.7+/-0.5 s(-1); P=n.s. compared with controls). Ten women, >20 years of age, had no hypertrophy, no late-enhancement, normal radial and longitudinal function in the septal wall, but reduced longitudinal function in the lateral wall (SR=-1.4+/-0.5 s(-1)). All male patients without hypertrophy and no late-enhancement had normal radial function but reduced longitudinal function in both the septal and lateral walls (SR=-1.3+/-0.3 s(-1)). Patients with hypertrophy but without late-enhancement (n=13) had reduced radial and longitudinal function. Twelve patients displaying hypertrophy and late-enhancement had severely reduced radial and longitudinal function (SR=-1.1+/-0.5 s(-1)). Two of them with the worst impairment of regional function (SR=-0.8+/-0.6 s(-1)) died in the follow-up period. CONCLUSION: These results illustrate the variation of morphological changes and its functional consequences in Fabry cardiomyopathy.