Joern Sandstede

Improvement of Cardiac Function During Enzyme Replacement Therapy in Patients With Fabry Disease A Prospective Strain Rate Imaging Study

Background—Enzyme replacement therapy (ERT) has been shown to enhance microvascular endothelial globotriaosylceramide clearance in the hearts of patients with Fabry disease. Whether these results can be translated into an improvement of myocardial function has yet to be demonstrated. Methods and Results—Sixteen patients with Fabry disease who were treated in an open-label study with 1.0 mg/kg body weight of recombinant &agr;-Gal A (agalsidase &bgr;, Fabrazyme) were followed up for 12 months. Myocardial function was quantified by ultrasonic strain rate imaging to assess radial and longitudinal myocardial deformation. End-diastolic thickness of the left ventricular posterior wall and myocardial mass (assessed by magnetic resonance imaging, n=10) was measured at baseline and after 12 months of ERT. Data were compared with 16 age-matched healthy controls. At baseline, both peak systolic strain rate and systolic strain were significantly reduced in the radial and longitudinal direction in patients compared with controls. Peak systolic strain rate increased significantly in the posterior wall (radial function) after one year of treatment (baseline, 2.8±0.2 s−1; 12 months, 3.7±0.3 s−1; P <0.05). In addition, end-systolic strain of the posterior wall increased significantly (baseline, 34±3%; 12 months, 45±4%; P <0.05). This enhancement in radial function was accompanied by an improvement in longitudinal function. End-diastolic thickness of the posterior wall decreased significantly after 12 months of treatment (baseline, 13.8±0.6 mm; 12 months, 11.8±0.6 mm; P <0.05). In parallel, myocardial mass decreased significantly from 201±18 to 180±21 g (P <0.05). Conclusions—These results suggest that ERT can decrease left ventricular hypertrophy and improve regional myocardial function.

Detection of myocardial viability by low-dose dobutamine Cine MR imaging.

The purpose of this work was to test the diagnostic value of dobutamine stress magnetic resonance imaging (MRI) for predicting recovery of regional myocardial contractility after revascularization. Cardiac wall motion abnormalities are due to either non-viable and/or scarred, or viable, but hibernating, myocardial tissue. Dobutamine stress leads to increased systolic wall thickening only in viable myocardium. Twenty-five patients with akinetic or dyskinetic myocardial regions were examined with a Cine FLASH-2D sequence at rest and during dobutamine stress (10 microg/kg/min). Patients were re-examined at rest 3, and in case of persisting wall motion defects, 6 months after revascularization. Criterion of viability was increasing end-systolic wall thickening during stress and/or at follow-up. Akinetic regions related either to the LAD (n = 19) or to the RCA (n = 6) were judged viable if > or = 50% of the affected segments improved. MR studies were completed in all subjects without arrhythmia or need for early terminations due to symptoms. Sensitivity, specificity, and positive predictive value for the prediction of myocardial viability were 61%, 90%, and 87% for the segment-related analysis, and 76%, 100%, and 100% for the patient-related analysis based on coronary artery distribution, respectively. Dobutamine stress MRI allows to predict global functional recovery of akinetic myocardial regions after revascularization with a high positive predictive value and high specificity.

Time course of 23Na signal intensity after myocardial infarction in humans

Experimental studies demonstrated persistently increased 23Na content in nonviable myocardium post‐myocardial infarction (MI). We hypothesized that nonviable myocardium in humans would show elevated 23Na content at all stages of infarct development, and therefore could be imaged with 23Na MRI. Ten patients were examined on days 4, 14, and 90 after infarction, and five of these patients participated in a 12‐month follow‐up. Double angulated short‐axis cardiac 23Na images were obtained with the use of a 23Na surface coil and an ECG‐triggered, 3D gradient‐echo sequence. 1H T2‐weighted imaging (N = 9) was performed on days 4, 14, and 90. Wall motion was assessed by cine MRI, and the infarct size was determined by late enhancement on day 90. The 23Na signal intensity (SI) of infarcted myocardium was expressed as the percentage increase over 23Na SI of noninfarcted myocardium. All of the patients showed an area of elevated SI on 23Na and 1H T2‐weighted images that correlated with wall motion abnormalities and late enhancement. 23Na SI was highest on day 4. It then decreased until day 90, but remained elevated (39% ± 18%, 31% ± 17%, 28% ± 13% on days 4, 14, and 90, respectively, P = 0.001). No further decrease was found 1 year after infarction (25% ± 7%, P = 0.89 vs. day 90). 1H T2‐weighted SI decreased between days 4 and 14, but on day 90 only six of nine patients had a residual elevated SI. Thus, 23Na SI is elevated in nonviable infarction at all time points following MI, and 23Na MRI may become a suitable technique for imaging nonviable myocardium in humans. Magn Reson Med 52:545–551, 2004.

Optimization of ECG-triggered 3D 23Na MRI of the human heart

23Na MRI may allow distinction of normal and ischemically injured myocardium. The aim of this study was to optimize 23Na MRI of the human heart by improvement of spatial resolution and ECG‐triggering and to measure the signal/noise of blood and myocardium and the myocardium/blood signal ratios in a volunteer study. A spoiled gradient echo sequence was developed on a 1.5T scanner equipped with a 23Na heart surface coil. 3D short axis ECG‐triggered 23Na MRI was performed in 10 healthy subjects. The signal/noise of myocardium and blood were 8.2 ± 0.7 and 18.3 ± 1.3, respectively, signal ratio myocardium/blood was 0.44 ± 0.03. This value is in good agreement with the theoretical value of 0.45. ECG gated 3D 23Na MRI of the human heart is feasible with sufficient spatial resolution and signal/noise ratio. Magn Reson Med 45:164–166, 2001.

Breath-hold 3D MR coronary angiography with a new intravascular contrast agent (feruglose)—first clinical experiences

Demonstration of the initial results of breath-hold 3D MR coronary angiography with patients using a new intravascular contrast agent (feruglose). Contrast-enhanced 3D MR-coronary angiography was performed in 5 patients with coronary artery disease after administration of feruglose in three different doses (0.5 (n = 3), 2, 5 mg Fe/kg body weight for each patient). MR coronary angiography was performed with an ECG-triggered 3D-FLASH-sequence during breath-hold at 1.5 T (TR 6.8 ms, TE 2.5 ms, flip-angle 30 degrees ). To reduce data acquisition time, only the two anterior elements of the phased-array body coil were activated. The data acquisition window within the cardiac cycle ranged between 217-326 ms depending on the matrix. Signal-to-noise (SNR) and contrast-to-noise ratios (CNR) of the coronary arteries were analyzed, and the results for the detection of coronary artery stenoses were compared with those obtained by conventional coronary angiography. SNR and CNR revealed an improved image quality at a dose of 2 mg Fe/kg compared with the lower dose, but no further improvement was obtained by rising the dose to 5 mg Fe/kg. Except for the left circumflex artery of one patient, at minimum the proximal parts of all four main coronary arteries could be imaged for all patients. Within the visible parts of the coronary arteries, six of eight significant coronary stenoses were identified correctly. Imaging of the proximal parts of the coronary arteries including detection of stenoses is possible during breath-hold using an intravascular contrast agent.

Cine MR imaging after myocardial infarction--assessment and follow-up of regional and global left ventricular function.

Myocardial infarction often leads to regional wall motion defects and in case of large defects to remodeling of the left ventricle. With this study, changes in regional and global myocardial function of 12 patients 3 weeks after myocardial infarction and after revascularization therapy were determined using MRI. Cine MRI was performed at study entry at rest and during low-dose dobutamine stimulation. All patients were re-examined at rest 3 and 6 months after the revascularization, including analysis of wall thickening and of left ventricular end-diastolic volume index (LVEDVI), end-systolic volume index (LVESVI), ejection fraction (LVEF), and mass index. After revascularization, 6 patients with stress-induced improvement of regional wall thickening recovered, 4 patients without improvement did not, but 2 patients without stress-induced improvement of wall thickening also recovered. Concerning global cardiac function, patients with mainly improved regional wall motion also showed a lower LVESVI and a higher LVEF than patients without improvement of regional contractility 6 months after revascularization in comparison to study entry. In conclusion, improvement of global myocardial function after revascularization is higher in patients with improved contractility in the infarcted region. The extent of the response of regions with wall motion defects to dobutamine stress correlates with the actual improvement after revascularization, and, therefore, dobutamine stress MRI may be helpful in selecting patients that will have a higher benefit from a revascularization therapy.

Time course of contrast enhancement patterns after Gd-BOPTA in correlation to myocardial infarction and viability: a feasibility study.

Our objective was to analyze contrast enhancement patterns (CEP) and their time course after myocardial infarction (MI) following injection of Gd‐BOPTA in correlation with recovery of regional function. Seven patients with subacute MI (18 ± nine days) were examined before, as well as three and six (n = six) months after, revascularization of the infarct‐related artery. Regional wall motion abnormalities were assessed by cine‐MRI, and repetitive images of one representative slice were acquired up to 45 minutes after 0.05 mmol/kg Gd‐BOPTA using a T1‐w TSE‐sequence. Two patients showed mid‐wall/subendocardial, one patient subendocardial enhancement of MI associated with mechanical improvement after revascularization. Three patients without improvement revealed a mid‐wall hypoenhanced zone within the first five minutes after injection, which was unchanged at follow‐up. One patient with partial functional improvement showed transmural enhancement and a mid‐wall hypoenhanced zone in adjacent areas. With this feasibility study, we concluded that mid‐wall and/or subendocardial enhancement after Gd‐BOPTA was associated with viable myocardium, whereas detection of microvascular obstruction correlating with scar formation is suggested by mid‐wall hypoenhancement within the first five minutes after injection. J. Magn. Reson. Imaging 2001;14:789–794.

Detection of myocardial infarctions by acquisition-weighted 31P-MR spectroscopy in humans.

To determine whether the recently applied technique of acquisition‐weighted 31P‐MR spectroscopy (AW‐MRS) allows for the detection of depressed energy metabolism in patients with inferior wall myocardial infarctions.

Sodium T2* relaxation times in human heart muscle

To determine sodium transverse relaxation (T2*) characteristics for myocardium, blood and cartilage in humans.

Evaluation of sodium T1 relaxation times in human heart

To evaluate the sodium longitudinal relaxation (T1) characteristics for myocardium and blood in humans.