Willem G. van Dockum

Delayed contrast-enhanced magnetic resonance imaging for the prediction of regional functional improvement after acute myocardial infarction.

OBJECTIVES We evaluated whether delayed contrast-enhanced magnetic resonance imaging (DCE-MRI) using an extracellular contrast agent could predict improvement of dysfunctional but viable myocardium after acute reperfused myocardial infarction (MI). BACKGROUND The transmural extent of hyperenhancement at DCE-MRI has been related to improvement of function in reperfused MI. However, evidence is still limited, and earlier reports have produced conflicting results regarding the significance of contrast patterns after infarction. METHODS Thirty patients (mean age 59 +/- 11 years, 27 males) underwent cine MRI and DCE-MRI 7 +/- 3 days after a first reperfused acute MI and follow-up cine MRI at 13 +/- 3 weeks. Segmental wall thickening and segmental extent of hyperenhancement were scored in 1,689 segments. RESULTS Of 500 dysfunctional segments, 273 (55%) improved at follow-up. There was no difference in likelihood of improvement or complete functional recovery between segments with 0% and 1% to 25% hyperenhancement. The likelihood of improvement of segments without hyperenhancement was 2.9, 14.3, and 20 times higher than that of segments with 26% to 50%, 51% to 75%, and >75% hyperenhancement, respectively (p < 0.001). The likelihood of complete functional recovery of segments without hyperenhancement was 3.8, 11.1, and 50 times higher than that of segments with 26% to 50%, 51% to 75%, and >75% hyperenhancement, respectively (p < 0.001). CONCLUSIONS In patients with recent reperfused MI, functional improvement of stunned myocardium is predicted by DCE-MRI.

Early Onset and Progression of Left Ventricular Remodeling After Alcohol Septal Ablation in Hypertrophic Obstructive Cardiomyopathy

Background—Alcohol septal ablation (ASA) reduces left ventricular outflow tract (LVOT) pressure gradient in patients with hypertrophic obstructive cardiomyopathy (HOCM), which leads to left ventricular remodeling. We sought to describe the early to midterm changes and modulating factors of the remodeling process using cardiac MRI (CMR). Methods and Results—CMR was performed at baseline and 1 and 6 months after ASA in 29 patients with HOCM (age 52±16 years). Contrast-enhanced CMR showed no infarct-related hyperenhancement outside the target septal area. Septal mass decreased from 75±23 g at baseline to 68±22 and 58±19 g (P<0.001) at 1- and 6-month follow-up, respectively. Remote, nonseptal mass decreased from 141±41 to 132±40 and 111±27 g (P<0.001), respectively. Analysis of temporal trends revealed that septal mass reduction was positively associated with contrast-enhanced infarct size and transmural or left-sided septal infarct location at both 1 and 6 months. Remote mass reduction was associated with infarct location at 6 months but not with contrast-enhanced infarct size. By linear regression analysis, percentage remote mass reduction correlated significantly with LVOT gradient reduction at 6-month follow-up (P=0.03). Conclusions—Left ventricular remodeling after ASA occurs early and progresses on midterm follow-up, modulated by CMR infarct size and location. Remote mass reduction is associated with infarct location and correlates with reduction of the LVOT pressure gradient. Thus, myocardial hypertrophy in HOCM is, at least in part, afterload dependent and reversible and is not exclusively caused by the genetic disorder.

Variable clinical manifestation of a novel missense mutation in the alpha-tropomyosin (TPM1) gene in familial hypertrophic cardiomyopathy

OBJECTIVES This study was initiated to identify the disease-causing genetic defect in a family with hypertrophic cardiomyopathy (HCM) and high incidence of sudden death. BACKGROUND Familial hypertropic cardiomyopathy (FHC) is an autosomal dominant transmitted disorder that is genetically and clinically heterogeneous. Mutations in 11 genes have been associated with the pathogenesis of the disease. METHODS We studied a large FHC family, first by linkage analysis, to identify the gene involved, and subsequently screened the gene, encoding alpha-tropomyosin (TPM1), for mutations by using single-strand conformation polymorphism and sequencing analysis. RESULTS Twelve family members presented clinical features of HCM, five of whom died at young age, while others had only mild clinical features. Marker analysis showed linkage for the TPM1 gene on chromosome 15q22 (maximal logarithm of the odds score is 5.16, theta = 0); subsequently, a novel missense mutation (Glu62Gln) was identified. CONCLUSIONS The novel mutation identified in TPM1 is associated with the clinical features of cardiac hypertrophy in all but one genetically affected member of this large family. The clinical data suggest a malignant phenotype at young age with a variable clinical manifestation and penetrance at older age. The Glu62Gln mutation is the sixth TPM1 mutation identified as the cause of FHC, indicating that mutations in this gene are very rare. This is the first reported amino acid substitution at the f-position within the coiled-coil structure of the tropomyosin protein.

Functional Outcome after Revascularization in Patients with Chronic Ischemic Heart Disease: A Quantitative Late Gadolinium Enhancement CMR Study Evaluating Transmural Scar Extent, Wall Thickness and Periprocedural Necrosis

In patients with chronic ischemic myocardial dysfunction, late gadolinium enhancement CMR (LGE-CMR) accurately depicts the regional extent of fibrosis and predicts functional recovery after revascularization. We hypothesized that the predictive accuracy of LGE-CMR could be optimized by not only taking into account the transmural extent of hyperenhancement but also the amount of residual, non-enhanced viable myocardium, and procedure related necrosis. We studied 45 patients with chronic ischemic left ventricular dysfunction, who underwent cine and LGE-CMR 1 month before and 3 months after surgical or percutaneous revascularization. Segmental and global function, scar, presence of a significant residual viable rim (defined as >or=4.5 mm), and procedure related necrosis were fully quantified using standardized methods and objective thresholds. Sixty percent of segments without hyperenhancement showed functional improvement at follow-up. No improvement was observed in segments with >75% segmental extent of hyperenhancement (SEH), while segments with 1-25%, 26-50%, and 51-75% SEH were 4, 8, and 20 times less likely to improve (multilevel analysis, p<0.001). Thickness of the viable rim largely paralleled total wall thickness; therefore, the presence of a significant viable rim did not provide additional diagnostic value beyond SEH. Procedure related necrosis was found in 12 (27%) patients. The presence of procedure related necrosis was the only (negative) predictor of changes in left ventricular volumes and ejection fraction. In conclusion, we found that functional outcome after revascularization was influenced by both transmural extent of hyperenhancement and procedure related necrosis. However, the presence of a significant residual, viable rim was of no additional diagnostic value.

Accuracy of One‐ and Two‐Dimensional Algorithms with Optimal Image Plane Position for the Estimation of Left Ventricular Mass: A Comparative Study Using Magnetic Resonance Imaging

The commonly recommended one-dimensional (ID) and two-dimensional (2D) algorithms for left ventricular (LV) mass calculation are limited by assumptions about ventricular geometry and image plane position. To assess the accuracy of these algorithms after eliminating errors associated with image plane position, LV mass was calculated from high quality cardiovascular magnetic resonance imaging (CMR) data sets using ID (modified cube formula; MCF) and 2D algorithms [area-length (AL) and truncated ellipsoid (TE) methods], and the summation of slices (SS) method as reference technique in 25 patients with LV aneurysms, 15 patients with hypertrophic cardiomyopathy, and 10 healthy subjects. Each algorithm in each group overestimated LV mass compared to SS (p <0.05 and p<0.001). In each patient group, the smallest bias to the reference method was observed for the TE algorithm (p<0.001 vs. MCF and p < 0.05 vs. AL). The LV mass interval encompassing the limits of agreement was 120-220 g for MCF, 100-148 g for AL, and 80-136 g for TE. The interstudy reproducibility of the SS technique for the assessment of LV mass was superior compared to the ID and 2D algorithms. We conclude that despite the use of optimized image plane position ID and 2D algorithms are inaccurate for calculation of LV mass in ventricles with normal and distorted LV geometry. Thus, 3D imaging techniques, such as CMR, should be preferred when assessing LV mass.