Hans-Marc J. Siebelink

Regional myocardial blood flow reserve impairment and metabolic changes suggesting myocardial ischemia in patients with idiopathic dilated cardiomyopathy.

OBJECTIVES We performed positron emission tomography (PET) to evaluate myocardial ischemia in patients with idiopathic dilated cardiomyopathy (IDC). BACKGROUND Patients with IDC have anatomically normal coronary arteries, and it has been assumed that myocardial ischemia does not occur. METHODS We studied 22 patients with IDC and 22 control subjects using PET with nitrogen-13 ammonia to measure myocardial blood flow (MBF) at rest and during dipyridamole-induced hyperemia. To investigate glucose metabolism, fluorine-18 deoxyglucose (18FDG) was used. For imaging of oxygen consumption, carbon-11 acetate clearance rate constants (k(mono)) were assessed at rest and during submaximal dobutamine infusion (20 microg/kg body weight per min). RESULTS Global MBF reserve (dipyridamole-induced) was impaired in patients with IDC versus control subjects (1.7 +/- 0.21 vs. 2.7 +/- 0.10, p < 0.05). In patients with IDC, MBF reserve correlated with left ventricular (LV) systolic wall stress (r = -0.61, p = 0.01). Furthermore, in 16 of 22 patients with IDC (derived by dipyridamole perfusion) mismatch (decreased flow/increased 18FDG uptake) was observed in 17 +/- 8% of the myocardium. The extent of mismatch correlated with LV systolic wall stress (r = 0.64, p = 0.02). The MBF reserve was lower in the mismatch regions than in the normal regions (1.58 +/- 0.13 vs. 1.90 +/- 0.18, p < 0.05). During dobutamine infusion k(mono) was higher in the mismatch regions than in the normal regions (0.104 +/- 0.017 vs. 0.087 +/- 0.016 min(-1), p < 0.05). In the mismatch regions 18FDG uptake correlated negatively with rest k(mono) (r = -0.65, p < 0.05), suggesting a switch from aerobic to anaerobic metabolism. CONCLUSIONS Patients with IDC have a decreased MBF reserve. In addition, low MBF reserve was paralleled by high LV systolic wall stress. These global observations were associated with substantial myocardial mismatch areas showing the lowest MBF reserves. In geographically identical regions an abnormal oxygen consumption pattern was seen together with a switch from aerobic to anaerobic metabolism. These data support the notion that regional myocardial ischemia plays a role in IDC.

Comparison Between the Prognostic Value of Left Ventricular Function and Myocardial Perfusion Reserve in Patients with Ischemic Heart Disease

The purpose of this study was to compare the prognostic value of left ventricular ejection fraction (LVEF) and myocardial perfusion reserve (MPR) assessed with PET in patients with ischemic heart disease (IHD). Myocardial perfusion is the main determinant of left ventricular function in patients with IHD. The prognostic value of LVEF has been widely established. In addition, MPR determines survival in patients with hypertrophic and dilated cardiomyopathies. In the present study, we evaluated whether MPR also determines survival in patients with IHD. Methods: Between 1995 and 2003, 480 consecutive patients with chronic IHD underwent dipyridamole stress and rest 13N-ammonia PET to determine MPR. Additionally, 18F-FDG PET was performed for viability (mismatching defects), infarction (matching defects), and left ventricular function assessment. Patients were followed for all causes of mortality and major cardiovascular events. Results: In 463 of the 480 patients, valid MPR could be measured (368 men; mean age, 66 ± 11 y; LVEF, 35% ± 15%). One hundred nineteen patients underwent a PET-driven revascularization (67 through percutaneous coronary intervention and 52 through coronary artery bypass grafting). The remaining 344 patients were the subject of this study. The overall MPR was 1.71 ± 0.50 (intertertile boundaries, 1.49 and 1.84). After adjustment for age and sex, MPR was associated with a hazard ratio for cardiac death of 4.11 (95% confidence interval, 2.98–5.67) per SD decrease, whereas the risk for LVEF was 2.76 (2.00–3.82) per SD decrease. Conclusion: Patients with IHD with a low MPR are at high risk of cardiac death. MPR is a more sensitive predictor for cardiac death than is LVEF.

Head-to-head comparison of contrast-enhanced magnetic resonance imaging and electroanatomical voltage mapping to assess post-infarct scar characteristics in patients with ventricular tachycardias: real-time image integration and reversed registration

AIMS Substrate-based ablation of ventricular tachycardia (VT) relies on electroanatomical voltage mapping (EAVM). Integration of scar information from contrast-enhanced magnetic resonance imaging (CE-MRI) with EAVM may provide supplementary information. This study assessed the relation between electrogram voltages and CE-MRI scar characteristics using real-time integration and reversed registration. METHODS AND RESULTS Fifteen patients without implantable cardiac defibrillator (14 males, 64 ± 9 years) referred for VT ablation after myocardial infarction underwent CE-MRI. Contours of the CE-MRI were used to create three-dimensional surface meshes of the left ventricle (LV), aortic root, and left main stem (LM). Real-time integration of CE-MRI-derived scar meshes with EAVM of the LV and aortic root was performed using the LM and the CARTO surface registration algorithm. Merging of CE-MRI meshes with EAVM was successful with a registration error of 3.8 ± 0.6 mm. After the procedure, voltage amplitudes of each mapping point were superimposed on the corresponding CE-MRI location using the reversed registration matrix. Infarcts on CE-MRI were categorized by transmurality and signal intensity. Local bipolar and unipolar voltages decreased with increasing scar transmurality and were influenced by scar heterogeneity. Ventricular tachycardia reentry circuit isthmus sites were correlated to CE-MRI scar location. In three patients, VT isthmus sites were located in scar areas not identified by EAVM. CONCLUSION Integration of MRI-derived scar maps with EAVM during VT ablation is feasible and accurate. Contrast-enhanced magnetic resonance imaging identifies non-transmural scars and infarct grey zones not detected by EAVM according to the currently used voltage criteria and may provide important supplementary substrate information in selected patients.

Myocardial steatosis and biventricular strain and strain rate imaging in patients with type 2 diabetes mellitus.

Background— Magnetic resonance spectroscopy can quantify myocardial triglyceride content in type 2 diabetic patients. Its relation to alterations in left (LV) and right (RV) ventricular myocardial functions is unknown. Methods and Results— A total of 42 men with type 2 diabetes mellitus were recruited. Exclusion criteria included hemoglobin A1c >8.5%, known cardiovascular disease, diabetes-related complications, or blood pressure >150/85 mm Hg. Myocardial ischemia was excluded by a negative dobutamine stress test. LV and RV volumes and ejection fraction were quantified by magnetic resonance imaging. LV global longitudinal and RV free wall longitudinal strain, systolic strain rate, and diastolic strain rate were quantified by echocardiographic speckle tracking analyses. Myocardial triglyceride content was quantified by magnetic resonance spectroscopy and dichotomized on the basis of the median value of 0.76%. The median age was 59 years (25th and 75th percentiles, 54 and 62 years). Median diabetes diagnosis duration was 4 years, and median glycohemoglobin level was 6.2% (25th and 75th percentiles, 5.9% and 6.8%). There were no differences in LV and RV end-diastolic and end-systolic volume indexes and ejection fraction between patients with high (≥0.76%) and those with low (<0.76%) myocardial triglyceride content. However, patients with high myocardial triglyceride content had greater impairment of LV and RV myocardial strain and strain rate. The myocardial triglyceride content was an independent correlate of LV and RV longitudinal strain, systolic strain rate, and diastolic strain rate. Conclusions— High myocardial triglyceride content is associated with more pronounced impairment of LV and RV functions in men with uncomplicated type 2 diabetes mellitus.

Association between diffuse myocardial fibrosis by cardiac magnetic resonance contrast-enhanced T(1) mapping and subclinical myocardial dysfunction in diabetic patients: a pilot study.

Background— Diabetic patients have increased interstitial myocardial fibrosis on histological examination. Magnetic resonance imaging (MRI) T1 mapping is a previously validated imaging technique that can quantify the burden of global and regional interstitial fibrosis. However, the association between MRI T1 mapping and subtle left ventricular (LV) dysfunction in diabetic patients is unknown. Methods and Results— Fifty diabetic patients with normal LV ejection fraction (EF) and no underlying coronary artery disease or regional macroscopic scar on MRI delayed enhancement were prospectively recruited. Diabetic patients were compared with 19 healthy controls who were frequency matched in age, sex and body mass index. There were no significant differences in mean LV end-diastolic volume index, end-systolic volume index and LVEF between diabetic patients and healthy controls. Diabetic patients had significantly shorter global contrast-enhanced myocardial T1 time (425±72 ms vs. 504±34 ms, P<0.001). There was no correlation between global contrast-enhanced myocardial T1 time and LVEF (r=0.14, P=0.32) in the diabetic patients. However, there was good correlation between global contrast-enhanced myocardial T1 time and global longitudinal strain (r=−0.73, P<0.001). Global contrast-enhanced myocardial T1 time was the strongest independent determinant of global longitudinal strain on multivariate analysis (standardized &bgr;=−0.626, P<0.001). Similarly, there was good correlation between global contrast-enhanced myocardial T1 time and septal E′ (r=0.54, P<0.001). Global contrast-enhanced myocardial T1 time was also the strongest independent determinant of septal E′ (standardized &bgr;=0.432, P<0.001). Conclusions— A shorter global contrast-enhanced myocardial T1 time was associated with more impaired longitudinal myocardial systolic and diastolic function in diabetic patients.

Quantitative assessment of mitral regurgitation: comparison between three-dimensional transesophageal echocardiography and magnetic resonance imaging.

Background— Quantification of mitral regurgitation severity with 2-dimensional (2D) imaging techniques remains challenging. The present study compared the accuracy of 2D transesophageal echocardiography (TEE) and 3-dimensional (3D) TEE for quantification of mitral regurgitation, using MRI as the reference method. Methods and Results— Two-dimensional and 3D TEE and cardiac MRI were performed in 30 patients with mitral regurgitation. Mitral effective regurgitant orifice area (EROA) and regurgitant volume (Rvol) were estimated with 2D and 3D TEE. With 3D TEE, EROA was calculated using planimetry of the color Doppler flow from en face views and Rvol was derived by multiplying the EROA by the velocity time integral of the regurgitant jet. Finally, using MRI, mitral Rvol was quantified by subtracting the aortic flow volume from left ventricular stroke volume. Compared with 3D TEE, 2D TEE underestimated the EROA by a mean of 0.13 cm2. In addition, 2D TEE underestimated the Rvol by 21.6% when compared with 3D TEE and by 21.3% when compared with MRI. In contrast, 3D TEE underestimated the Rvol by only 1.2% when compared with MRI. Finally, one third of the patients in grade 1 and ≥50% of the patients in grade 2 and 3, as assessed with 2D TEE, would have been upgraded to a more severe grade, based on the 3D TEE and MRI measurements. Conclusions— Quantification of mitral EROA and Rvol with 3D TEE is feasible and accurate as compared with MRI and results in less underestimation of the Rvol as compared with 2D TEE.Background—Quantification of mitral regurgitation severity with 2-dimensional (2D) imaging techniques remains challenging. The present study compared the accuracy of 2D transesophageal echocardiography (TEE) and 3-dimensional (3D) TEE for quantification of mitral regurgitation, using MRI as the reference method. Methods and Results—Two-dimensional and 3D TEE and cardiac MRI were performed in 30 patients with mitral regurgitation. Mitral effective regurgitant orifice area (EROA) and regurgitant volume (Rvol) were estimated with 2D and 3D TEE. With 3D TEE, EROA was calculated using planimetry of the color Doppler flow from en face views and Rvol was derived by multiplying the EROA by the velocity time integral of the regurgitant jet. Finally, using MRI, mitral Rvol was quantified by subtracting the aortic flow volume from left ventricular stroke volume. Compared with 3D TEE, 2D TEE underestimated the EROA by a mean of 0.13 cm2. In addition, 2D TEE underestimated the Rvol by 21.6% when compared with 3D TEE and by 21.3% when compared with MRI. In contrast, 3D TEE underestimated the Rvol by only 1.2% when compared with MRI. Finally, one third of the patients in grade 1 and ≥50% of the patients in grade 2 and 3, as assessed with 2D TEE, would have been upgraded to a more severe grade, based on the 3D TEE and MRI measurements. Conclusions—Quantification of mitral EROA and Rvol with 3D TEE is feasible and accurate as compared with MRI and results in less underestimation of the Rvol as compared with 2D TEE.

Epicardial substrate mapping for ventricular tachycardia ablation in patients with non-ischaemic cardiomyopathy: a new algorithm to differentiate between scar and viable myocardium developed by simultaneous integration of computed tomography and contrast-enhanced magnetic resonance imaging.

AIMS During epicardial electroanatomical mapping (EAM), it is difficult to differentiate between fibrosis and fat, as both exhibit attenuated bipolar voltage (BV). The purpose of this study was to assess whether unipolar voltage (UV), BV, and electrogram characteristics (EC) can distinguish fibrosis from viable myocardium and fat during epicardial EAM for ventricular tachycardia (VT) ablation in non-ischaemic cardiomyopathy (NICM). METHODS AND RESULTS Ten NICM patients (7 males, 56 ± 13 years) with VT underwent epicardial EAM with real-time integration of computed tomography-derived epicardial fat and contrast-enhanced MRI-derived scar. Bipolar voltage (filtered 30-400 Hz), UV (filtered 1-240 Hz), and EC (duration and morphology) were correlated with the presence of fat and scar. At sites devoid of fat, the optimal cutoff values to differentiate between scar and myocardium were 1.81 mV for BV and 7.95 mV for UV. Bipolar voltage, UV, and electrogram duration >50 ms distinguished scar from myocardium in areas covered with <2.8 mm fat (all P < 0.001), but not ≥ 2.8 mm fat. In contrast, electrogram morphology-characteristics could also detect scar covered with ≥ 2.8 mm fat (P = 0.001). A newly developed three-step algorithm combining electrogram morphology, duration, and UV could correctly identify scar with a sensitivity of 75%. Unipolar voltage but not BV could detect intramural scar in the absence of fat. CONCLUSIONS Both BV ≤ 1.81 mV and UV ≤ 7.95 mV are useful for detection of scar during epicardial EAM, in the absence of ≥ 2.8 mm fat. However, EC can be used to detect scar covered with fat. A newly developed algorithm combining UV and EC can differentiate between scar and viable myocardium. Unipolar voltage but not BV could detect intramural scar.

Reduced Left Ventricular Torsion Early After Myocardial Infarction Is Related to Left Ventricular Remodeling

Background—Left ventricular (LV) torsion is emerging as a sensitive parameter of LV systolic myocardial performance. The aim of the present study was to explore the effects of acute myocardial infarction (AMI) on LV torsion and to determine the value of LV torsion early after AMI in predicting LV remodeling at 6-month follow-up. Methods and Results—A total of 120 patients with a first ST-segment elevation AMI (mean±SD age, 59±10 years; 73% male) were included. All patients underwent primary percutaneous coronary intervention. After 48 hours, speckle-tracking echocardiography was performed to assess LV torsion; infarct size was assessed by myocardial contrast echocardiography. At 6-month follow-up, LV volumes and LV ejection fraction were reassessed to identity patients with LV remodeling (defined as a ≥15% increase in LV end-systolic volume). Compared with control subjects, peak LV torsion in AMI patients was significantly impaired (1.54±0.64°/cm vs 2.07±0.27°/cm, P<0.001). By multivariate analysis, only LV ejection fraction (&bgr;=0.36, P<0.001) and infarct size (&bgr;=−0.47, P<0.001) were independently associated with peak LV torsion. At 6-month follow-up, 19 patients showed LV remodeling. By multivariate analysis, only peak LV torsion (odds ratio=0.77; 95% CI, 0.65–0.92; P=0.003) and infarct size (odds ratio=1.04; 95% CI, 1.01–1.07; P=0.021) were independently related to LV remodeling. Peak LV torsion provided modest but significant incremental value over clinical, echocardiographic, and myocardial contrast echocardiography variables in predicting LV remodeling. By receiver-operating characteristics curve analysis, peak LV torsion ≤1.44°/cm provided the highest sensitivity (95%) and specificity (77%) to predict LV remodeling. Conclusions—LV torsion is significantly impaired early after AMI. The amount of impairment of LV torsion predicts LV remodeling at 6-month follow-up.

Positive remodeling on coronary computed tomography as a marker for plaque vulnerability on virtual histology intravascular ultrasound.

Coronary computed tomographic angiography allows direct evaluation of the vessel wall and thus positive remodeling, which is a marker of vulnerability. The purpose of this study was to assess the association between positive remodeling on computed tomography angiogram (CTA) and vulnerable plaque characteristics on virtual histologic intravascular ultrasound (VH IVUS) images. Forty-five patients (78% men, 58 ± 11 years old) underwent computed tomographic angiography followed by VH IVUS. On CTA, the remodeling index was determined for each lesion by a blinded observer using quantitative analysis. Positive remodeling was defined based on a remodeling index ≥1.0. Percent necrotic core and presence of thin-capped fibroatheroma (TCFA) were used as markers for plaque vulnerability on VH IVUS images. Ninety-nine atherosclerotic plaques were evaluated, of which 37 lesions (37.4%) were identified as having positive remodeling on CTA. Higher levels of plaque vulnerability were identified in lesions with positive remodeling compared to lesions without positive remodeling. Percent necrotic core was significantly higher in lesions with positive remodeling (15.7 ± 7.8%) compared to lesions without this characteristic (10.2 ± 7.2%, p <0.001). Furthermore, significantly more TCFA lesions were identified in positively remodeled lesions (n = 16, 43.2%) than in lesions without positive remodeling (n = 3, 4.8%, p <0.001). In conclusion, lesions with positive remodeling on CTA are associated with increased levels of plaque vulnerability on VH IVUS images including a higher percent necrotic core and a higher prevalence of TCFA. Thus evaluation of remodeling on CTA may provide a valuable marker for plaque vulnerability.

Accuracy of Three-Dimensional Versus Two-Dimensional Echocardiography for Quantification of Aortic Regurgitation and Validation by Three-Dimensional Three-Directional Velocity-Encoded Magnetic Resonance Imaging

Quantitative assessment of aortic regurgitation (AR) remains challenging. The present study evaluated the accuracy of 2-dimensional (2D) and 3-dimensional (3D) transthoracic echocardiography (TTE) for AR quantification, using 3D 3-directional velocity-encoded magnetic resonance imaging (VE-MRI) as the reference method. Thirty-two AR patients were included. With color Doppler TTE, 2D effective regurgitant orifice area (EROA) was calculated using the proximal isovelocity surface area method. From the 3D TTE multiplanar reformation data, 3D-EROA was calculated by planimetry of the vena contracta. Regurgitant volumes (RVol) were obtained by multiplying the 2D-EROA and 3D-EROA by the velocity-time integral of AR jet and compared with that obtained using VE-MRI. For the entire population, 3D TTE RVol demonstrated a strong correlation and good agreement with VE-MRI RVol (r = 0.94 and -13.6 to 15.6 ml/beat, respectively), whereas 2D TTE RVol showed a modest correlation and large limits of agreement with VE-MRI (r = 0.70 and -22.2 to 32.8 ml/beat, respectively). Eccentric jets were noted in 16 patients (50%). In these patients, 3D TTE demonstrated an excellent correlation (r = 0.95) with VE-MRI, a small bias (0.1 ml/beat) and narrow limits of agreement (-18.7 to 18.8 ml/beat). Finally, the kappa agreement between 3D TTE and VE-MRI for grading of AR severity was good (k = 0.96), whereas the kappa agreement between 2D TTE and VE-MRI was suboptimal (k = 0.53). In conclusion, AR RVol quantification using 3D TTE is accurate, and its advantage over 2D TTE is particularly evident in patients with eccentric jets.