Ingo Paetsch

Magnetic resonance perfusion measurements for the noninvasive detection of coronary artery disease

Background—With MRI, an index of myocardial perfusion reserve (MPRI) can be determined. We assessed the value of this technique for the noninvasive detection of coronary artery disease (CAD) in patients with suspected CAD. Methods and Results—Eighty-four patients referred for a primary diagnostic coronary angiography were examined with a 1.5 T MRI tomograph (Philips-ACS). For each heartbeat, 5 slices were acquired during the first pass of 0.025 mmol gadolinium-diethylenetriamine pentaacetic acid/kg body weight before and during adenosine vasodilation by using a turbo-gradient echo/echo-planar imaging-hybrid sequence. MPRI was determined from the alteration of the upslope of the myocardial signal intensity curves for 6 equiangular segments per slice. Receiver operating characteristics were performed for different criteria to differentiate ischemic and nonischemic segments. Prevalence of CAD was 51%. Best results were achieved when only the 3 inner slices were assessed and a threshold value of 1.1 was used for the second smallest value as a marker for significant CAD. This approach yielded a sensitivity of 88%, specificity of 90%, and accuracy of 89%. Conclusion—The determination of MPRI with MRI yields a high diagnostic accuracy in patients with suspected CAD.

Prognostic Value of Cardiac Magnetic Resonance Stress Tests Adenosine Stress Perfusion and Dobutamine Stress Wall Motion Imaging

Background— Adenosine stress magnetic resonance perfusion (MRP) and dobutamine stress magnetic resonance (DSMR) wall motion analyses are highly accurate for the detection of myocardial ischemia. However, knowledge about the prognostic value of stress MR examinations is limited. We sought to determine the value of MRP and DSMR, as assessed during a single-session examination, in predicting the outcome of patients with known or suspected coronary artery disease. Methods and Results— In 513 patients (with known or suspected coronary disease, prior coronary artery bypass graft, or percutaneous coronary intervention), a combined single-session magnetic resonance stress examination (MRP and DSMR) was performed at 1.5 T. For first-pass perfusion imaging, the standard adenosine stress imaging protocol (140 &mgr;g · kg−1 · min−1 for 6 minutes, 3-slice turbo field echo-echo-planar imaging or steady-state free precession sequence, 0.05 mmol/kg Gd-DTPA) was applied, and for DSMR, the standard high-dose dobutamine/atropine protocol (steady-state free-precession cine sequence) was applied. Stress testing was classified as pathological if at MRP ≥1 segment showed an inducible perfusion deficit >25% transmurality or if at DSMR ≥1 segment showed an inducible wall motion abnormality. During a median follow-up of 2.3 years (range, 0.06 to 4.55 years), 19 cardiac events occurred (4.1%; 9 cardiac deaths, 10 nonfatal myocardial infarctions). The 3-year event-free survival was 99.2% for patients with normal MRP and DSMR and 83.5% for those with abnormal MRP and DSMR. Univariate analysis showed ischemia identified by MRP and DSMR to be predictive of cardiac events (hazard ratio, 12.51; 95% confidence interval, 3.64 to 43.03; and hazard ratio, 5.42; 95% confidence interval, 2.18 to 13.50; P<0.001, respectively); other predictors were diabetes mellitus, known coronary artery disease, and the presence of resting wall motion abnormality. By multivariate analysis, ischemia on magnetic resonance stress testing (MRP or DSMR) was an independent predictor of cardiac events. In a stepwise multivariate model (Cox regression), an abnormal magnetic resonance stress test result had significant incremental value over clinical risk factors and resting wall motion abnormality (P<0.001). Conclusions— In patients with known or suspected coronary artery disease, myocardial ischemia detected by MRP and DSMR can be used to identify patients at high risk for subsequent cardiac death or nonfatal myocardial infarction. For patients with normal MRP and DSMR, the 3-year event-free survival was 99.2%. MR stress testing provides important incremental information over clinical risk factors and resting wall motion abnormalities.

Comparison of Dobutamine Stress Magnetic Resonance, Adenosine Stress Magnetic Resonance, and Adenosine Stress Magnetic Resonance Perfusion

Background—Dobutamine stress MR (DSMR) is highly accurate for the detection of inducible wall motion abnormalities (IWMAs). Adenosine has a more favorable safety profile and is well established for the assessment of myocardial perfusion. We evaluated the diagnostic value of IWMAs during dobutamine and adenosine stress MR and adenosine MR perfusion compared with invasive coronary angiography. Methods and Results—Seventy-nine consecutive patients (suspected or known coronary disease, no history of prior myocardial infarction) scheduled for cardiac catheterization underwent cardiac MR (1.5 T). After 4 minutes of adenosine infusion (140 &mgr;g · kg−1 · min−1 for 6 minutes), wall motion was assessed (steady-state free precession), and subsequently perfusion scans (3-slice turbo field echo-echo planar imaging; 0.05 mmol/kg Gd-BOPTA) were performed. After a 15-minute break, rest perfusion was imaged, followed by standard DSMR/atropine stress MR. Wall motion was classified as pathological if ≥1 segment showed IWMAs. The transmural extent of inducible perfusion deficits (<25%, 25% to 50%, 51% to 75%, and >75%) was used to grade segmental perfusion. Quantitative coronary angiography was performed with significant stenosis defined as >50% diameter stenosis. Fifty-three patients (67%) had coronary artery stenoses >50%; sensitivity and specificity for detection by dobutamine and adenosine stress and adenosine perfusion were 89% and 80%, 40% and 96%, and 91% and 62%, respectively. Adenosine IWMAs were seen only in segments with >75% transmural perfusion deficit. Conclusions—DSMR is superior to adenosine stress for the induction of IWMAs in patients with significant coronary artery disease. Visual assessment of adenosine stress perfusion is sensitive with a low specificity, whereas adenosine stress MR wall motion is highly specific because it identifies only patients with high-grade perfusion deficits. Thus, DSMR is the method of choice for current state-of-the-art treatment regimens to detect ischemia in patients with suspected or known coronary artery disease but no history of prior myocardial infarction.

Angiotensin II Type 2 Receptor Stimulation A Novel Option of Therapeutic Interference With the Renin-Angiotensin System in Myocardial Infarction?

Background— This study is the first to examine the effect of direct angiotensin II type 2 (AT2) receptor stimulation on postinfarct cardiac function with the use of the novel nonpeptide AT2 receptor agonist compound 21 (C21). Methods and Results— Myocardial infarction (MI) was induced in Wistar rats by permanent ligation of the left coronary artery. Treatment with C21 (0.01, 0.03, 0.3 mg/kg per day IP) was started 24 hours after MI and was continued until euthanasia (7 days after MI). Infarct size was assessed by magnetic resonance imaging, and hemodynamic measurements were performed via transthoracic Doppler echocardiography and intracardiac Millar catheter. Cardiac tissues were analyzed for inflammation and apoptosis markers with immunoblotting and real-time reverse transcription polymerase chain reaction. C21 significantly improved systolic and diastolic ventricular function. Scar size was smallest in the C21-treated rats. In regard to underlying mechanisms, C21 diminished MI-induced Fas-ligand and caspase-3 expression in the peri-infarct zone, indicating an antiapoptotic effect. Phosphorylation of the p44/42 and p38 mitogen-activated protein kinases, both involved in the regulation of cell survival, was strongly reduced after MI but almost completely rescued by C21 treatment. Furthermore, C21 decreased MI-induced serum monocyte chemoattractant protein-1 and myeloperoxidase as well as cardiac interleukin-6, interleukin-1&bgr;, and interleukin-2 expression, suggesting an antiinflammatory effect. Conclusions— Direct AT2 receptor stimulation may be a novel therapeutic approach to improve post-MI systolic and diastolic function by antiapoptotic and antiinflammatory mechanisms.

Improvement of myocardial perfusion reserve early after coronary intervention: assessment with cardiac magnetic resonance imaging

OBJECTIVES The purpose of this study was to determine the potential value of magnetic resonance myocardial perfusion in the follow-up of patients after coronary intervention. BACKGROUND In some patients a residual impairment of myocardial perfusion reserve (MPR) early after successful coronary intervention has been observed. In this study we evaluated an MPR index before and after intervention with magnetic resonance. METHODS Thirty-five patients with single- and multivessel coronary artery disease were studied before and 24 h after intervention. The signal intensity time curves of the first pass of a gadolinium-diethylene triamine pentacetic acid bolus injected via a central vein catheter were evaluated before and after dipyridamole infusion. The upslope was determined using a linear fit. Myocardial perfusion reserve index was estimated from the alterations of the upslope. RESULTS The MPR index in segments perfused by the stenotic artery was significantly lower than in the control segments (1.07 +/- 0.24 vs. 2.18 +/- 0.35, p < 0.001) and improved significantly after intervention (1.89 +/- 0.39, p < 0.001) but did not normalize completely (p < 0.01). After intervention the MPR index remained significantly lower in the balloon percutaneous transluminal coronary angioplasty group (1.72 +/- 0.38; n = 13) in comparison with the stent group (1.99 +/- 0.36, n = 18, p < 0.05). In the stent group a complete normalization of the MPR index was found 24 h after stenting. CONCLUSIONS Magnetic resonance perfusion measurements allow a reliable assessment of MPR index. An improvement of MPR index can be observed after coronary intervention, which is more pronounced after stenting. Magnetic resonance perfusion measurements allow the assessment and may be useful for the follow-up of patients with coronary artery disease after coronary intervention.

Improved Accuracy of Quantitative Assessment of Left Ventricular Volume and Ejection Fraction by Geometric Models with Steady-State Free Precession

The purpose of this study was to determine whether steady-state free precession (SSFP) could improve accuracy of geometric models for evaluation of left ventricular (LV) function in comparison to turbo gradient echo (TGrE) and thereby reduce the acquisition and post-processing times, which are commonly long by use of the Simpsons Rule. In 25 subjects, cine loops of the complete heart in short and horizontal long-axis planes were acquired using TGrE (TR/TE/flip = 5.0/1.9/25) compared with SSFP (TR/TE/flip = 3.2/1.2/60). LV volumes and EF were measured with various geometric models for TGrE and SSFP. With three-dimensional data, the LV volumes were higher and the resulting EF lower for SSFP in contrast to TGrE (51 +/- 15% vs. 57 +/- 15%, p < 0.001). With SSFP, various geometric models yielded good to excellent correlations for LV volumes and LVEF compared to volumetric data (r = 0.94-0.98, mean relative difference 7.0-11.4%). In contrast, correlations were low using biplane or single-plane ellipsoid models in TGrE (r = 0.71-0.75, mean relative difference 15.9-30.2%). A new combined geometric model, taking all three dimensions into account, yielded the highest accuracy for SSFP in comparison to volumetric data (r = 0.99, mean relative difference 4.7%). Geometric models for assessment of LV volumes and EF yield higher accuracy and reproducibility by use of the SSFP sequence than by standard TGrE. This may increase clinical utility of magnetic resonance by shorter acquisition and processing times.

Performance of a new gadolinium-based intravascular contrast agent in free-breathing inversion-recovery 3D coronary MRA

In three‐dimensional (3D) coronary magnetic resonance angiography (MRA), the in‐flow contrast between the coronary blood and the surrounding myocardium is attenuated as compared to thin‐slab two‐dimensional (2D) techniques. The application of a gadolinium (Gd)‐based intravascular contrast agent may provide an additional source of signal and contrast by reducing T1blood and supporting the visualization of more distal or branching segments of the coronary arterial tree. In six healthy adults, the left coronary artery (LCA) system was imaged pre‐ and postcontrast with a 0.075‐mmol/kg bodyweight dose of the intravascular contrast agent B‐22956. For imaging, an optimized free‐breathing, navigator‐gated and ‐corrected 3D inversion recovery (IR) sequence was used. For comparison, state‐of‐the‐art baseline 3D coronary MRA with T2 preparation for non‐exogenous contrast enhancement was acquired. The combination of IR 3D coronary MRA, sophisticated navigator technology, and B‐22956 allowed for an extensive visualization of the LCA system. Postcontrast, a significant increase in both the signal‐to‐noise ratio (SNR; 46%, P < 0.05) and contrast‐to‐noise ratio (CNR; 160%, P < 0.01) was observed, while vessel sharpness of the left anterior descending (LAD) artery and the left coronary circumflex (LCX) were improved by 20% (P < 0.05) and 18% (P < 0.05), respectively. Magn Reson Med 49:115–121, 2003.

Visualization of the Cardiac Venous System Using Cardiac Magnetic Resonance

We sought to investigate the value of cardiac magnetic resonance to depict cardiac venous anatomy. For cardiac resynchronization therapy the lead for the left ventricle is usually placed by transvenous approach into a tributary of the coronary sinus (CS). Knowledge of the anatomy and variations of the cardiac venous system may facilitate the positioning of the left ventricle lead. The cardiac magnetic resonance examinations of 23 subjects (16 volunteers and 7 patients) were retrospectively analyzed. All examinations were performed using navigator-gated whole-heart steady-state free precession coronary artery imaging after administration of intravascular contrast agents (gadofosveset in volunteers; Gadomer-17 in patients). The cardiac venous system was visualized in all subjects. The most frequent anatomical variant observed (in 12 subjects [52%]) was a connection of the small cardiac vein to the CS at the crux cordis. In 10 subjects (44%) the small veins entered the right atrium independently from the CS, and the posterior interventricular vein was connected to the CS at the crux cordis. Only one subject had a disconnection between the CS and posterior interventricular vein, which entered into the right atrium independently. The mean distance of the posterior vein of the left ventricle and the left marginal vein to the ostium of the CS was 15.2+/-4.7 mm and 49.7+/-14.1 mm, respectively. In conclusion, the anatomy of the cardiac venous system and its anatomical variability can be described using cardiac magnetic resonance. Its preimplantation visualization may help to facilitate the implant procedure and to reduce fluoroscopy time.

Whole-heart dynamic three-dimensional magnetic resonance perfusion imaging for the detection of coronary artery disease defined by fractional flow reserve: determination of volumetric myocardial ischaemic burden and coronary lesion location

AIMS Dynamic three-dimensional-cardiac magnetic resonance (3D-CMR) perfusion proved highly diagnostic for the detection of angiographically defined coronary artery disease (CAD) and has been used to assess the efficacy of coronary stenting procedures. The present study aimed to relate significant coronary lesions as assessed by fractional flow reserve (FFR) to the volume of myocardial hypoenhancement on 3D-CMR adenosine stress perfusion imaging and to define the inter-study reproducibility of stress inducible 3D-CMR hypoperfusion. METHODS AND RESULTS A total of 120 patients with known or suspected CAD were examined in two CMR centres using 1.5 T systems. The protocol included cine imaging, 3D-CMR perfusion during adenosine infusion, and at rest followed by delayed enhancement (DE) imaging. Fractional flow reserve was recorded in epicardial coronary arteries and side branches with ≥2 mm luminal diameter and >40% severity stenosis (pathologic FFR < 0.75). Twenty-five patients underwent an identical repeat CMR examination for the determination of inter-study reproducibility of 3D-CMR perfusion deficits induced by adenosine. Three-dimensional CMR perfusion scans were visually classified as pathologic if one or more segments showed an inducible perfusion deficit in the absence of DE. Myocardial ischaemic burden (MIB) was measured by segmentation of the area of inducible hypoenhancement and normalized to left ventricular myocardial volume (MIB, %). Three-dimensional CMR perfusion resulted in a sensitivity, specificity, and diagnostic accuracy of 90, 82, and 87%, respectively. Substantial concordance was found for inter-study reproducibility [Lins correlation coefficient: 0.98 (95% confidence interval: 0.96-0.99)]. CONCLUSION Three-dimensional CMR stress perfusion provided high diagnostic accuracy for the detection of functionally significant CAD. Myocardial ischaemic burden measurements were highly reproducible and allowed the assessment of CAD severity.

Diagnostic Performance of Myocardial Perfusion MR at 3 T in Patients with Coronary Artery Disease

PURPOSE To prospectively determine the diagnostic performance of myocardial perfusion magnetic resonance (MR) imaging at 3 T for helping depict clinically relevant coronary artery stenosis (> or =50% diameter) in patients with suspected or known coronary artery disease (CAD), with coronary angiography as the reference standard. MATERIALS AND METHODS The study was approved by the local ethics committee; written informed consent was obtained. Vasodilator stress perfusion imaging by using a turbo field-echo sequence was obtained in 101 patients (71 men, 30 women; mean age, 62 years +/- 7.7 [standard deviation]) scheduled for coronary angiography. Myocardial ischemia was defined as stress-inducible perfusion deficit in arterial territories without delayed enhancement (DE) or additional stress-inducible perfusion deficit in territories with nontransmural DE. Images were evaluated in consensus by two blinded readers. Diagnostic performance was determined on per-patient and per-coronary artery territory bases. The number of dark rim artifacts in patients without DE was determined in a second read. Interobserver variability was assessed in 40 randomly selected patients. RESULTS One hundred one patients underwent MR examinations. Coronary angiography depicted relevant stenosis in 70 (69%) patients. Patient-based sensitivity and specificity were 90% and 71%, respectively. Sensitivity, specificity, and diagnostic accuracy for the detection of coronary stenosis in a specific territory were 76%, 89%, and 86%, respectively. In 24% of patients without DE, dark rim artifacts were detected, mostly in the left anterior descending artery territory (56%). In 40 randomly selected patients, there was agreement in the determination of myocardial perfusion deficits in 37 (93%, kappa = 0.79) patients. CONCLUSION Myocardial perfusion MR imaging by using saturation-recovery spoiled gradient-echo imaging at 3 T has an accuracy of 84% for depicting hemodynamically relevant coronary artery stenosis in patients with suspected and known CAD.