Nidal Al-Saadi

Noninvasive Detection of Myocardial Ischemia From Perfusion Reserve Based on Cardiovascular Magnetic Resonance

BACKGROUNDnMyocardial perfusion reserve can be noninvasively assessed with cardiovascular MR. In this study, the diagnostic accuracy of this technique for the detection of significant coronary artery stenosis was evaluated.nnnMETHODS AND RESULTSnIn 15 patients with single-vessel coronary artery disease and 5 patients without significant coronary artery disease, the signal intensity-time curves of the first pass of a gadolinium-DTPA bolus injected through a central vein catheter were evaluated before and after dipyridamole infusion to validate the technique. A linear fit was used to determine the upslope, and a cutoff value for the differentiation between the myocardium supplied by stenotic and nonstenotic coronary arteries was defined. The diagnostic accuracy was then examined prospectively in 34 patients with coronary artery disease and was compared with coronary angiography. A significant difference in myocardial perfusion reserve between ischemic and normal myocardial segments (1.08+/-0.23 and 2.33+/-0.41; P<0.001) was found that resulted in a cutoff value of 1.5 (mean minus 2 SD of normal segments). In the prospective analysis, sensitivity, specificity, and diagnostic accuracy for the detection of coronary artery stenosis (> or =75%) were 90%, 83%, and 87%, respectively. Interobserver and intraobserver variabilities for the linear fit were low (r=0.96 and 0.99).nnnCONCLUSIONSnMR first-pass perfusion measurements yielded a high diagnostic accuracy for the detection of coronary artery disease. Myocardial perfusion reserve can be easily and reproducibly determined by a linear fit of the upslope of the signal intensity-time curves.

MR-IMPACT II: Magnetic Resonance Imaging for Myocardial Perfusion Assessment in Coronary artery disease Trial: perfusion-cardiac magnetic resonance vs. single-photon emission computed tomography for the detection of coronary artery disease: a comparative multicentre, multivendor trial

AIMSnPerfusion-cardiac magnetic resonance (CMR) has emerged as a potential alternative to single-photon emission computed tomography (SPECT) to assess myocardial ischaemia non-invasively. The goal was to compare the diagnostic performance of perfusion-CMR and SPECT for the detection of coronary artery disease (CAD) using conventional X-ray coronary angiography (CXA) as the reference standard.nnnMETHODS AND RESULTSnIn this multivendor trial, 533 patients, eligible for CXA or SPECT, were enrolled in 33 centres (USA and Europe) with 515 patients receiving MR contrast medium. Single-photon emission computed tomography and CXA were performed within 4 weeks before or after CMR in all patients. The prevalence of CAD in the sample was 49%. Drop-out rates for CMR and SPECT were 5.6 and 3.7%, respectively (P = 0.21). The primary endpoint was non-inferiority of CMR vs. SPECT for both sensitivity and specificity for the detection of CAD. Readers were blinded vs. clinical data, CXA, and imaging results. As a secondary endpoint, the safety profile of the CMR examination was evaluated. For CMR and SPECT, the sensitivity scores were 0.67 and 0.59, respectively, with the lower confidence level for the difference of +0.02, indicating superiority of CMR over SPECT. The specificity scores for CMR and SPECT were 0.61 and 0.72, respectively (lower confidence level for the difference: -0.17), indicating inferiority of CMR vs. SPECT. No severe adverse events occurred in the 515 patients.nnnCONCLUSIONnIn this large multicentre, multivendor study, the sensitivity of perfusion-CMR to detect CAD was superior to SPECT, while its specificity was inferior to SPECT. Cardiac magnetic resonance is a safe alternative to SPECT to detect perfusion deficits in CAD.

Aldosterone Synthase Inhibitor Ameliorates Angiotensin II–Induced Organ Damage

Background—Aldosterone and angiotensin (Ang) II both may cause organ damage. Circulating aldosterone is produced in the adrenals; however, local cardiac synthesis has been reported. Aldosterone concentrations depend on the activity of aldosterone synthase (CYP11B2). We tested the hypothesis that reducing aldosterone by inhibiting CYP11B2 or by adrenalectomy (ADX) may ameliorate organ damage. Furthermore, we investigated how much local cardiac aldosterone originates from the adrenal gland. Methods and Results—We investigated the effect of the CYP11B2 inhibitor FAD286, losartan, and the consequences of ADX in transgenic rats overexpressing both the human renin and angiotensinogen genes (dTGR). dTGR-ADX received dexamethasone and 1% salt. Dexamethasone-treated dTGR-salt served as a control group in the ADX protocol. Untreated dTGR developed hypertension and cardiac and renal damage and had a 40% mortality rate (5/13) at 7 weeks. FAD286 reduced mortality to 10% (1/10) and ameliorated cardiac hypertrophy, albuminuria, cell infiltration, and matrix deposition in the heart and kidney. FAD286 had no effect on blood pressure at weeks 5 and 6 but slightly reduced blood pressure at week7 (177±6 mm Hg in dTGR+FAD286 and 200±5 mm Hg in dTGR). Losartan normalized blood pressure during the entire study. Circulating and cardiac aldosterone levels were reduced in FAD286 or losartan-treated dTGR. ADX combined with dexamethasone and salt treatment decreased circulating and cardiac aldosterone to barely detectable levels. At week 7, ADX-dTGR-dexamethasone-salt had a 22% mortality rate compared with 73% in dTGR-dexamethasone-salt. Both groups were similarly hypertensive (190±9 and 187±4 mm Hg). In contrast, cardiac hypertrophy index, albuminuria, cell infiltration, and matrix deposition were significantly reduced after ADX (P<0.05). Conclusions—Aldosterone plays a key role in the pathogenesis of Ang II–induced organ damage. Both FAD286 and ADX reduced circulating and cardiac aldosterone levels. The present results show that aldosterone produced in the adrenals is the main source of cardiac aldosterone.

Detection of Acutely Impaired Microvascular Reperfusion After Infarct Angioplasty With Magnetic Resonance Imaging

Background—Despite the reopening of the infarct-related artery (IRA) with infarct angioplasty, complete microvascular reperfusion does not always ensue. Methods and Results—We performed cardiovascular MRI (CMR) in 20 acute myocardial infarction (AMI) patients within 24 hours of successful infarct angioplasty and 10 control patients without obstructive coronary artery disease on a clinical 1.5-T CMR scanner. Three-month follow-up CMR in AMI patients evaluated the impact of abnormal reperfusion on recovery of function. Infarction was localized by delayed contrast hyperenhancement and impaired systolic thickening. Microvascular perfusion was assessed at rest by first-pass perfusion CMR after a bolus of gadolinium-DTPA by use of the time to 50% maximum myocardial enhancement. Whereas contrast wash-in was homogeneous in control patients, AMI patients exhibited delays in the hypokinetic region subtended by the IRA compared with remote segments in 19 of 20 patients, with a mean contrast delay of 0.9±0.1 seconds (95% CI, 0.6 to 1.2 seconds). At follow-up, the mean recovery of systolic thickening was lower in segments with a contrast delay of 2 seconds or more (10±7% versus 39±4%, P =0.001). A contrast delay ≥2 seconds and infarction >75% transmurally were independent predictors of impaired left ventricular systolic thickening at 3 months (P =0.002 for severe contrast delay, P =0.048 for >75% for transmural infarction). Conclusions—CMR detects impaired microvascular reperfusion in AMI patients despite successful infarct angioplasty, which when severe is associated with a lack of recovery of wall motion.

Apoptosis Repressor With Caspase Recruitment Domain Is Required for Cardioprotection in Response to Biomechanical and Ischemic Stress

Background— Ischemic heart disease and heart failure are associated with an increased loss of cardiomyocytes due to apoptosis. Whether cardiomyocyte apoptosis plays a causal role in the pathogenesis of heart failure remains enigmatic. The apoptosis repressor with caspase recruitment domain (ARC) is a recently discovered antiapoptotic factor with a highly specific expression pattern in striated muscle and neurons. ARC is a master regulator of cardiac death signaling because it is the only known factor that specifically inhibits both the intrinsic and extrinsic apoptotic death pathway. In this study we attempted to elucidate the physiological role of ARC and to understand pathophysiological consequences resulting from its deletion. Methods and Results— We generated ARC-deficient mice, which developed normally to adulthood and had no abnormality in cardiac morphology and function under resting conditions. On biomechanical stress induced by aortic banding, ARC-deficient mice developed accelerated cardiomyopathy compared with littermate controls, which was characterized by reduced contractile function, cardiac enlargement, and myocardial fibrosis. Likewise, ischemia/reperfusion injury of ARC-deficient mice resulted in markedly increased myocardial infarct sizes. Although in both instances a significant increase in apoptotic cardiomyocytes could be observed in ARC-deficient mice, neither in vitro nor in vivo studies revealed any effect of ARC on classic hypertrophic cardiomyocyte growth responses. The pathophysiological relevance of downregulated ARC levels was underscored by specimens from failing human hearts showing markedly reduced ARC protein levels. Conclusions— Our study identifies a tissue-specific antiapoptotic factor that is downregulated in human failing myocardium and that is required for cardioprotection in pressure overload and ischemia.

Superior diagnostic performance of perfusion-cardiovascular magnetic resonance versus SPECT to detect coronary artery disease: The secondary endpoints of the multicenter multivendor MR-IMPACT II (Magnetic Resonance Imaging for Myocardial Perfusion Assessment in Coronary Artery Disease Trial)

BackgroundPerfusion-cardiovascular magnetic resonance (CMR) is generally accepted as an alternative to SPECT to assess myocardial ischemia non-invasively. However its performance vs gated-SPECT and in sub-populations is not fully established. The goal was to compare in a multicenter setting the diagnostic performance of perfusion-CMR and gated-SPECT for the detection of CAD in various populations using conventional x-ray coronary angiography (CXA) as the standard of reference.MethodsIn 33 centers (in US and Europe) 533 patients, eligible for CXA or SPECT, were enrolled in this multivendor trial. SPECT and CXA were performed within 4u2009weeks before or after CMR in all patients. Prevalence of CAD in the sample was 49% and 515 patients received MR contrast medium. Drop-out rates for CMR and SPECT were 5.6% and 3.7%, respectively (ns). The study was powered for the primary endpoint of non-inferiority of CMR vs SPECT for both, sensitivity and specificity for the detection of CAD (using a single-threshold reading), the results for the primary endpoint were reported elsewhere. In this article secondary endpoints are presented, i.e. the diagnostic performance of CMR versus SPECT in subpopulations such as multi-vessel disease (MVD), in men, in women, and in patients without prior myocardial infarction (MI). For diagnostic performance assessment the area under the receiver-operator-characteristics-curve (AUC) was calculated. Readers were blinded versus clinical data, CXA, and imaging results.ResultsThe diagnostic performance (= area under ROCu2009=u2009AUC) of CMR was superior to SPECT (pu2009=u20090.0004, nu2009=u2009425) and to gated-SPECT (pu2009=u20090.018, nu2009=u2009253). CMR performed better than SPECT in MVD (pu2009=u20090.003 vs all SPECT, pu2009=u20090.04 vs gated-SPECT), in men (pu2009=u20090.004, nu2009=u2009313) and in women (pu2009=u20090.03, nu2009=u2009112) as well as in the non-infarct patients (pu2009=u20090.005, nu2009=u2009186 in 1–3 vessel disease and pu2009=u20090.015, nu2009=u2009140 in MVD).ConclusionIn this large multicenter, multivendor study the diagnostic performance of perfusion-CMR to detect CAD was superior to perfusion SPECT in the entire population and in sub-groups. Perfusion-CMR can be recommended as an alternative for SPECT imaging.Trial registrationClinicalTrials.gov, Identifier: NCT00977093

p38 Mitogen-Activated Protein Kinase Inhibition Ameliorates Angiotensin II–Induced Target Organ Damage

We investigated whether or not p38 mitogen-activated protein kinase inhibition ameliorates angiotensin II–induced target organ damage. We used double transgenic rats harboring both human renin and angiotensinogen genes (dTGRs). dTGR, with or without p38 inhibitor (BIRB796; 30 mg/kg per day in the diet), and nontransgenic Sprague–Dawley rats were studied in 2 protocols. In protocol 1 (week 7), systolic blood pressure of untreated dTGRs was 204±4 mm Hg, but partially reduced after BIRB796 treatment (166±7 mm Hg), whereas Sprague–Dawley rats were normotensive. The cardiac hypertrophy index was unchanged in untreated and BIRB796-treated dTGRs. The &bgr;-myosin heavy chain expression of BIRB796-treated hearts was significantly lower in BIRB796 compared with dTGRs, indicating a delayed switch to the fetal isoform. BIRB796 treatment significantly reduced cardiac fibrosis, connective tissue growth factor, tumor necrosis factor-&agr;, interleukin-6, and macrophage infiltration. Albuminuria was not reduced in BIRB796-treated dTGRs. Tubular and glomerular damage with tumor necrosis factor-&agr; expression was unaltered, although serum creatinine and cystatin C were normalized. Renal macrophage infiltration, fibrosis, and vessel damage were reduced. In protocol 2 (week 8), we focused on mortality and arrhythmogenic electrical remodeling. Mortality of untreated dTGRs was 100% but was reduced to 10% in the BIRB796 group. Cardiac magnetic field mapping showed prolongation of depolarization and repolarization in untreated dTGRs compared with Sprague–Dawley rats with a partial reduction by BIRB796. Programmed electrical stimulation elicited ventricular tachycardias in 81% of untreated dTGRs but only in 48% of BIRB796-treated dTGRs. In conclusion, BIRB796 improved survival, target organ damage, and arrhythmogenic potential in angiotensin II–induced target organ damage.

Towards automatic quantitative analysis of cardiac MR perfusion images

Magnetic Resonance Imaging (MRI) is a powerful technique for imaging cardiovascular diseases. The introduction of cardiovascular MRI into clinical practice is however hampered by the lack of efficient and reliable automatic image analysis methods. This paper focuses on the automatic evaluation of the perfusion of blood in the myocardium (the heart muscle) from cardiac MR perfusion image series, acquired using contrast-enhanced ECG-triggered MRI. We have developed a semi-automatic quantitative analysis method with which the perfusion image series can be analysed in only a few minutes. The method is described in this paper and preliminary validation results are presented.

Cardiovascular Magnetic Resonance

Cardiovascular Magnetic Resonance is an indispensable guide to performing and interpreting CMR scans. What to look for, which sequences to include, how to acquire them, and how to interpret the images are all included in the handbook. The information is provided in a quick-reference, easy-to-use format with many images from real cases, and is designed to sit on the scanning console or in the office, providing a step-by-step guide to aid the CMR practitioner at every stage. All areas of cardiovascular imaging are covered, including tips and tricks for optimal imaging and how to avoid and spot artefacts. From patient safety to differential diagnoses of tricky images, to an easy to understand section on the science behind magnetic resonance, all aspects are covered in this concise yet comprehensive guide to this specialist area. Whether a novice or expert in the field, all readers should find this book a useful tool. It is an invaluable reference that no CMR department should be without.Cardiovascular magnetic resonance (CMR) creates images from atomic nuclei with uneven spin using radio waves in the presence of a magnetic field. Full details of the physical principles can be found elsewhere [1]. For clinical purposes, MR is performed using hydrogen-1, which is abundant in water and fat. Radiofrequency waves excite the area of interest to create tissue magnetization, which decays (relaxation) and after a short period is induced to release energy as a radio signal. These echoes are converted using Fourier transformation into images of spatially resolved radio signals. Relaxation is quantified in spatially orthogonal directions as T1 and T2, which allows tissue characterization, thus creating a powerful clinical tool. A CMR scanner consists of a superconducting magnet, a radiofrequency transmitter and receiver connected to radio aerials, and gradient coils driven by powerful pulses of electricity to create transient magnetic fields. The imaging computer triggers to the electrocardiogram and runs scanning sequences that coordinate the complex processes.