Multimodality imaging approach in the diagnosis of chronic myocarditis with preserved left ventricular ejection fraction (MCpEF): The role of 2D speckle-tracking echocardiography.

BACKGROUND: Up to one third of patients with chronic myocarditis (MC) have preserved left ventricular (LV) ejection fraction (MCpEF). The purpose of this study was to evaluate the role of adding 2D speckle-tracking echocardiography (STE) to cardiac magnetic resonance imaging (cMRI) in the diagnosis of patients with MCpEF. METHODS AND RESULTS: We analyzed 67 patients with suspected MCpEF who underwent endomyocardial biopsy (EMB). Thirty-two patients with confirmed chronic myocardial inflammation by EMB served as study group (MCpEF) and the remaining patients (n=35) served as control group. In all patients, 2D STE and cMRI were performed within 48h before EMB. Patients with MCpEF had significantly lower LV global longitudinal systolic strain (GLS) than controls (GLS: -17.01±2.42% vs. -19.39±3.81%, p<0.001; respectively). In line, an abnormal GLS had adequate diagnostic performance to detect MCpEF (sensitivity, specificity, and accuracy of 82%, 70%, and 76%, respectively), which was superior to cMRI based on the Lake-Louise criteria (sensitivity, specificity, and accuracy 54%, 71%, and 67%, respectively). In addition, adding GLS to the Lake-Louise criteria improved significantly the diagnostic performance of cMRI to detect MCpEF (sensitivity, specificity, and accuracy 96%, 55%, and 75%, respectively). CONCLUSION: The findings of this study suggest that GLS using 2D STE could play an important role in the diagnostic evaluation of patients with suspected chronic myocarditis with preserved LV ejection fraction (MCpEF).

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.

AIMS: Perfusion-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. METHODS AND RESULTS: In 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. CONCLUSION: In 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.

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).

BACKGROUND: Perfusion-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. METHODS: In 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 4 weeks 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. RESULTS: The diagnostic performance (= area under ROC = AUC) of CMR was superior to SPECT (p = 0.0004, n = 425) and to gated-SPECT (p = 0.018, n = 253). CMR performed better than SPECT in MVD (p = 0.003 vs all SPECT, p = 0.04 vs gated-SPECT), in men (p = 0.004, n = 313) and in women (p = 0.03, n = 112) as well as in the non-infarct patients (p = 0.005, n = 186 in 1-3 vessel disease and p = 0.015, n = 140 in MVD). CONCLUSION: In 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 REGISTRATION: ClinicalTrials.gov, Identifier: NCT00977093.

Myocardial first-pass perfusion: influence of spatial resolution and heart rate on the dark rim artifact.

Myocardial perfusion images can be affected by the dark rim artifact. This study aimed to evaluate the effects of the spatial resolution and heart rate on the transmural extent of the artifact. Six pigs under anesthesia were scanned at 1.5T using an echo-planar imaging/fast gradient echo sequence with a nonselective saturation preparation pulse. Three short-axis slices were acquired every heart beat during the first pass of a contrast agent bolus. Two different in-plane spatial resolutions (2.65 and 3.75 mm) and two different heart rates (normal and tachycardia) were used, generating a set of four perfusion scans. The percentage drop of signal in the subendocardium compared to the epicardium and the transmural extent of the artifact were extracted. Additionally, the signal-to-noise and the contrast-to-noise ratios were evaluated. The signal drop as well as the width of the dark rim artifact increased with decreased spatial resolution and with increased heart rates. No significant slice-to-slice variability was detected for signal drop and width of the rim within the four considered groups. signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) ratios decreased with increasing spatial resolution. In conclusion, low spatial and temporal resolution could be correlated with increased extent of the dark-rim artifact and with lower SNR and CNR.

Development of diastolic heart failure in a 6-year follow-up study in patients after acute myocarditis.

BACKGROUND: The aim of this study was to analyse the long-term prognosis of patients with acute myocarditis (AMC) who had been discharged from hospital while having normal left ventricular (LV) function. METHODS AND RESULTS: 50 patients with acute myocarditis who underwent endomyocardial biopsies (EMBs) were prospectively studied. Their clinical condition was examined during a mean follow-up period of 72 (54-78) months, including tissue Doppler imaging (TDI). 4% (2/50) died, and 6% (3/50) developed dilated cardiomyopathy. 45/50 (90%) showed a normal or improvement in LV function over time. In the course of the follow-up, 49% (22/45) suffered from heart failure symptoms despite a normal ejection fraction (HFNEF). This was associated with an abnormal E/A ratio, an impaired deceleration time of early mitral flow velocity and isovolumic relaxation time, and a pathological increase in the LV filling index E/E', in contrast to patients without heart failure symptoms (E/E'(septal) 10.9 (9.3-13.8) vs 6.8 (6.4-9.1); p=0.001). Plasma N-terminal proB-type natriuretic peptide levels were increased threefold in patients with HFNEF (19.9 (10.6-24.1) vs 7.3 (4.2-11.9) pmol/l; p=0.006). CONCLUSIONS: It is assumed that the evidence for AMC is associated not only with the risk of developing LV dilatation but also with an increased risk of symptomatic diastolic dysfunction after several years.

MR-IMPACT: comparison of perfusion-cardiac magnetic resonance with single-photon emission computed tomography for the detection of coronary artery disease in a multicentre, multivendor, randomized trial.

AIMS: To determine in a multicentre, multivendor trial the diagnostic performance for perfusion-cardiac magnetic resonance (perfusion-CMR) in comparison with coronary X-ray angiography (CXA) and single-photon emission computed tomography (SPECT). METHODS AND RESULTS: Of 241 eligible patients from 18 centres, 234 were randomly dosed with 0.01, 0.025, 0.05, 0.075, or 0.1 mmol/kg Gd-DTPA-BMA (Omniscantrade mark, GE-Healthcare) per stress (0.42 mg/kg adenosine) and rest perfusion study. Coronary artery disease (CAD) was defined as diameter stenosis > or =50% on quantitative CXA. Five CMR and eight SPECT studies (of 225 complete studies) were excluded from analyses due to inadequate quality (three blinded readers scored per modality). The comparison of CMR vs. SPECT was based on receiver operating characteristic (ROC) analysis. Perfusion-CMR at the optimal CM dose (0.1 mmol/kg) had similar performance as SPECT, if only the SPECT studies of the 42 patients with this dose were considered [area under ROC curve (AUC): 0.86 +/- 0.06 vs. 0.75 +/- 0.09 for SPECT, P = 0.12]; however, diagnostic performance of perfusion-CMR was better vs. the entire SPECT population (AUC: 0.67 +/- 0.05, n = 212, P = 0.013). CONCLUSIONS: In this multicentre, multivendor trial, ROC analyses suggest perfusion-CMR as a valuable alternative to SPECT for CAD detection showing equal performance in the head-to-head comparison. Comparing perfusion-CMR with the entire SPECT population suggests CMR superiority over SPECT, which warrants further evaluation in larger trials.

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 beta-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-alpha, interleukin-6, and macrophage infiltration. Albuminuria was not reduced in BIRB796-treated dTGRs. Tubular and glomerular damage with tumor necrosis factor-alpha 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.

Elective percutaneous coronary intervention immediately impairs resting microvascular perfusion assessed by cardiac magnetic resonance imaging.

BACKGROUND: Percutaneous coronary intervention (PCI) is known to induce atherosclerotic plaque rupture, which may affect resting distal microvascular perfusion either through distal microvascular spasm or through embolization. We evaluated the effect of PCI on resting microvascular flow. METHODS: We performed cardiovascular magnetic resonance imaging to assess left ventricular systolic function and microvascular perfusion in 15 patients with stable coronary artery disease before and within 24 hours after PCI and in 10 control subjects without obstructive coronary artery disease on a clinical 1.5-T CMR scanner. Microvascular perfusion was evaluated at rest after injecting a bolus of gadolinium-diethylenetriamine pentaacetic acid (0.1 mmol/kg) by calculating the time to 50% maximum myocardial enhancement (T50% max), as well as the relative upslope, of the myocardial signal intensity curve. Regional perfusion and systolic thickening were evaluated using a 16-segment left ventricular model with the slice locations matched anatomically pre-PCI and post-PCI. The relative contrast delay in the region of myocardium subtended by the PCI artery was calculated by subtracting the T50% max of a remote region from the PCI region. RESULTS: In subjects with coronary artery disease, PCI resulted in a regional contrast delay (mean delay 0.6 +/- 0.2 seconds post-PCI vs 0.0 +/- 0.2 seconds pre-PCI, P < .05) and a reduction in the relative upslope (8.6 +/- 0.5 post-PCI vs 10.1 +/- 0.7 pre-PCI, P = .02), consistent with reduced microvascular perfusion. This was unaccompanied by any change in regional systolic thickening (54% +/- 7% pre-PCI vs 53% +/- 5% post-PCI, P = NS). CONCLUSIONS: The data show PCI-induced impairment of resting microvascular perfusion in the area of myocardium subtended by the treated artery after PCI, a likely consequence of iatrogenic atherosclerotic plaque rupture.

Cardiac hypertrophy in transgenic rats expressing a dominant-negative mutant of the natriuretic peptide receptor B.

Natriuretic peptides (NP) mediate their effects by activating membrane-bound guanylyl cyclase-coupled receptors A (NPR-A) or B (NPR-B). Whereas the pathophysiological role of NPR-A has been widely studied, only limited knowledge on the cardiovascular function of NPR-B is available. In vitro studies suggest antiproliferative and antihypertrophic actions of the NPR-B ligand C-type NP (CNP). Because of the lack of a specific pharmacological inhibitor, these effects could not clearly be attributed to impaired NPR-B signaling. Recently, gene deletion revealed a predominant role of NPR-B in endochondral ossification and development of female reproductive organs. However, morphological abnormalities and premature death of NPR-B-deficient mice preclude detailed cardiovascular phenotyping. In the present study, a dominant-negative mutant (NPR-BDeltaKC) was used to characterize CNP-dependent NPR-B signaling in vitro and in transgenic rats. Here we demonstrate that reduced CNP- but not atrial NP-dependent cGMP response attenuates antihypertrophic potency of CNP in vitro. In transgenic rats, NPR-BDeltaKC expression selectively reduced NPR-B but not NPR-A signaling. NPR-BDeltaKC transgenic rats display progressive, blood pressure-independent cardiac hypertrophy and elevated heart rate. The hypertrophic phenotype is further enhanced in chronic volume overload-induced congestive heart failure. Thus, this study provides evidence linking NPR-B signaling to the control of cardiac growth.

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.

Analysis of regional left ventricular function by cineventriculography, cardiac magnetic resonance imaging, and unenhanced and contrast-enhanced echocardiography: a multicenter comparison of methods.

OBJECTIVES: To define the use of cineventriculography, cardiac magnetic resonance imaging (cMRI), and unenhanced and contrast-enhanced echocardiography for detection of left ventricular (LV) regional wall motion abnormalities (RWMA). BACKGROUND: Detection of RWMA is integral to the evaluation of LV function. METHODS: In 100 patients, cineventriculography and unenhanced and contrast-enhanced echocardiography were performed. Fifty-six of the patients underwent additional cMRI. RWMA were assessed referring to a 16-segment model for cMRI, unenhanced and contrast echocardiography. Cineventriculography was evaluated on a 7-segment model. Hypokinesia in one or more segments defined presence of RWMA. Interobserver agreement among three readers was determined within each imaging modality. Intermethod agreement between imaging modalities was analyzed. A standard of truth for the presence of RWMA was obtained by an independent expert panel decision (EPD) based on clinical data, electrocardiogram, coronary angiography, and blinded information from the imaging modalities. RESULTS: Sixty-seven patients were found to have an RWMA by EPD. Interobserver agreement expressed as kappa coefficient was 0.41 (range 0.37 to 0.44) for unenhanced echocardiography, 0.43 (range 0.29 to 0.79) for cMRT, 0.56 (range 0.44 to 0.70) for cineventriculography, and 0.77 (range 0.71 to 0.88) for contrast echocardiography. Contrast enhancement compared to unenhanced echocardiography improved agreement of echocardiography related to cMRI (kappa 0.46 vs. 0.29) and related to cineventriculography (kappa 0.59 vs. 0.28). Accuracy to detect EPD-defined RWMA was highest for contrast echocardiography, followed by cMRI, unenhanced echocardiography, and cineventriculography. CONCLUSIONS: Analysis of RWMA is characterized by considerable interobserver variability even using high-quality imaging modalities. Interobserver agreement on RWMA and accuracy to detect panel-defined RWMA is good using contrast echocardiography.

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 week 7 (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.

Assessment of systolic left ventricular function: a multi-centre comparison of cineventriculography, cardiac magnetic resonance imaging, unenhanced and contrast-enhanced echocardiography.

AIMS: To assess the agreement of left ventricular ejection fraction (LVEF) determinations from unenhanced echocardiography, contrast-enhanced echocardiography, magnetic resonance imaging (MRI), and cineventriculography as well as the inter-observer agreement for each method. METHODS AND RESULTS: In 120 patients, with evenly distributed EF-groups (> 55, 35-55, < 35%), cineventriculography, unenhanced echocardiography with second harmonic imaging, and contrast echocardiography at low mechanical index with iv administration of SonoVue were performed. In addition, cardiac MRI at 1.5 T using a steady-state free precession sequence was performed in a subset of 55 patients. On-site, and two blinded off-site assessments were performed for unenhanced and contrast echocardiography, cineventriculography, and MRI according to pre-defined standards. Intra-class correlation coefficients (ICCs) were determined to assess inter-observer reliability between all three readers (i.e. one on-site and two off-site). EF was 56.2 +/- 18.3% by cineventriculography, 54.1 +/- 12.9% by MRI, 50.9 +/- 15.3% by unenhanced echocardiography, and 54.6 +/- 16.8% by contrast echocardiography. Correlation on EF between cineventriculography and echocardiography increased from 0.72 with unenhanced echocardiography to 0.83 with contrast echocardiography (P < 0.05). Similarly, correlation on EF between MRI and echocardiography increased from 0.60 with unenhanced echocardiography to 0.77 with contrast echocardiography (P < 0.05). The inter-observer reliability ICC was 0.91 (95% CI 0.88-0.94) in contrast echocardiography, followed by cardiac MRI (0.86; 95% CI 0.80-0.92), cineventriculography (0.80; 95% CI 0.74-0.85), and unenhanced echocardiography (0.79; 95% CI 0.74-0.85). CONCLUSIONS: Unenhanced echocardiography resulted in slight underestimation of EF and only moderate correlation compared with cineventriculography and MRI. Contrast echocardiography resulted in more accurate EF and significantly improved correlation with cineventriculography and MRI. Contrast echocardiography significantly improved inter-observer agreement on EF compared with unenhanced echocardiography. Inter-observer reliability on EF using contrast echocardiography reaches a level comparable to MRI and is better than those obtained by cineventriculography.

Cardiac gene expression profile in rats with terminal heart failure and cachexia.

About one-half of double transgenic rats (dTGR) overexpressing the human renin and angiotensinogen genes die by age 7 wk of terminal heart failure (THF); the other (preterminal) one-half develop cardiac damage but survive. Our study's aim was to elucidate cardiac gene expression differences in dTGR-THF compared with dTGR showing compensated cardiac hypertrophy but not yet THF. dTGR treated with losartan (LOS) and nontransgenic rats (SD) served as controls. THF-dTGR body weight was significantly lower than for all other groups. At death, THF-dTGR had blood pressures of 228 +/- 7 mmHg (cardiac hypertrophy index 6.2 +/- 0.1 mg/g). Tissue Doppler showed reduced peak early (Ea) to late (Aa) diastolic expansion in THF-dTGR, indicating diastolic function. Preterminal dTGR had blood pressures of 197 +/- 5 mmHg (cardiac hypertrophy index 5.1 +/- 0.1 mg/g); Ea < Aa compared with LOS-dTGR (141 +/- 6 mmHg; 3.7+/-0.1 mg/g; Ea > Aa) and SD (112 +/- 4 mmHg; 3.6 +/- 0.1 mg/g; Ea > Aa). Left ventricular RNA was isolated for the Affymetrix system and TaqMan RT-PCR. THF-dTGR and dTGR showed upregulation of hypertrophy markers and alpha/beta-myosin heavy chain switch to the fetal isoform. THF-dTGR (vs. dTGR) showed upregulation of 239 and downregulation of 150 genes. Various genes of mitochodrial respiratory chain and lipid catabolism were reduced. In addition, genes encoding transcription factors (CEBP-beta, c-fos, Fra-1), coagulation, remodeling/repair components (HSP70, HSP27, heme oxygenase), immune system (complement components, IL-6), and metabolic pathway were differentially expressed. In contrast, LOS-dTGR and SD had similar expression profiles. These data demonstrate that THF-dTGR show an altered expression profile compared with preterminal dTGR.

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 > or =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.

Dobutamine induced myocardial perfusion reserve index with cardiovascular MR in patients with coronary artery disease.

Currently, adenosine or dipyridamole is commonly used for the assessment of perfusion reserve. With intolerance to these agents, dobutamine can be used alternatively or it can be used for a combined examination of wall motion and perfusion. The aim of the study was to analyze the feasibility of cardiovascular magnetic resonance (CMR) to assess perfusion reserve with dobutamine. Alterations of myocardial perfusion were noninvasively assessed in 23 patients with and 4 without significant coronary artery disease by calculation of a myocardial perfusion reserve index from the upslope of the signal intensity curves of a first pass gadolinium bolus before and during dobutamine infusion (20 micrograms/min/kg). An ischemic threshold value of perfusion reserve index was determined from patients without significant coronary artery disease. Significant differences were found between ischemic and remote to ischemic segments in patients with single vessel disease (0.90 +/- 0.18 vs. 1.73 +/- 0.32, p < 0.0001). Differences between nonischemic segments in patients without and ischemic segments in patients with coronary artery disease were significant (2.0 +/- 0.39 vs. 0.97 +/- 0.20, p < 0.001). A cut-off value for myocardial perfusion reserve index of 1.22 for the detection of significant coronary artery stenosis yielded a sensitivity, specificity, and diagnostic accuracy of 81, 73, and 77%, respectively. Dobutamine MR is feasible in the evaluation of myocardial perfusion and can be used for the detection of myocardial ischemia alternatively to adenosine or dipyridamole in patients with coronary artery disease.