Head-to-head comparison of multiple cardiovascular magnetic resonance techniques for the detection and quantification of intramyocardial haemorrhage in patients with ST-elevation myocardial infarction.

OBJECTIVES: T2*-weighted (T2*w) is deemed as a reference standard for post-infarction intramyocardial haemorrhage (IMH). However, high proportion of T2* images is affected by off-resonance artefacts hampering image interpretation. Diagnostic accuracy and precision of alternative techniques for IMH diagnosis and quantification have been seldomly investigated. METHODS AND RESULTS: Between April 2016 and May 2017, 50 ST-segment elevation myocardial infarction patients (66% male, 57 ± 17 years) and 15 healthy controls (60% male, 58 ± 13) were consecutively enrolled. Subjects underwent head-to-head comparison of single mid-infarct slice acquired on black-blood T2-weighted short-TI-inversion recovery (T2w-STIR), bright-blood T2prep-steady-state-free precession (T2prep-SSFP), and T2/T1 maps for IMH diagnosis and quantification against T2*w. All images were graded for quality (grade 1: very poor; grade 4: excellent) and diagnostic confidence (Likert scale, 1: very unsure and 5: highly confident). Reduced relaxation time/hypointense region (hypocore) embedded in infarct-related oedema on T2 map, T1 map, and T2w-STIR had the best overall diagnostic accuracy (per-subject: 91%, 86%, and 86%, respectively; per segment: 95%, 93%, and 93%, respectively). By mixed-effects analysis, image quality, and diagnostic confidence were higher for T2 map and T1 maps than T2*w (p < 0.05 for both scores). For IMH quantification, hypocore on T2 map and T1 map strongly correlated (Spearman's r > 0.7, p < 0.001 for both) with IMH extent on T2*w and presented an overall excellent agreement on Bland-Altman analysis. By linear mixed model analysis, absolute hypocore size did not differ among T1-, T2 map, and T2*w. T2/T1 maps had the best intra- and inter-observer reproducibility among CMR techniques. CONCLUSION: Hypocore on T2/T1 map is the best alternative technique to T2*w for diagnosing and quantifying IMH in post-STEMI patients. KEY POINT: • Mapping techniques are the best alternatives for diagnosing post-infarction intramyocardial haemorrhage. • Mapping techniques are valuable tools for imaging intramyocardial haemorrhage.

Relationship between CMR-derived parameters of ischemia/reperfusion injury and the timing of CMR after reperfused ST-segment elevation myocardial infarction.

BACKGROUND: To investigate the influence of cardiovascular magnetic resonance (CMR) timing after reperfusion on CMR-derived parameters of ischemia/reperfusion (I/R) injury in patients with ST-segment elevation myocardial infarction (STEMI). METHODS: The study included 163 reperfused STEMI patients undergoing CMR during the index hospitalization. Patients were divided according to the time between revascularization and CMR (Trevasc-CMR: Tertile-1 ≤ 43; 43 < Tertile-2 ≤ 93; Tertile-3 > 93 h). T2-mapping derived area-at-risk (AAR) and intramyocardial-hemorrhage (IMH), and late gadolinium enhancement (LGE)-derived infarct size (IS) and microvascular obstruction (MVO) were quantified. T1-mapping was performed before and > 15 min after Gd-based contrast-agent administration yielding extracellular volume (ECV) of infarct. RESULTS: Main factors influencing I/R injury were homogenously balanced across Trevasc-CMR tertiles. T2 values of infarct and remote regions increased with increasing Trevasc-CMR tertiles (infarct: 60.0 ± 4.9 vs 63.5 ± 5.6 vs 64.8 ± 7.5 ms; P < 0.001; remote: 44.3 ± 2.8 vs 46.1 ± 2.8 vs ± 46.1 ± 3.0; P = 0.001). However, T2 value of infarct largely and significantly exceeded that of remote myocardium in each tertile yielding comparable T2-mapping-derived AAR extent throughout Trevasc-CMR tertiles (17 ± 9% vs 19 ± 9% vs 18 ± 8% of LV, respectively, P = 0.385). Similarly, T2-mapping-based IMH detection and quantification were independent of Trevasc-CMR. LGE-derived IS and MVO were not influenced by Trevasc-CMR (IS: 12 ± 9% vs 12 ± 9% vs 14 ± 9% of LV, respectively, P = 0.646). In 68 patients without MVO, T1-mapping based ECV of infarct region was comparable across Trevasc-CMR tertiles (P = 0.470). CONCLUSION: In STEMI patients, T2 values of infarct and remote myocardium increase with increasing CMR time after revascularization. However, these changes do not give rise to substantial variation of T2-mapping-derived AAR size nor of other CMR-based parameters of I/R. TRIAL REGISTRATION: ISRCTN03522116 . Registered 30.4.2018 (retrospectively registered).

[Myocardial fibrosis detected by cardiac MR : A substrate for ventricular arrhythmias and sudden cardiac death]. / Fibrose myocardique détectée à l'IRM cardiaque : un substrat aux arythmies ventriculaires et à la mort subite.

Myocardial fibrosis often develops in the setting of hypertrophic and dilated cardiomyopathies (CMP), but is also a common sequela after inflammatory CMP or following an acute myocardial infarction in patients with coronary artery disease. Cardiac magnetic resonance (CMR) provides a precise quantification of mass and spatial distribution of myocardial fibrosis by the so-called « late-gadolinium-enhancement ¼ (LGE) technique and current evidence is provided in this article linking fibrosis mass to outcome in these specific patient populations. The position of CMR fibrosis imaging in the current guidelines is discussed and suggestions are given how to integrate CMR fibrosis imaging in the work-up and risk stratification of these patient populations. Finally, a short outlook is given on anticipated developments on CMR fibrosis imaging and its integration into patient management.

La fibrose myocardique se développe fréquemment dans le contexte des cardiomyopathies hypertrophiques ou dilatatives, mais elle représente également une séquelle fréquente des cardiopathies inflammatoires ou de l'infarctus myocardique. L'IRM cardiaque permet la quantification précise de la masse fibrotique et de sa distribution spatiale par le « rehaussement tardif ¼. Cet article présente les données soutenant la relation entre la fibrose myocardique et le pronostic dans ces populations spécifiques. La place de l'imagerie de la fibrose par IRM dans les guidelines actuelles est discutée, de même que des suggestions d'intégration de la détection de fibrose par IRM cardiaque dans le bilan de ces patients. Enfin, les développements en cours dans le domaine de la fibrose en IRM sont brièvement évoqués, de même que leur potentielle intégration dans la prise en charge du patient.

Impact of bileaflet mitral valve prolapse on quantification of mitral regurgitation with cardiac magnetic resonance: a single-center study.

BACKGROUND: To quantify mitral regurgitation (MR) with CMR, the regurgitant volume can be calculated as the difference between the left ventricular (LV) stroke volume (SV) measured with the Simpson's method and the reference SV, i.e. the right ventricular SV (RVSV) in patients without tricuspid regurgitation. However, for patients with prominent mitral valve prolapse (MVP), the Simpson's method may underestimate the LV end-systolic volume (LVESV) as it only considers the volume located between the apex and the mitral annulus, and neglects the ventricular volume that is displaced into the left atrium but contained within the prolapsed mitral leaflets at end systole. This may lead to an underestimation of LVESV, and resulting an over-estimation of LVSV, and an over-estimation of mitral regurgitation. The aim of the present study was to assess the impact of prominent MVP on MR quantification by CMR. METHODS: In patients with MVP (and no more than trace tricuspid regurgitation) MR was quantified by calculating the regurgitant volume as the difference between LVSV and RVSV. LVSVuncorr was calculated conventionally as LV end-diastolic (LVEDV) minus LVESV. A corrected LVESVcorr was calculated as the LVESV plus the prolapsed volume, i.e. the volume between the mitral annulus and the prolapsing mitral leaflets. The 2 methods were compared with respect to the MR grading. MR grades were defined as absent or trace, mild (5-29% regurgitant fraction (RF)), moderate (30-49% RF), or severe (≥50% RF). RESULTS: In 35 patients (44.0 ± 23.0y, 14 males, 20 patients with MR) the prolapsed volume was 16.5 ± 8.7 ml. The 2 methods were concordant in only 12 (34%) patients, as the uncorrected method indicated a 1-grade higher MR severity in 23 (66%) patients. For the uncorrected/corrected method, the distribution of the MR grades as absent-trace (0 vs 11, respectively), mild (20 vs 18, respectively), moderate (11 vs 5, respectively), and severe (4 vs 1, respectively) was significantly different (p < 0.001). In the subgroup without MR, LVSVcorr was not significantly different from RVSV (difference: 2.5 ± 4.7 ml, p = 0.11 vs 0) while a systematic overestimation was observed with LVSVuncorr (difference: 16.9 ± 9.1 ml, p = 0.0007 vs 0). Also, RVSV was highly correlated with aortic forward flow (n = 24, R 2 = 0.97, p < 0.001). CONCLUSION: For patients with severe bileaflet prolapse, the correction of the LVSV for the prolapse volume is suggested as it modified the assessment of MR severity by one grade in a large portion of patients.

Stress Perfusion CMR in Patients With Known and Suspected CAD: Prognostic Value and Optimal Ischemic Threshold for Revascularization.

OBJECTIVES: This study sought to determine the ischemia threshold and additional prognostic factors that identify patients for safe deferral from revascularizations in a large cohort of all-comer patients with known or suspected coronary artery disease (CAD). BACKGROUND: Stress-perfusion cardiac magnetic resonance (CMR) is increasingly used in daily practice for ischemia detection. However, there is insufficient evidence about the ischemia burden that identifies patients who benefit from revascularization versus those with a good prognosis who receive drugs only. METHODS: All patients with known or suspected CAD referred to stress-perfusion CMR for myocardial ischemia assessment were prospectively enrolled. The CMR examination included standard functional adenosine stress first-pass perfusion (gadobutrol 0.1 mmol/kg Gadovist, Bayer AG, Zurich, Switzerland) and late gadolinium enhancement (LGE) acquisitions. Presence of ischemia and ischemia burden (number of ischemic segments on a 16-segment model), and of scar and scar burden (number and transmurality of scar segments in a 17-segment model) were assessed. The primary endpoint was a composite of cardiac death, nonfatal myocardial infarction (MI), and late coronary revascularization (>90 days post-CMR); the secondary endpoint was a composite of cardiac death and nonfatal MI. RESULTS: During a follow-up of 2.5 ± 1.0 years, 86 and 32 of 1,024 patients (1,103 screened patients) experienced the primary and secondary endpoints, respectively. On Kaplan-Meier curves for the primary and secondary endpoints, patients without ischemia had excellent outcomes that did not differ from patients with <1.5 ischemic segments. In multivariate Cox regression analyses of the entire population and of the subgroups, ischemia burden (threshold: ≥1.5 ischemic segments) was consistently the strongest predictor of the primary and secondary endpoints with hazard ratios (HRs) of 7.42 to 8.72 (p < 0.001), whereas age (≥67 years), left ventricular ejection fraction (≤40%), and scar burden (LGE score ≥0.03) contributed significantly, but to a lesser extent, in all models with HRs of 2.01 to 3.48, 1.75 to 1.96, and 1.66 to 1.76, respectively. CONCLUSIONS: In a large all-comer patient cohort with known and suspected CAD, an ischemia burden of ≥1.5 ischemic segments on stress-perfusion CMR was the strongest predictor of the primary and secondary endpoints. Patients with zero or 1 ischemic segment can be safely deferred from revascularizations.

Improved border sharpness of post-infarct scar by a novel self-navigated free-breathing high-resolution 3D whole-heart inversion recovery magnetic resonance approach.

The border zone of post-infarction myocardial scar as identified by late gadolinium enhancement (LGE) has been identified as a substrate for arrhythmias and consequently, high-resolution 3D scar information is potentially useful for planning of electrophysiological interventions. This study evaluates the performance of a novel high-resolution 3D self-navigated free-breathing inversion recovery magnetic resonance pulse sequence (3D-SN-LGE) vs. conventional 2D breath-hold LGE (2D-LGE) with regard to sharpness of borders (SBorder) of post-infarction scar. Patients with post-infarction scar underwent two magnetic resonance examinations for conventional 2D-LGE and high-resolution 3D-SN-LGE acquisitions (both 15 min after 0.2 mmol/kg Gadobutrol IV) at 1.5T. In the prototype 3D-SN-LGE sequence, each ECG-triggered radial steady-state-free-precession read-out segment is preceded by a non-slice-selective inversion pulse. Scar volume and SBorder were assessed on 2D-LGE and matching reconstructed high-resolution 3D-SN-LGE short-axis slices. In 16 patients (four females, 58 ± 10y) all scars visualized by 2D-LGE could be identified on 3D-SN-LGE (time between 2D-LGE and 3D-SN-LGE 48 ± 53 days). A good agreement of scar volume by 3D-SN-LGE vs. 2D-LGE was found (Bland-Altman: -3.7 ± 3.4 ml, correlation: r = 0.987, p < 0.001) with a small difference in scar volume (20.5 (15.8, 35.2) ml vs. 24.5 (20.0, 41.9)) ml, respectively, p = 0.002] and a good intra- and interobserver variability (1.1 ± 4.1 and -1.1 ± 11.9 ml, respectively). SBorder of border "scar to non-infarcted myocardium" was superior on 3D-SN-LGE vs. 2D-LGE: 0.180 ± 0.044 vs. 0.083 ± 0.038, p < 0.001. Detection and quantification of myocardial scar by 3D-SN-LGE is feasible and accurate in comparison to 2D-LGE. The high spatial resolution of the 3D sequence improves delineation of scar borders.

Single centre experience of the application of self navigated 3D whole heart cardiovascular magnetic resonance for the assessment of cardiac anatomy in congenital heart disease.

BACKGROUND: For free-breathing cardiovascular magnetic resonance (CMR), the self-navigation technique recently emerged, which is expected to deliver high-quality data with a high success rate. The purpose of this study was to test the hypothesis that self-navigated 3D-CMR enables the reliable assessment of cardiovascular anatomy in patients with congenital heart disease (CHD) and to define factors that affect image quality. METHODS: CHD patients ≥2 years-old and referred for CMR for initial assessment or for a follow-up study were included to undergo a free-breathing self-navigated 3D CMR at 1.5T. Performance criteria were: correct description of cardiac segmental anatomy, overall image quality, coronary artery visibility, and reproducibility of great vessels diameter measurements. Factors associated with insufficient image quality were identified using multivariate logistic regression. RESULTS: Self-navigated CMR was performed in 105 patients (55% male, 23 ± 12y). Correct segmental description was achieved in 93% and 96% for observer 1 and 2, respectively. Diagnostic quality was obtained in 90% of examinations, and it increased to 94% if contrast-enhanced. Left anterior descending, circumflex, and right coronary arteries were visualized in 93%, 87% and 98%, respectively. Younger age, higher heart rate, lower ejection fraction, and lack of contrast medium were independently associated with reduced image quality. However, a similar rate of diagnostic image quality was obtained in children and adults. CONCLUSION: In patients with CHD, self-navigated free-breathing CMR provides high-resolution 3D visualization of the heart and great vessels with excellent robustness.

Free-running 4D whole-heart self-navigated golden angle MRI: Initial results.

PURPOSE: To test the hypothesis that both coronary anatomy and ventricular function can be assessed simultaneously using a single four-dimensional (4D) acquisition. METHODS: A free-running 4D whole-heart self-navigated acquisition incorporating a golden angle radial trajectory was implemented and tested in vivo in nine healthy adult human subjects. Coronary magnetic resonance angiography (MRA) datasets with retrospective selection of acquisition window width and position were extracted and quantitatively compared with baseline self-navigated electrocardiography (ECG) -triggered coronary MRA. From the 4D datasets, the left-ventricular end-systolic, end-diastolic volumes (ESV & EDV) and ejection fraction (EF) were computed and compared with values obtained from conventional 2D cine images. RESULTS: The 4D datasets enabled dynamic assessment of the whole heart with isotropic spatial resolution of 1.15 mm(3). Coronary artery image quality was very similar to that of the ECG-triggered baseline scan despite some SNR penalty. A good agreement between 4D and 2D cine imaging was found for EDV, ESV, and EF. CONCLUSION: The hypothesis that both coronary anatomy and ventricular function can be assessed simultaneously in vivo has been tested positive. Retrospective and flexible acquisition window selection allows to best visualize each coronary segment at its individual time point of quiescence.

Compressed sensing single-breath-hold CMR for fast quantification of LV function, volumes, and mass.

OBJECTIVES: The purpose of this study was to compare a novel compressed sensing (CS)-based single-breath-hold multislice magnetic resonance cine technique with the standard multi-breath-hold technique for the assessment of left ventricular (LV) volumes and function. BACKGROUND: Cardiac magnetic resonance is generally accepted as the gold standard for LV volume and function assessment. LV function is 1 of the most important cardiac parameters for diagnosis and the monitoring of treatment effects. Recently, CS techniques have emerged as a means to accelerate data acquisition. METHODS: The prototype CS cine sequence acquires 3 long-axis and 4 short-axis cine loops in 1 single breath-hold (temporal/spatial resolution: 30 ms/1.5 × 1.5 mm(2); acceleration factor 11.0) to measure left ventricular ejection fraction (LVEF(CS)) as well as LV volumes and LV mass using LV model-based 4D software. For comparison, a conventional stack of multi-breath-hold cine images was acquired (temporal/spatial resolution 40 ms/1.2 × 1.6 mm(2)). As a reference for the left ventricular stroke volume (LVSV), aortic flow was measured by phase-contrast acquisition. RESULTS: In 94% of the 33 participants (12 volunteers: mean age 33 ± 7 years; 21 patients: mean age 63 ± 13 years with different LV pathologies), the image quality of the CS acquisitions was excellent. LVEF(CS) and LVEF(standard) were similar (48.5 ± 15.9% vs. 49.8 ± 15.8%; p = 0.11; r = 0.96; slope 0.97; p < 0.00001). Agreement of LVSV(CS) with aortic flow was superior to that of LVSV(standard) (overestimation vs. aortic flow: 5.6 ± 6.5 ml vs. 16.2 ± 11.7 ml, respectively; p = 0.012) with less variability (r = 0.91; p < 0.00001 for the CS technique vs. r = 0.71; p < 0.01 for the standard technique). The intraobserver and interobserver agreement for all CS parameters was good (slopes 0.93 to 1.06; r = 0.90 to 0.99). CONCLUSIONS: The results demonstrated the feasibility of applying the CS strategy to evaluate LV function and volumes with high accuracy in patients. The single-breath-hold CS strategy has the potential to replace the multi-breath-hold standard cardiac magnetic resonance technique.

Respiratory self-navigated postcontrast whole-heart coronary MR angiography: initial experience in patients.

PURPOSE: To assess the diagnostic performance of respiratory self-navigation for whole-heart coronary magnetic resonance (MR) angiography in a patient cohort referred for diagnostic cardiac MR imaging. MATERIALS AND METHODS: Written informed consent was obtained from all participants for this institutional review board-approved study. Self-navigated coronary MR angiography was performed after administration of a contrast agent in 78 patients (mean age, 48.5 years ± 20.7 [standard deviation]; 53 male patients) referred for cardiac MR imaging because of coronary artery disease (n = 40), cardiomyopathy (n = 14), congenital anomaly (n = 17), or "other" (n = 7). Examination duration was recorded, and the image quality for each coronary segment was assessed with consensus reading. Vessel sharpness, length, and diameter were measured. Quantitative values in proximal, middle, and distal segments were compared by using analysis of variance and t tests. A double-blinded comparison with the results of x-ray angiography was performed when such results were available. RESULTS: When patients with different indications for cardiac MR imaging were examined with self-navigated postcontrast coronary MR angiography, whole-heart data sets with 1.15-mm isotropic spatial resolution were acquired in an average of 7.38 minutes ± 1.85. The main and proximal coronary segments could be visualized in 92.3% of cases, while the middle and distal segments could be visualized in 84.0% and 55.8% of cases, respectively. Subjective scores and vessel sharpness were significantly higher in the proximal segments than in the middle and distal segments (P < .05). Anomalies of the coronary arteries could be confirmed or excluded in all cases. Per-vessel sensitivity and specificity for stenosis detection were 64.7% and 85.0%, respectively, in the 31 patients for whom reference standard x-ray coronary angiography results were available. CONCLUSION: The self-navigated coronary MR angiography sequence shows promise for coronary imaging. However, technical improvements are needed to improve image quality, especially in the more distal coronary segments.

Quality assessment of cardiovascular magnetic resonance in the setting of the European CMR registry: description and validation of standardized criteria.

BACKGROUND: Cardiovascular magnetic resonance (CMR) has become an important diagnostic imaging modality in cardiovascular medicine. However, insufficient image quality may compromise its diagnostic accuracy. We aimed to describe and validate standardized criteria to evaluate a) cine steady-state free precession (SSFP), b) late gadolinium enhancement (LGE), and c) stress first-pass perfusion images. These criteria will serve for quality assessment in the setting of the Euro-CMR registry. METHODS: Thirty-five qualitative criteria were defined (scores 0-3) with lower scores indicating better image quality. In addition, quantitative parameters were measured yielding 2 additional quality criteria, i.e. signal-to-noise ratio (SNR) of non-infarcted myocardium (as a measure of correct signal nulling of healthy myocardium) for LGE and % signal increase during contrast medium first-pass for perfusion images. These qualitative and quantitative criteria were assessed in a total of 90 patients (60 patients scanned at our own institution at 1.5T (n=30) and 3T (n=30) and in 30 patients randomly chosen from the Euro-CMR registry examined at 1.5T). Analyses were performed by 2 SCMR level-3 experts, 1 trained study nurse, and 1 trained medical student. RESULTS: The global quality score was 6.7±4.6 (n=90, mean of 4 observers, maximum possible score 64), range 6.4-6.9 (p=0.76 between observers). It ranged from 4.0-4.3 for 1.5T (p=0.96 between observers), from 5.9-6.9 for 3T (p=0.33 between observers), and from 8.6-10.3 for the Euro-CMR cases (p=0.40 between observers). The inter- (n=4) and intra-observer (n=2) agreement for the global quality score, i.e. the percentage of assignments to the same quality tertile ranged from 80% to 88% and from 90% to 98%, respectively. The agreement for the quantitative assessment for LGE images (scores 0-2 for SNR <2, 2-5, >5, respectively) ranged from 78-84% for the entire population, and 70-93% at 1.5T, 64-88% at 3T, and 72-90% for the Euro-CMR cases. The agreement for perfusion images (scores 0-2 for %SI increase >200%, 100%-200%,<100%, respectively) ranged from 81-91% for the entire population, and 76-100% at 1.5T, 67-96% at 3T, and 62-90% for the Euro-CMR registry cases. The intra-class correlation coefficient for the global quality score was 0.83. CONCLUSIONS: The described criteria for the assessment of CMR image quality are robust with a good inter- and intra-observer agreement. Further research is needed to define the impact of image quality on the diagnostic and prognostic yield of CMR studies.

Coronary vasomotor control in obesity and morbid obesity: contrasting flow responses with endocannabinoids, leptin, and inflammation.

OBJECTIVES: This study sought to investigate abnormalities in coronary circulatory function in 2 different disease entities of obese (OB) and morbidly obese (MOB) individuals and to evaluate whether these would differ in severity with different profiles of endocannabinoids, leptin, and C-reactive protein (CRP) plasma levels. BACKGROUND: There is increasing evidence that altered plasma levels of endocannabinoids, leptin, and CRP may affect coronary circulatory function in OB and MOB. METHODS: Myocardial blood flow (MBF) responses to cold pressor test from rest and during pharmacologically induced hyperemia were measured with N-13 ammonia positron emission tomography/computed tomography. Study participants (n = 111) were divided into 4 groups based on their body mass index (BMI) (kg/m(2)): 1) control group (BMI: 20 to 24.9, n = 30); 2) overweight group (BMI: 25 to 29.9, n = 31), 3) OB group (BMI: 30 to 39.9, n = 25); and 4) MOB group (BMI ≥40, n = 25). RESULTS: The cold pressor test-induced change in endothelium-related MBF response (ΔMBF) progressively declined in overweight and OB groups when compared with the control group [median: 0.19 (interquartile range [IQR] 0.08, 0.27) and 0.11 (0.03, 0.17) vs. 0.27 (0.23, 0.38) ml/g/min; p ≤ 0.01, respectively], whereas it did not differ significantly between OB and MOB groups [median: 0.11 (IQR: 0.03, 0.17) and 0.09 (-0.01, 0.19) ml/g/min; p = 0.93]. Compared with control subjects, hyperemic MBF subjects comparably declined in the overweight, OB, and MOB groups [median: 2.40 (IQR 1.92, 2.63) vs. 1.94 (1.65, 2.30), 2.05 (1.67, 2.38), and 2.14 (1.78, 2.76) ml/g/min; p ≤ 0.05, respectively]. In OB individuals, ΔMBF was inversely correlated with increase in endocannabinoid anandamide (r = -0.45, p = 0.044), but not with leptin (r = -0.02, p = 0.946) or with CRP (r = -0.33, p = 0.168). Conversely, there was a significant and positive correlation among ΔMBF and elevated leptin (r = 0.43, p = 0.031) and CRP (r = 0.55, p = 0.006), respectively, in MOB individuals that was not observed for endocannabinoid anandamide (r = 0.07, p = 0.740). CONCLUSIONS: Contrasting associations of altered coronary endothelial function with increases in endocannabinoid anandamide, leptin, and CRP plasma levels identify and characterize OB and MOB as different disease entities affecting coronary circulatory function.

Matching between regional coronary vasodilator capacity and corresponding circumferential strain in individuals with normal and increasing body weight.

BACKGROUND: To define the relationship between regional coronary vasodilator capacity and myocardial circumferential strain at rest in normal weight, overweight, and obese individuals with normal global left-ventricular function. METHODS AND RESULTS: Myocardial blood flow at rest and during pharmacologic vasodilation was measured with (13)N-ammonia PET/CT in mL/g/minute in normal weight control (CON, n = 12), overweight (OW, n = 10), and obese individuals (OB, n = 10). In addition, resting myocardial function was evaluated as circumferential strain (Єc, %) by MRI. Global myocardial flow reserve (MFR) did not differ significantly between CON and OW (2.98 ± 0.96 vs 2.70 ± 0.66, P = .290), whereas it declined significantly in OB (1.98 ± 1.04, P = .030). Further, global Єc (%) was comparable between CON, OW, and OB (-0.24 ± 0.03, -0.23 ± 0.02, and -0.23 ± 0.04) but it was lowest in OB when normalized to the rate-pressure product (NЄc: -0.31 ± 0.06, -0.32 ± 0.05, and -0.26 ± 0.08). When MFR of the three major coronary territories was correlated with corresponding Єc, a positive association was observed in CON (r = 0.36, P = .030), in OW (r = 0.54, P = .002), and also in OB when relating NЄc to coronary vascular resistance during pharmacologic vasodilation (r = -0.46, P = .010). CONCLUSIONS: Higher coronary vasodilator capacity is related to corresponding regional circumferential strain at rest in non-obese individuals, while this is also observed for reduced MFR in obesity.

Elevated endocannabinoid plasma levels are associated with coronary circulatory dysfunction in obesity.

AIMS: Aim of this study was to evaluate a possible association between endocannabinoid (EC) plasma levels, such as anandamide (AEA) and 2-arachidonoylglycerol (2-AG), and coronary circulatory function in obesity. METHODS AND RESULTS: Myocardial blood flow (MBF) responses to cold pressor test (CPT) and during pharmacological vasodilation with dipyridamole were measured with (13)N-ammonia PET/CT. Study participants (n = 77) were divided into three groups based on their body mass index (BMI, kg/m(2)): control group 20 ≤ BMI <25 (n = 21); overweight group, 25 ≤ BMI <30 (n = 26); and obese group, BMI ≥ 30 (n = 30). Anandamide plasma levels, but not 2-AG plasma levels, were significantly elevated in obesity as compared with controls, respectively [0.68 (0.53, 0.78) vs. 0.56 (0.47, 0.66) ng/mL, P = 0.020, and 2.2 (1.21, 4.59) vs. 2.0 (0.80, 5.90) ng/mL, P = 0.806)]. The endothelium-related change in MBF during CPT from rest (ΔMBF) progressively declined in overweight and obese when compared with control group [0.21 (0.10, 0.27) and 0.09 (-0.01, 0.15) vs. 0.26 (0.23, 0.39) mL/g/min; P = 0.010 and P = 0.0001, respectively). Compared with controls, hyperaemic MBFs were significantly lower in overweight and obese individuals [2.39 (1.97, 2.62) vs. 1.98 (1.69, 2.26) and 2.10 (1.76, 2.36); P = 0.007 and P = 0.042, respectively)]. In obese individuals, AEA and 2-AG plasma levels were inversely correlated with ΔMBF to CPT (r = -0.37, P = 0.046 and r = -0.48, P = 0.008) and hyperaemic MBFs (r = -0.38, P = 0.052 and r = -0.45, P = 0.017), respectively. CONCLUSIONS: Increased EC plasma levels of AEA and 2-AG are associated with coronary circulatory dysfunction in obese individuals. This observation might suggest increases in EC plasma levels as a novel endogenous cardiovascular risk factor in obesity, but needing further investigations.

Structural epicardial disease and microvascular function are determinants of an abnormal longitudinal myocardial blood flow difference in cardiovascular risk individuals as determined with PET/CT.

BACKGROUND: The aim of this study was to determine whether epicardial structural disease may affect the manifestation of a longitudinal decrease in myocardial blood flow (MBF) or MBF difference during hyperemia in cardiovascular risk individuals, and its dependency on the flow increase. METHODS AND RESULTS: In 54 cardiovascular risk individuals (at risk) and in 26 healthy controls, MBF was measured with (13)N-ammonia and PET/CT in mL/g/min at rest and during dipyridamole stimulation. Computed tomography coronary angiography (CTA) was performed using a 64-slice CT of a PET/CT system. Absolute MBFs during dipyridamole stimulation were mildly lower in the mid-distal than in the mid-LV myocardium in controls (2.20 ± .51 vs 2.29 ± .51, P < .0001), while it was more pronounced in at risk with normal and abnormal CTA (1.56 ± .42 vs 1.91 ± .46 and 1.18 ± .34 vs 1.51 ± .40 mL/g/min, respectively, P < .0001), resulting in a longitudinal MBF difference that was highest in at risk with normal CTA, intermediate in at risk abnormal CTA, and lowest in controls (.35 ± .16 and .22 ± .09 vs .09 ± .04 mL/g/min, respectively, P < .0001). On multivariate analysis, log-CCS and mid-LV hyperemic MBF increase, indicative of microvascular function, were independent predictors of the observed longitudinal MBF difference (P ≤ .004 by ANOVA). CONCLUSIONS: Epicardial structural disease and microvascular function are important determinants of an abnormal longitudinal MBF difference as determined with PET/CT.

Noninvasive stress testing of myocardial perfusion defects: head-to-head comparison of thallium-201 SPECT to MRI perfusion.

BACKGROUND: To evaluate the diagnostic value of magnetic resonance imaging (MRI) of myocardial perfusion in the assessment of flow-limiting epicardial stenosis in a head-to-head comparison with abnormal thallium-201 ((201)TI) single photon emission tomography (SPECT) studies in patients with predominantly known coronary artery disease (CAD). METHODS AND RESULTS: Twenty-one patients (mean age 65 +/- 10 years) with reversible myocardial perfusion defects on (201)TI-SPECT images during dipyridamole-stimulated hyperemia were recruited for study purpose. Within 5 days of the (201)TI-SPECT study, myocardial perfusion was studied again with MRI during dipyridamole stimulation and at rest. Overall, (201)TI-SPECT identified 30 reversible regional perfusion defects. The sensitivity to detect hypoperfused segments was 70% (21/30) with the GRE-MRI perfusion analysis with (201)TI-SPECT as reference. When patients were subgrouped according to the extent of regional reversible perfusion defects on (201)TI-SPECT, mild- (SDS: 2-4), moderate- (SDS: 5-8), and severe- (SDS > 8) perfusion defects were also identified by GRE-MRI perfusion analysis in 75% (6/8), in 56% (9/16) and 100% (6/6), respectively. CONCLUSIONS: GRE-MRI first-pass stress perfusion imaging may not identify up to 30% of mild-to-moderate perfusion defects in a group of preselected patients with predominantly known CAD and abnormal (201)TI-SPECT studies.

Effect of revascularizing viable myocardium on left ventricular diastolic function in patients with ischaemic cardiomyopathy.

AIMS: In patients with ischaemic left ventricular (LV) dysfunction and viable myocardium, revascularization improves systolic function. Diastolic dysfunction is also present in such patients; however, whether revascularization improves diastolic function also is largely unknown. METHODS: Twenty-six patients with chronic ischaemic cardiomyopathy [ejection fraction (EF) 32 +/- 6%, wall motion score index (WMSI) 2.45 +/- 0.33] and viable myocardium (low-dose dobutamine echocardiography) were examined at baseline and > or =4 months after revascularization. Diastolic function was assessed by transmitral pulsed-wave Doppler and tissue Doppler imaging (TDI) at the mitral annulus. RESULTS: At baseline, 62% of patients showed non-restrictive filling (non-RF) pattern, and 38% restrictive filling (RF) pattern. After revascularization, along with improvement in systolic function (EF 43 +/- 10%, WMSI 1.78 +/- 0.47, P = 0.0002 for both), diastolic filling improved in most patients, with only three patients still exhibiting RF pattern (P = 0.016); furthermore, E' velocity increased (32 +/- 42%, P = 0.0028) and E/E' decreased (-19 +/- 31%, P = 0.0378) compared with baseline. Left ventricular filling pressure also decreased, from 17.5 +/- 6.8 to 13.1 +/- 6.5 mmHg (P = 0.005). Improvement of diastolic function by TDI was related to the extent of viability at baseline (P = 0.0098) and to LV reverse remodelling after revascularization (P = 0.0092). CONCLUSION: In patients with ischaemic cardiomyopathy, LV diastolic filling may largely improve after revascularization. Improvement of diastolic dysfunction is related to the amount of viable tissue and it may represent an additional advantage of revascularizing dyssinergic but viable myocardium.

Diagnostic value of PET-measured heterogeneity in myocardial blood flows during cold pressor testing for the identification of coronary vasomotor dysfunction.

BACKGROUND: We aimed to evaluate the diagnostic value of a positron emission tomography (PET)-measured heterogeneity in longitudinal myocardial blood flow (MBF) during cold pressor testing (CPT) and global MBF response to CPT from rest (DeltaMBF) for identification of coronary vasomotor dysfunction. METHODS AND RESULTS: In 35 patients CPT-induced alterations in epicardial luminal area were determined with quantitative angiography as the reference. MBF was assessed over the whole left ventricle as global MBF and regionally in the mid and mid-distal myocardium as MBF difference or MBF heterogeneity with nitrogen-13 ammonia and PET. The sensitivity and specificity of a longitudinal MBF difference during CPT in the identification of epicardial vasomotor dysfunction were significantly higher than the global DeltaMBF to CPT (88% vs 79% and 82% vs 64%, respectively; P < .05). Combining both parameters resulted in an optimal sensitivity of 100% at the expense of an intermediate specificity of 73%. The diagnostic accuracy was higher for the combined analysis than that for the MBF difference alone and global DeltaMBF alone (91% vs 86% and 74%, respectively; P < .05). CONCLUSIONS: The combined evaluation of a CPT-induced heterogeneity in longitudinal MBF and the change in global MBF from rest may emerge as a new promising analytic approach to further optimize the identification and characterization of coronary vasomotor dysfunction.