Cost-Effectiveness of Cardiovascular Magnetic Resonance for Rejection Surveillance After Cardiac Transplantation in the Australian Health Care System.

BACKGROUND: Heart transplantation is an effective treatment for end-stage congestive heart failure, however, achieving the right balance of immunosuppression to maintain graft function while minimising adverse effects is challenging. Serial endomyocardial biopsies (EMBs) are currently the standard for rejection surveillance, despite being invasive. Replacing EMB-based surveillance with cardiac magnetic resonance (CMR)-based surveillance for acute cardiac allograft rejection has shown feasibility. This study aimed to assess the cost-effectiveness of CMR-based surveillance in the first year after heart transplantation. METHOD: A prospective clinical trial was conducted with 40 orthotopic heart transplant (OHT) recipients. Participants were randomly allocated into two surveillance groups: EMB-based, and CMR-based. The trial included economic evaluations, comparing the frequency and cost of surveillance modalities in relation to quality-adjusted life years (QALYs) within the first year post-transplantation. Sensitivity analysis encompassed modelled data from observed EMB and CMR arms, integrating two hypothetical models of expedited CMR-based surveillance. RESULTS: In the CMR cohort, 238 CMR scans and 15 EMBs were conducted, versus (vs) 235 EMBs in the EMB group. CMR surveillance yielded comparable rejection rates (CMR 74 vs EMB 94 events, p=0.10) and did not increase hospitalisation risk (CMR 32 vs EMB 46 events, p=0.031). It significantly reduced the necessity for invasive EMBs by 94%, lowered costs by an average of AUD$32,878.61, and enhanced cumulative QALY by 0.588 compared with EMB. Sensitivity analysis showed that increased surveillance with expedited CMR Models 1 and 2 were more cost-effective than EMB (all p<0.01), with CMR Model 1 achieving the greatest cost savings (AUD$34,091.12±AUD$23,271.86 less) and utility increase (+0.62±1.49 QALYs, p=0.011), signifying an optimal cost-utility ratio. Model 2 showed comparable utility to the base CMR model (p=0.900) while offering the benefit of heightened surveillance frequency during periods of elevated rejection risk. CONCLUSIONS: CMR-based rejection surveillance in orthotopic heart transplant recipients provides a cost-effective alternative to EMB-based surveillance. Furthermore, it reduces the need for invasive procedures, without increased risk of rejection or hospitalisation for patients, and can be incorporated economically for expedited surveillance. These findings have important implications for improving patient care and optimising resource allocation in post-transplant management.

Cardiovascular Magnetic Resonance for Rejection Surveillance After Cardiac Transplantation.

BACKGROUND: Endomyocardial biopsy (EMB) is the gold standard method for surveillance of acute cardiac allograft rejection (ACAR) despite its invasive nature. Cardiovascular magnetic resonance (CMR)-based myocardial tissue characterization allows detection of myocarditis. The feasibility of CMR-based surveillance for ACAR-induced myocarditis in the first year after heart transplantation is currently undescribed. METHODS: CMR-based multiparametric mapping was initially assessed in a prospective cross-sectional fashion to establish agreement between CMR- and EMB-based ACAR and to determine CMR cutoff values between rejection grades. A prospective randomized noninferiority pilot study was then undertaken in adult orthotopic heart transplant recipients who were randomized at 4 weeks after orthotopic heart transplantation to either CMR- or EMB-based rejection surveillance. Clinical end points were assessed at 52 weeks. RESULTS: Four hundred one CMR studies and 354 EMB procedures were performed in 106 participants. Forty heart transplant recipients were randomized. CMR-based multiparametric assessment was highly reproducible and reliable at detecting ACAR (area under the curve, 0.92; sensitivity, 93%; specificity, 92%; negative predictive value, 99%) with greater specificity and negative predictive value than either T1 or T2 parametric CMR mapping alone. High-grade rejection occurred in similar numbers of patients in each randomized group (CMR, n=7; EMB, n=8; P=0.74). Despite similarities in immunosuppression requirements, kidney function, and mortality between groups, the rates of hospitalization (9 of 20 [45%] versus 18 of 20 [90%]; odds ratio, 0.091; P=0.006) and infection (7 of 20 [35%] versus 14 of 20 [70%]; odds ratio, 0.192; P=0,019) were lower in the CMR group. On 15 occasions (6%), patients who were randomized to the CMR arm underwent EMB for clarification or logistic reasons, representing a 94% reduction in the requirement for EMB-based surveillance. CONCLUSIONS: A noninvasive CMR-based surveillance strategy for ACAR in the first year after orthotopic heart transplantation is feasible compared with EMB-based surveillance. REGISTRATION: HREC/13/SVH/66 and HREC/17/SVH/80. AUSTRALIAN NEW ZEALAND CLINICAL TRIALS REGISTRY: ACTRN12618000672257.

Defining the mid-diastolic imaging period for cardiac CT - lessons from tissue Doppler echocardiography.

BACKGROUND: Aggressive dose reduction strategies for cardiac CT require the prospective selection of limited cardiac phases. At lower heart rates, the period of mid-diastole is typically selected for image acquisition. We aimed to identify the effect of heart rate on the optimal CT acquisition phase within the period of mid-diastole. METHODS: We utilized high temporal resolution tissue Doppler to precisely measure coronary motion within diastole. Tissue-Doppler waveforms of the myocardium corresponding to the location of the circumflex artery (100 patients) and mid-right coronary arteries (50 patients) and the duration and timing of coronary motion were measured. Using regression analysis an equation was derived for the timing of the period of minimal coronary motion within the RR interval. In a validation set of 50 clinical cardiac CT examinations, we assessed coronary motion artifact and the effect of using a mid-diastolic imaging target that was adjusted according to heart rate vs a fixed 75% phase target. RESULTS: Tissue Doppler analysis shows the period of minimal cardiac motion suitable for CT imaging decreases almost linearly as the RR interval decreases, becoming extinguished at an average heart rate of 91 bpm for the circumflex (LCX) and 78 bpm for the right coronary artery (RCA). The optimal imaging phase has a strong linear relationship with RR duration (R2 = 0.92 LCX, 0.89 RCA). The optimal phase predicted by regression analysis of the tissue-Doppler waveforms increases from 74% at a heart rate of 55 bpm to 77% at 75 bpm. In the clinical CT validation set, the optimal CT acquisition phase similarly occurred later with increasing heart rate. When the selected cardiac phase was adjusted according to heart rate the result was closer to the optimal phase than using a fixed 75% phase. While this effect was statistically significant (p < 0.01 RCA/LCx), the mean effect of heart-rate adjustment was minor relative to typical beat-to-beat variability and available precision of clinical phase selection. CONCLUSION: High temporal resolution imaging of coronary motion can be used to predict the optimal acquisition phase in cardiac CT. The optimal phase for cardiac CT imaging within mid-diastole increases with increasing heart rate although the magnitude of change is small.

Accuracy and clinical outcomes of computed tomography coronary angiography in the presence of a high coronary calcium score.

BACKGROUND: A high coronary calcium burden may adversely affect image quality of CT coronary angiography (CTCA). The ability to rule out clinically significant disease in this setting is uncertain. METHODS: We examined CTCA findings in patients with a calcium score of >600. Utilising a search of death notices, structured patient interview and medical records, downstream investigations, cardiovascular events, revascularisation and mortality were recorded. RESULTS: Sixty patients with a calcium score >600 had CTCA performed on the same day. Coronary disease findings were: mild 28%, moderate 33%, severe 32% and non-diagnostic 7%. During a median 1.75-year follow-up, 31 (53%) of patients underwent further assessment for coronary disease, eight patients (13%) underwent revascularisation and there were two non-cardiovascular and one cardiovascular deaths. No patient with mild or moderate disease at CTCA had subsequently demonstrated ischaemia, was deemed to require PCI or suffered cardiac mortality. The negative predictive value of CTCA for subsequent PCI and all-cause mortality was 97% (100% for cardiac mortality only). The positive predictive value of CTCA for revascularisation or CV death was 42%. CONCLUSION: In patients with an elevated coronary calcium score, a negative CTCA implies an excellent short-term outcome and appears to exclude clinically significant coronary disease.

Grade 3 ischemia on the admission electrocardiogram is associated with severe microvascular injury on cardiac magnetic resonance imaging after ST elevation myocardial infarction.

BACKGROUND: Grade 3 ischemia during ST elevation myocardial infarction (STEMI) is defined as ST elevation with distortion of the terminal portion of the QRS on electrocardiogram (ECG). The aim of this study was to evaluate the effect of ischemic grade on cardiac magnetic resonance (CMR) imaging infarct characteristics such as infarct size, microvascular obstruction (MVO), intramyocardial hemorrhage (IMH), and myocardial salvage. METHODS: Patients with STEMI treated with primary percutaneous coronary intervention had a 12-lead ECG on presentation for analysis of ischemic grade. Gadolinium-enhanced CMR imaging was performed within 7 days to assess infarct size, MVO, IMH, and myocardial salvage. RESULTS: Of the 37 patients enrolled in the study, grade 3 ischemia was present in 32%. Those with grade 3 ischemia had higher peak troponin I levels (P = .013), more MVO (P < .001), more IMH (P < .001), larger infarct size (P = .025), and less myocardial salvage (P = .012). Regression analysis found that grade 3 ischemia, infarct size, and peak troponin I level were significantly associated with MVO and IMH. CONCLUSION: Grade 3 ischemia on the admission ECG during STEMI is closely associated with the development of severe microvascular damage on CMR imaging.

Dynamic Changes in ST Segment Resolution After Myocardial Infarction and the Association with Microvascular Injury on Cardiac Magnetic Resonance Imaging.

BACKGROUND: persistent ST elevation after reperfused ST elevation myocardial infarction (STEMI) is believed to be related to poor microvascular perfusion. Cardiac magnetic resonance imaging (CMR) can evaluate microvascular obstruction (MVO) and intramyocardial haemorrhage (IMH) both of which represent severe microvascular damage, have independent prognostic value and are dynamic and evolving over the first 48hours after reperfusion. The aim of this study was to assess whether the development of MVO or IMH has an impact upon ST segment resolution. METHODS: patients undergoing primary percutaneous coronary intervention (PCI) for STEMI had serial 12 lead electrocardiograms (ECG) from one hour after PCI until discharge. Persistent single lead maximal residual ST elevation (maxSTE) at each time point was calculated. ST segment deterioration (re-elevation) was calculated on each ECG until discharge compared with one hour post PCI ECG. CMR was performed within seven days post infarct utilising T2 weighted imaging to evaluate culprit artery area at risk (AAR) and IMH. Gadolinium delayed enhancement CMR quantified infarct size and MVO. RESULTS: in the 41 patients studied 58% had MVO and 41% had IMH. ST segment deterioration was more common in those with MVO or IMH (p=0.03 and p=0.008 respectively). MaxSTE was higher at each time point after PCI in those with MVO but only became statistically significant after 24hours. The measurement of maxSTE at 48 or 72hours after revascularisation provided the best correlation with the combination of infarct size, AAR, MVO and intramyocardial haemorrhage. CONCLUSION: microvascular injury as defined on CMR is associated with dynamic changes and persistence of ST segment elevation in the first 72hours after reperfusion.

Reproducibility of adenosine stress cardiovascular magnetic resonance in multi-vessel symptomatic coronary artery disease.

PURPOSE: First-pass perfusion cardiovascular magnetic resonance (CMR) is increasingly being utilized in both clinical practice and research. However, the reproducibility of this technique remains incompletely evaluated, particularly in patients with severe coronary artery disease (CAD). The purpose of this study was to determine the inter-study reproducibility of adenosine stress CMR in patients with symptomatic multi-vessel CAD and those at low risk for CAD. METHODS: Twenty patients (10 with CAD, 10 low risk CAD) underwent two CMR scans 8 +/- 2 days apart. Basal, mid and apical left ventricular short axis slices were acquired using gadolinium 0.05 mmol/kg at peak stress (adenosine, 140 micro/kg/min, 4 min) and rest. Myocardial perfusion was evaluated qualitatively by assessing the number of ischemic segments, and semi-quantitatively by determining the myocardial perfusion reserve index (MPRi) using a normalized upslope method. Inter-study and observer reproducibility were assessed--the latter being defined by the coefficient of variation (CoV), which was calculated from the standard deviation of the differences of the measurements, divided by the mean. Additionally, the percentage of myocardial segments with perfect agreement and inter- and intra-observer MPRi correlation between studies, were also determined. RESULTS: The CoV for the number of ischemic segments was 31% with a mean difference of -0.15 +/- 0.88 segments and 91% perfect agreement between studies. MPRi was lower in patients with CAD (1.13 +/- 0.21) compared to those with low risk CAD (1.59 +/- 0.58), p = 0.02. The reproducibility of MPRi was 19% with no significant difference between patients with CAD and those with low risk CAD (p = 0.850). Observer reproducibility for MPRi was high: inter-observer CoV 9%, r = 0.93 and intra-observer CoV 5%, r = 0.94. For trials using perfusion CMR as an endpoint, an estimated sample size of 12 subjects would be required to detect a two-segment change in the number of ischemic segments (power 0.9, alpha 0.05). CONCLUSIONS: Adenosine stress CMR, by qualitative and semi-quantitative normalized upslope analyses are reproducible techniques in both patients with multi-vessel CAD and those without known CAD. The robust inter-study reproducibility of perfusion CMR supports its clinical and research application.

Native T1 Mapping in the Diagnosis of Cardiac Allograft Rejection: A Prospective Histologically Validated Study.

OBJECTIVES: This study aimed to determine the role of T1 mapping in identifying cardiac allograft rejection. BACKGROUND: Endomyocardial biopsy (EMBx), the current gold standard to diagnose cardiac allograft rejection, is associated with potentially serious complications. Cardiac magnetic resonance (CMR)-based T1 mapping detects interstitial edema and fibrosis, which are important markers of acute and chronic rejection. Therefore, T1 mapping can potentially diagnose cardiac allograft rejection noninvasively. METHODS: Patients underwent CMR within 24 h of EMBx. T1 maps were acquired at 1.5-T. EMBx-determined rejection was graded according to International Society of Heart and Lung Transplant (ISHLT) criteria. RESULTS: Of 112 biopsies with simultaneous CMR, 60 were classified as group 0 (ISHLT grade 0), 35 as group 1 (ISHLT grade 1R), and 17 as group 2 (2R, 3R, clinically diagnosed rejection, antibody-mediated rejection). Native T1 values in patients with grade 0 biopsies and left ventricular ejection fraction >60% (983 ± 42 ms; 95% confidence interval: 972 to 994 ms) were comparable to values in nontransplant healthy control subjects (974 ± 45 ms; 95% confidence interval: 962 to 987 ms). T1 values were significantly higher in group 2 (1,066 ± 78 ms) versus group 0 (984 ± 42 ms; p = 0.0001) and versus group 1 (1,001 ± 54 ms; p = 0.001). After excluding patients with an estimated glomerular filtration rate <50 ml/min/m2, there was a moderate correlation of log-transformed native T1 with high-sensitivity troponin T (r = 0.54, p < 0.0001) and pro-B-type natriuretic peptide (r = 0.67, p < 0.0001). Using a T1 cutoff value of 1,029 ms, the sensitivity, specificity, and negative predictive value were 93%, 79%, and 99%, respectively. CONCLUSIONS: Myocardial tissue characterization with T1 mapping displays excellent negative predictive capacity for the noninvasive detection of cardiac allograft rejection and holds promise to reduce substantially the EMBx requirement in cardiac transplant rejection surveillance.

Comparative evaluation of long-term clinical efficacy with catheter-based percutaneous intramyocardial autologous bone marrow cell implantation versus laser myocardial revascularization in patients with severe coronary artery disease.

BACKGROUND: Catheter-based percutaneous laser myocardial revascularization (PMR) and intramyocardial direct bone marrow (BM) cell implantation have been investigated to treat patients with severe coronary artery disease (CAD). In both therapeutic approaches, direct local myocardial injury might be a common mechanism to induce therapeutic angiogenesis. METHODS: We studied the long-term clinical outcome in 16 patients with severe CAD who received either catheter-based PMR (n = 8) or intramyocardial autologous BM cell implantation (n = 8) as guided by electromechanical mapping. RESULTS: There were no significant differences in the baseline characteristics and the number of injection versus the number of laser pulse delivered between the 2 groups (P > .05). As compared with baseline, the New York Heart Association functional class and the number of anginal episodes were significantly reduced at 3- and 6-month follow-up in both BM and PMR groups (P < .05). However, the improvement in the New York Heart Association class and the reduction in anginal episodes at 18 months were only persisted in the BM group (P < .05) but not in the PMR group (P > .05). Furthermore, there were significant improvements in exercise time at 6- and 18-month follow-up, and the extent of stress-induced perfusion single-photon emission computed tomography defects at 6-month follow-up in BM group, as compared with baseline (all P < .05), but not in the PMR group (all P > .05). As compared with baseline, there were no significant changes in the total quality of life scores during follow-up in both groups (all P > .05). CONCLUSIONS: The results of this study demonstrated that the catheter-based intramyocardial autologous BM cell implantation might be more effective than PMR in improving symptoms and exercise capacity in patients with severe CAD. The beneficial effect of direct intramyocardial injection was over and beyond those noted in patients treated with PMR, suggesting a potential direct therapeutic effect of BM cells, rather than local myocardial injury alone on chronic ischemic myocardium.

Safety of catheter-based intramyocardial autologous bone marrow cells implantation for therapeutic angiogenesis.

The long-term safety and efficacy of autologous bone marrow cell implantation into the myocardium remains undefined. We studied the long-term clinical outcome of 12 patients with severe coronary artery disease who underwent electromechanical mapping-guided catheter-based autologous bone marrow cell implantation. Magnetic resonance imaging at 3 and 6 months showed no evidence of intramyocardial tumor formation, myocardial damage, or worsening of left ventricular ejection fraction. No sustained arrhythmia was detected on 24-hour Holter monitoring. After 44 +/- 10 months of follow-up, 1 patient had died of stroke at 8 months and another patient had died of myocardial infarction at 20 months. Computed tomography at 36 months or postmortem examination showed no tumor formation or intramyocardial calcification at the treated sites, and no sustained ventricular arrhythmia or sudden death was observed. Autologous bone marrow cell implantation into the ischemic human myocardium was not associated with long-term major adverse events regarding tumor, scar, or calcification formation, and the arrhythmogenic risk was low.

Impact of scar thickness on the assessment of viability using dobutamine echocardiography and thallium single-photon emission computed tomography: a comparison with contrast-enhanced magnetic resonance imaging.

OBJECTIVES: We sought to determine whether the transmural extent of scar (TES) explains discordances between dobutamine echocardiography (DbE) and thallium single-photon emission computed tomography (Tl-SPECT) in the detection of viable myocardium (VM). BACKGROUND: Discrepancies between DbE and Tl-SPECT are often attributed to differences between contractile reserve and membrane integrity, but may also reflect a disproportionate influence of nontransmural scar on thickening at DbE. METHODS: Sixty patients (age 62 +/- 12 years; 10 women and 50 men) with postinfarction left ventricular dysfunction underwent standard rest-late redistribution Tl-SPECT and DbE. Viable myocardium was identified when dysfunctional segments showed Tl activity >60% on the late-redistribution image or by low-dose augmentation at DbE. Contrast-enhanced magnetic resonance imaging (ceMRI) was used to divide TES into five groups: 0%, <25%, 26% to 50%, 51% to 75%, and >75% of the wall thickness replaced by scar. RESULTS: As TES increased, both the mean Tl uptake and change in wall motion score decreased significantly (both p < 0.001). However, the presence of subendocardial scar was insufficient to prevent thickening; >50% of segments still showed contractile function with TES of 25% to 75%, although residual function was uncommon with TES >75%. The relationship of both tests to increasing TES was similar, but Tl-SPECT identified VM more frequently than DbE in all groups. Among segments without scar or with small amounts of scar (<25% TES), >50% were viable by SPECT. CONCLUSIONS: Both contractile reserve and perfusion are sensitive to the extent of scar. However, contractile reserve may be impaired in the face of no or minor scar, and thickening may still occur with extensive scar.

Toward clinical risk assessment in hypertrophic cardiomyopathy with gadolinium cardiovascular magnetic resonance.

OBJECTIVES: We sought to assess whether hyperenhancement by gadolinium cardiovascular magnetic resonance (CMR) occurs in hypertrophic cardiomyopathy (HCM) and correlates with the risk of heart failure and sudden death. BACKGROUND: The myocardial interstitium is abnormal in HCM at post-mortem. Focally increased interstitial myocardial space appears as hyperenhancement with gadolinium CMR. METHODS: In a blinded, prospective study, HCM patients were selected for the presence (n = 23) or absence (n = 30) of an increased clinical risk of sudden death and/or progressive adverse left ventricular (LV) remodeling. Gadolinium-enhanced CMR was performed. RESULTS: Myocardial hyperenhancement was found in 42 patients (79%), affecting 10.9% (range 0% to 48%) of the LV mass. There was a greater extent of hyperenhancement in patients with progressive disease (28.5% vs. 8.7%, p < 0.001) and in patients with two or more risk factors for sudden death (15.7% vs. 8.6%, p = 0.02). Improved discrimination was seen in patients >40 years old (29.6% vs. 6.7%, p < 0.001) for progressive disease and for patients <40 years old for risk factors for sudden death (15.7% vs. 2.1%, p = 0.002). Patients with diffuse rather than confluent enhancement had two or more risk factors for sudden death (87% vs. 33%, p = 0.01). CONCLUSIONS: Gadolinium CMR reveals myocardial hyperenhancement in HCM. The extent of hyperenhancement is associated with progressive ventricular dilation and markers of sudden death.

Androgens up-regulate atherosclerosis-related genes in macrophages from males but not females: molecular insights into gender differences in atherosclerosis.

OBJECTIVES: This study investigated the effects of androgens on gene expression in male- and female-donor macrophages. BACKGROUND: Men have more severe coronary disease than women. Androgen exposure increases foam cell formation in male but not female macrophages, and male macrophages express >4-fold more androgen receptor messenger ribonucleic acid than female macrophages. Therefore, androgen exposure may have gender-specific and potentially pro-atherogenic effects in macrophages. METHODS: Utilizing complementary deoxyribonucleic acid arrays, we studied the effects of a pure androgen (dihydrotestosterone, 40 nmol/l) on human monocyte-derived macrophages from healthy male and female donors (n = 4 hybridizations; 2 men, 2 women). Differential expression of atherosclerosis-related genes was confirmed by real-time reverse transcription-polymerase chain reaction (RT-PCR) in five male and five female donors. Functional corroboration of foam cell formation-related findings was undertaken by experiments using (125)I-acetylated low-density lipoprotein (AcLDL). RESULTS: In male macrophages, androgen treatment produced differential up-regulation of 27 genes concentrated in five functional classes: 1) lipoprotein processing; 2) cell-surface adhesion; 3) extracellular signaling; 4) coagulation and fibrinolysis; and 5) transport protein genes. By contrast, none of 588 genes were up-regulated in female macrophages. By RT-PCR, we confirmed the gender-specific up-regulation of six of these atherosclerosis-related genes: acyl coenzyme A:cholesterol acyl transferase I, lysosomal acid lipase (LAL), caveolin-2, CD40, vascular endothelial growth factor-165 receptor, and tissue factor pathway inhibitor. Functionally, androgen-treated male macrophages showed increased rates of lysosomal AcLDL degradation, by 45% to 75% after 15 to 20 h of (125)I-AcLDL incubation (p = 0.001), consistent with increased LAL activity. CONCLUSIONS: Androgens increase expression of atherosclerosis-related genes in male but not female macrophages, with functional consequences. These findings may contribute to the male predisposition to atherosclerosis.

Native T1 in discrimination of acute and convalescent stages in patients with clinical diagnosis of myocarditis: a proposed diagnostic algorithm using CMR.

OBJECTIVES: This study investigated whether T1 mapping by cardiac magnetic resonance (CMR) reflects the clinical evolution of disease in myocarditis and supports its diagnosis independently of the disease stages. BACKGROUND: Acute viral myocarditis is characterized by a range of intracellular changes due to viral replication and extracellular spill of debris within days of viral infection. Convalescence may be characterized by a chronic low-grade inflammation leading to ventricular remodelling, but also a complete resolution of myocardial changes. METHODS: Patients with clinical diagnosis of viral myocarditis (N = 165) underwent routine clinical CMR protocol (1.5- and 3.0-T) for assessment of cardiac function and structure, and tissue characterization with T2-weighted imaging and late gadolinium enhancement. T1 mapping was obtained in a mid-ventricular short-axis slice before and >20 min after administration of 0.2 mmol/kg of gadobutrol. RESULTS: Compared with control subjects (n = 40), T1 indexes were increased in patients with myocarditis. Patients with acute symptoms (n = 61) had higher values of T1 indexes compared with patients in clinical convalescence (n = 67). Native T1 is an independent discriminator between health and disease, as well as a discriminator between acute and convalescent stage of the disease. Native T1- was superior to T2-weighted imaging and late gadolinium enhancement with high diagnostic accuracy and positive and negative predictive values. Using pre-defined cutoff values for normal ranges, we demonstrated that acute myocarditis can be independently identified by native T1 of >5 SD above the mean of normal range, whereas convalescence is best defined by either abnormal native T1 (>2 SD) or presence of late gadolinium enhancement. We prospectively tested a new diagnostic algorithm in an independent dataset of patients with clinical diagnosis of myocarditis and achieved similar diagnostic performance. CONCLUSIONS: The new diagnostic algorithm using native T1 can reliably discriminate between health and disease and determine the clinical disease stage in patients with a clinical diagnosis of myocarditis.

Maternal hemodynamics influence fetal hemodynamics in normal and hypertensive pregnancy.

OBJECTIVES: This observational case-control study aims to test whether there is a relationship between maternal systemic hemodynamics, maternal renin-angiotensin system and fetal hemodynamics in normal and hypertensive pregnancy. STUDY DESIGN: Four groups of non-pregnant women (n=18), pregnant controls (n=25), women with gestational hypertension (n=21) and preeclampsia (n=10) were included. MAIN OUTCOME MEASURES: Maternal echocardiography parameters, plasma renin and aldosterone were correlated with fetal Doppler parameters in third trimester pregnancy. RESULTS: Higher maternal mean arterial pressure and total peripheral vascular resistance were associated with lower fetal middle cerebral artery pulsatility index (PI) (r=-.51, p<0.01 and r=-.49, p<0.01, respectively); mean arterial pressure correlated negatively with ductus venosus PI (r=-.35, p=0.01); higher maternal plasma aldosterone levels were associated with lower maternal uterine artery resistance (r=-0.33, p=0.03). CONCLUSIONS: It seems that maternal hemodynamics influence fetal hemodynamics with protective adaptation in fetal cerebral and ductus venosus blood flow observed as maternal blood pressure and vascular resistance increase.

Four-dimensional image processing of myocardial CT perfusion for improved image quality and noise reduction.

BACKGROUND: Image noise and multiple sources of artifact may affect the accurate interpretation of myocardial CT perfusion (CTP) studies. Although artifact within the image is often time dependent, tissue characteristics remain unchanged irrespective of cardiac phase. OBJECTIVE: We assessed a new technique of 4-dimensional, spatiotemporal analysis, using redundant time domain information within additional phase acquisitions to reduce CTP image noise. METHODS: Four-dimensional analysis was assessed in a static phantom and in 10 CTP studies with invasive fractional flow reserve (FFR) correlation. For each voxel within the CTP study the distribution of local Hounsfield values was measured in both time and space with the use of a customized program within MATLAB software. These values were filtered to eliminate those likely to represent noise or rapidly changing beam hardening artifact. All CTP images were acquired within a single heartbeat with 320 detector-row CT. Image noise was quantified as the SD of voxel values within myocardial segments. Contrast was measured between normal and abnormal vascular territories as assessed by FFR. RESULTS: The mean image noise within the unprocessed CTP images was 30 HU (range, 23-42 HU). After 4-dimensional filtering the mean image noise was 22 HU (range, 15-29 HU). The mean reduction in image noise was 28% (P < 0.001). The mean contrast between normally perfused and ischemic segments was not significantly changed. The mean increase in contrast-to-noise ratio between ischemic territories and the myocardial average was 52% (P < 0.001). CONCLUSION: Four-dimensional analysis of CTP significantly reduces image noise and may assist in the assessment of myocardial perfusion studies.